从逆转Tau蛋白过度磷酸化探讨二异丙酚改善抑郁大鼠电休克后认知功能的神经心理学机制
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摘要
第一部分
不同电流和处置次数的电休克相应程度地调升嗅球切除抑郁模型大鼠海马内Glu的浓度
目的：观察不同电量和不同处置次数ECT干预对嗅球切除抑郁模型大鼠海马Glu浓度的影响。方法：建立大鼠嗅球切除抑郁模型，采用随机单位组3×3析因设计：将每只大鼠视为1个单位，予以2个处理因素，即电量（3水平：25mA、50mA、75mA）和处置次数（3水平：3次ECT、6次ECT、9次ECT）的所有组合。72只嗅球切除抑郁模型大鼠随机分为9个实验组（n=8）。全部ECT处置结束24h内留取海马，高效液相色谱法（High Performance LiquidChromatography，HPLC）检测Glu在海马中的含量。结果： ECT引发海马Glu浓度升高，ECT的电量和处置次数均可影响该过程，两者作用叠加。结论： ECT导致海马Glu浓度升高，从而加剧海马Tau蛋白的磷酸化程度。
第二部分
兴奋性氨基酸受体拮抗剂减轻电休克诱发的WKY大鼠认知障碍和Tau蛋白的过度磷酸化
目的：通过观察兴奋性氨基酸受体拮抗剂对ECT后WKY大鼠认知能力和Tau蛋白过度磷酸化的影响探讨兴奋性氨基酸受体拮抗剂对Tau蛋白过度磷酸化的调节及两者对抑郁大鼠认知能力的影响。方法：采用随机单位组析因设计：将每只大鼠视为1个单位，予2个处理因素，即ECT处置与否（2水平：无处置、施行一个疗程ECT）和兴奋性氨基酸受体拮抗剂使用与否（3水平：注射生理盐水、MK-801、DNQX）的所有组合。72只WKY大鼠随机分为6个实验组（n=8）。全部ECT处置结束24h内开始Morris水迷宫（Morris water maze，MWwM）检测认知能力，后留取海马。HPLC法检测Glu在海马中的含量；免疫组织化学（immunohistochemistry， IHC-SP）法和Western-lotting法检测Tau5（总Tau蛋白）、 p-PHF1Ser396/404、p-AT8Ser199/202、p-12E8Ser262在海马中的表达。结果：ECT和GluR拮抗剂均可造成大鼠认知障碍，即延长逃避潜伏期（escape latency，EL）并缩短空间探索时间（space exploration time，SET）；两者的影响呈相减效果，即ECT和Glu受体拮抗剂合用之后，其造成的大鼠认知障碍程度反而减轻。ECT可明显增加海马中Glu的浓度；GluR拮抗剂对海马中Glu的浓度没有明确影响。ECT和GluR拮抗剂对海马总Tau蛋白表达无明确影响。ECT可增加海马中磷酸化Tau蛋白的表达；GluR拮抗剂可减少海马中磷酸化Tau蛋白的表达；两者的影响呈相减效果，即GluR拮抗剂可使ECT造成的海马中磷酸化Tau蛋白的表达增加的幅度减缓。结论： NMDAR和AMPAR拮抗剂可以阻止“ECT导致海马Glu浓度升高，从而加剧海马Tau蛋白的磷酸化程度”这一过程，且两者效果相似；其具体机制与阻断兴奋性毒性有关。
第三部分
二异丙酚逆转嗅球切除抑郁模型大鼠电休克后的Tau蛋白过度磷酸化和认知障碍
目的：通过观察二异丙酚对ECT后嗅球切除抑郁模型大鼠认知能力和Tau蛋白过度磷酸化的影响探讨兴奋性氨基酸受体拮抗剂对Tau蛋白过度磷酸化的调节及两者对抑郁大鼠认知能力的影响。方法：按随机单位组2×2析因设计设置2个干预因素，即ECT干预（2水平：无处置、施行一个疗程ECT）和二异丙酚干预（2水平：腹腔注射5ml生理盐水或5ml二异丙酚100mg/kg）的所有组合。选24W健康雄性Sprague-Dawley大鼠建立嗅球切除抑郁模型，将32只24W龄模型大鼠随机分为4个实验组（n=8）：I组（腹腔注射5ml二异丙酚100mg/kg）、II组（腹腔注射5ml二异丙酚100mg/kg+施行ECT1个疗程）、III组（腹腔注射5ml生理盐水）、IV组（腹腔注射5ml生理盐水+施行ECT1个疗程）。全部ECT处置结束24h内开始Morris水迷宫检测，之后留取海马组织.高效液相色谱法检测神经递质Glu在海马组织中的含量；免疫组化SP法和Western blotting法检测Tau-5（总Tau蛋白）、p-PHF1Ser396/404、p-AT8Ser199/202、p-12E8Ser262、GSK-3β1H8和PP-2A在海马组织神经元中的表达。结果：ECT和二异丙酚均可造成大鼠认知障碍，即延长EL并缩短SET；两者的影响呈相减效果。ECT可明显增加海马中神经递质Glu的浓度；二异丙酚可降低海马中神经递质Glu的浓度，且两者有相减效果。ECT和二异丙酚对海马总Tau蛋白和PP-2A蛋白的表达无明显影响。ECT可增加海马中磷酸化Tau蛋白和GSK-3β1H8蛋白的表达；二异丙酚可减少海马中磷酸化Tau蛋白和GSK-3β1H8蛋白的表达；两者的影响均呈相减效果。结论：ECT导致海马Glu浓度升高，通过上调GSK-3β1H8增加海马Tau蛋白的磷酸化程度导致认知功能障碍，而二异丙酚则可通过降低海马Glu浓度下调GSK-3β1H8的表达，从而减缓Tau蛋白的磷酸化程度以改善ECT后的认知功能。
第四部分
二异丙酚与NMDAR拮抗剂逆转嗅球切除抑郁模型大鼠电休克后认知障碍的神经心理学机制之比较
目的：通过观察二异丙酚和对ECT后嗅球切除抑郁模型大鼠空间认知能力和Tau蛋白过度磷酸化的影响，探讨两者对Tau蛋白过度磷酸化的调节及两者对抑郁大鼠空间认知能力的影响，并比较其效果和作用途径，以期为改善认知障碍的神经心理学机制研究和临床干预性治疗提供实验依据。方法：采用随机单位组2×3析因设计：将每只大鼠视为1个单位，予以2个处理因素，即ECT（2水平：无处置、施行1疗程ECT）和药物（3水平：腹腔注射生理盐水、NMDAR拮抗剂MK-801、二异丙酚）的所有组合。48只嗅球切除抑郁模型大鼠随机分为6个实验组（n=8）。全部ECT结束24h内开始MWM检测，留取海马，HPLC法检测Glu在海马中的含量，IHC-SP法和Western-lotting法检测p-AT8Ser202和GSK-3β1H8在海马中的表达。结果：二异丙酚、NMDAR拮抗剂及ECT均可造成大鼠认知障碍，即延长EL并缩短SET；前两者效果相似且和ECT的影响呈相减效果。ECT可明显增加海马中Glu的浓度；二异丙酚可降低海马中Glu的浓度，且两者有相减效果；而NMDAR拮抗剂对海马中Glu的浓度无明显影响。ECT可增加海马中p-AT8Ser202及促进其磷酸化的GSK-3β1H8的表达；二异丙酚和NMDAR拮抗剂可减缓海马中p-AT8Ser202及促进其磷酸化的GSK-3β1H8表达上调；两者效果相似且和ECT的影响呈相减效果。结论：二异丙酚则可通过降低海马Glu浓度减缓Tau蛋白的磷酸化，从而改善大鼠ECT后的认知能力；GSK-3β是该信号通路的关键蛋白；二异丙酚改善电休克后的认知能力的效果优于NMDAR拮抗剂。
第五部分
二异丙酚、人参皂苷Rg-1和氯化锂逆转电休克后嗅球切除抑郁大鼠认知障碍的神经心理学机制之比较
目的：观察二异丙酚与人参皂苷Rg-1和LiCl对ECT后嗅球切除抑郁模型大鼠认知能力、海马内Glu浓度和Tau蛋白磷酸化的影响，比较其药理机制，为临床治疗方案的制定提供新的理论依据和思路。方法：按随机单位组2×4析因设计，即ECT干预（2水平：无处置、施行1疗程ECT）和药物干预（4水平：海马CA1区微量注射二异丙酚、人参皂苷Rg-1、LiCl，20μg1μL-1）的所有组合。64只嗅球切除抑郁模型大鼠随机分为8个实验组（n=8）。全部ECT处置结束后开始MWM测试，取海马通过HPLC法检测Glu的含量。Western-blotting法检测Tau-5和p-AT8Ser202在海马中的表达。结果：二异丙酚和ECT造成认知障碍，而与ECT合用则会缓解ECT后的认知障碍；人参皂苷Rg-1和LiCl可改善ECT后的认知能力；ECT可明显增加海马中Glu浓度、二异丙酚和人参皂苷Rg-1在ECT前后均可减少Glu浓度；二异丙酚与人参皂苷Rg-1和LiCl可使ECT造成的海马中磷酸化Tau蛋白的表达增加的幅度减缓。结论：二异丙酚与人参皂苷Rg-1和LiCl均可缓解ECT后Tau蛋白过度磷酸化程度进而改善ECT后的认知能力；前两者与降低海马中Glu浓度有关。
全文结论
1ECT导致海马Glu浓度升高，Glu激动NMDAR和AMPAR，从而通过上调GSK-3β1H8增加海马Tau蛋白的磷酸化程度，从而导致认知障碍。
2GluR拮抗剂、二异丙酚、人参皂苷Rg-1亦通过降低海马Glu浓度下调GSK-3β1H8的表达，从而减缓Tau蛋白的磷酸化程度以改善ECT后的认知能力；氯化锂缓解ECT后的Tau蛋白过度磷酸化与Glu无关。
3人参皂苷Rg-1和氯化锂改善ECT后的认知能力的效果优于二异丙酚；二异丙酚改善ECT后认知能力的效果优于NMDAR拮抗剂；NMDAR拮抗剂与AMPAR拮抗剂改善ECT后的认知能力的效果相似。
Protein Tau is a very unequal phosphoric microtubule associatedprotein, which affect the transport of substances in the axons of the neurons,whose phosphorylation is one of the key methods to regulate neuronalfunction. The hyperphosphorylation of protein Tau can damage thelearning and memory of rats. The impairment of learning-memory inducedby electroconvulsive shock in depressed rats is relevant to the functionfailure of glutamic acid signal system. The rise of glutamate which inducedby electroconvulsive shock in depressed rats can lead to the impairment oflearning-memory through up-regulate the hyperphosphorylation of proteinTau? Is this process related to the excitotoxicty of glutamate? Can theexcitatory amino acids receptor antagonists and propofolwhich play a roleas GluR antagonist inhibit this process? What are the similarities anddifferences about the effects and the neuropsychology mechanisms ofpropofol, ginsenoside Rg-1and lithium protects against the impairment oflearning-memory induced by electroconvulsive shock in depressed rats?The series of problems above attracted strong interest of researchers.Therefore, we engaged in this research in order to explore the mechanismof this process.
PART Ⅰ
The electroconvulsive shock of different electric quantity and ofdifferent treatment number up-regulated the content of glutamate inthe hippocampus of the depression model rats whose olfactory bulbswere removed
Objective This study explore the effect of the electroconvulsive shockof different electric current and different duration up-regulated the contentof glutamate in the hippocampus of depressed rats. Methods Thedepression model rats whose olfactory bulbs were removed wereestablished. As the analysis of variance of factorial design set up twointervention factors which are the electric quantity factor(three levels:25mA,50mA,75mA) and the treatment number factor(three level:3timeselectroconvulsive shock,3times electroconvulsive shock,9timeselectroconvulsive shock). Seventy-two adult depression model rats whoseolfactory bulbs were removed were randomly divided into six experimentalgroups (n=6, in each group). The hippocampus was removed within24hours after the course of electroconvulsive shock finished. Results Theelectroconvulsive shock can significantly up-regulated the content ofglutamate. The changes were correlated with the electric quantity and thetreatment number of the electroconvulsive shock. And both influencespresent additive effect. Conclusions Our results indicate that theelectroconvulsive shock up-regulated the content of glutamate in thehippocampus of rats.
PART Ⅱ
MK-801or CNQX reduces electroconvulsive shock-inducedimpairment of learning-memory and hyperphosphorylation of tau inWYK rats with depression-like behaviors
Objective This study explore the reversion of the excitatory aminoacid receptor antagonists against the impairment of learning-memory andthe hyperphosphorylation of Protein Tau induced by electroconvulsiveshock in depressed rats. Methods As the analysis of variance of factorialdesign set up two intervention factors which are the electroconvulsiveshock (two levels: no disposition; A course of electroconvulsive shock) andthe excitatory amino acid receptor antagonists (three levels: iv Saline; ivNMDA receptor antagonist MK-801; iv AMPA receptor antagonistDNQX). Fourty-eight adult WYK rats were randomly divided into sixexperimental groups (n=8, in each group). The Morris water maze teststarted within1day after the course of electroconvulsive shock finished inorder to evaluate learning-memory. The hippocampus was removed fromrats within1day after the morris water maze test finished. Detect of thecontent of glutamate in the hippocampus of rats by High PerformanceLiquid Chromatography. Detect of the content of Protein Tau whichincludes Tau5(total protein Tau), p-PHF1Ser396/404, p-AT8Ser199/202,p-12E8Ser262in the hippocampus of rats with the methods ofimmunohistochemistry staining (SP) and Western blotting test. ResultsThe electroconvulsive shock and the glutamate ionic receptor blockers caninduce the impairment of learning-memory in depressed rats, extending theevasive latency time and shorten the space exploration time. And bothinfluences present subtract effect. The electroconvulsive shock cansignificantly up-regulated the content of glutamate in the hippocampus ofdepressed rats which was not affected by the glutamate ionic receptorblockers. The electroconvulsive shock and the glutamate ionic receptorblockers do not affect the total protein Tau in the hippocampus of rats. Theelectroconvulsive shock can up-regulated the hyperphosphorylation ofprotein Tau in the hippocampus of depressed rats which is can be reduced by the glutamate ionic receptor blockers. And both influences presentsubtract effect. Conclusions Our results indicate that the electroconvulsiveshock up-regulated the content of glutamate in the hippocampus ofdepressed rats, which up-regulated the hyperphosphorylation of protein Tauwhich can induce the impairment of learning-memory in depressed rats.
PART Ⅲ
Propofol protects against the impairment of learning-memory andreduces the hyperphosphorylation of protein Tau induced byelectroconvulsive shock in the depression model rats whose olfactorybulbs were removed
Objective This study explore the reversion of the propofol against theimpairment of learning-memory and the hyperphosphorylation of proteinTau induced by electroconvulsive shock in depressed rats. Methods As theanalysis of variance of factorial design set up two intervention factorswhich are the electroconvulsive shock (two levels: no disposition; A courseof electroconvulsive shock) and the propofol (two levels:5ml Saline wasinjected peritoneally;5ml propofol was injected peritoneally by dosage of100mg/kg). Thirty-two the adult depression model rats whose olfactorybulbs were removed were randomly divided into four experimental groups(n=8, in each group). The Morris water maze test started within1day afterthe course of electroconvulsive shock finished in order to evaluatelearning-memory. The hippocampus was removed from rats within1dayafter the Morris water maze test finished. Detect of the content of glutamatein the hippocampus of rats by High Performance Liquid Chromatography.Detect of the content of Protein Tau which includes Tau-5(Total proteinTau), p-PHF1Ser396/404, p-AT8Ser199/202, p-12E8Ser262, GSK-3β1H8and PP-2Ain the hippocampus of rats with the methods of Western blotting test.Results The electroconvulsive shock and the propofol can induce the impairment of learning-memory in depressed rats, extending the evasivelatency time and shortening the space exploration time. And bothinfluences present subtract effect. The electroconvulsive shock cansignificantly up-regulated the content of glutamate in the hippocampus ofdepressed rats which was reduces by the propofol. And both influencespresent subtract effect. The electroconvulsive shock and the propofol doesnot affect the total protein Tau and protein PP-2A in the hippocampus ofrats. The electroconvulsive shock can up-regulated thehyperphosphorylation of protein Tau and the expression of GSK-3β1H8inthe hippocampus of depressed rats which is can be reduced by the propofol.And both influences present subtract effect. Conclusions Our resultsindicate that the electroconvulsive shock up-regulated the content ofglutamate in the hippocampus of depressed rats, which up-regulated thehyperphosphorylation of protein Tau through up-regulating the expressionof GSK-3β1H8, which can induce the impairment of learning-memory indepressed rats; and the propofol protects against the impairment oflearning-memory and reduce the hyperphosphorylation of protein Tauinduced by electroconvulsive shock in depressed rats through reducing theexpression of GSK-3β1H8and the content of glutamate in the hippocampus.
PART Ⅳ
Comparison of the neuropsychology mechanisms of propofol andNMDA receptor antagonist protects against the impairment oflearning-memory induced by electroconvulsive shock in depressed rats
Objective This study explore the reversion of propofol and NMDAreceptor antagonist against the impairment of learning-memory and thehyperphosphorylation of protein Tau induced by electroconvulsive shock indepressed rats. Methods As the analysis of variance of factorial design setup two intervention factors which are the electroconvulsive shock (two levels: no disposition; a course of electroconvulsive shock) and the drugs(three levels: ip Saline; ip propofol; ip MK-801). Forty-eight adultdepression model rats whose olfactory bulbs were removed were randomlydivided into six experimental groups (n=8, in each group). The Morriswater maze test started within1day after the course of electroconvulsiveshock finished in order to evaluate learning-memory. The hippocampuswas removed from rats within1day after the Morris water maze testfinished. Detect of the content of glutamate in the hippocampus of rats byHigh Performance Liquid Chromatography. Detect of the expression ofprotein Tau which includes p-AT8Ser202and GSK-3β1H8in the hippocampusof rats with the methods of immunohistochemistry staining (SP) andWestern blotting test. Results The drugs (propofol and MK-801) and theelectroconvulsive shock can induce the impairment of learning-memory indepressed rats, extending the evasive latency time and shorten the spaceexploration time. And both influences present subtract effect. Theelectroconvulsive shock can significantly up-regulated the content ofglutamate, which was not affected by MK-801, in the hippocampus ofdepressed rats which was reduces by the propofol. And both influencespresent subtract effects. The electroconvulsive shock and the drugs do notaffect the total protein Tau in the hippocampus of rats. Theelectroconvulsive shock can up-regulated the hyperphosphorylation ofprotein Tau in the hippocampus of depressed rats which is can be reducedby propofol and MK-801. And the influences between theelectroconvulsive shock and the drugs present subtract effects. Our resultsindicate that the electroconvulsive shock up-regulated the content ofglutamate in the hippocampus of depressed rats, which up-regulated thehyperphosphorylation of protein Tau which can induce the impairment oflearning-memory in depressed rats; and propofol protects against the impairment of learning-memory and reduce the hyperphosphorylation ofprotein Tau induced by electroconvulsive shock in depressed rats. GSK-3βis the key protein in this signaling pathway. Conclusions Our resultsindicate that the electroconvulsive shock reduce the impairment oflearning-memory the hyperphosphorylation of protein Tau in depressed ratsthough up-regulated the content of glutamate.
PART Ⅴ
Comparison of the neuropsychology mechanisms of propofol,ginsenoside Rg-1and lithium protects against the impairment oflearning-memory induced by electroconvulsive shock in depressed rats
Objective This study explore the reversion of propofol, ginsenosideRg-1, lithium against the impairment of learning-memory and thehyperphosphorylation of protein Tau induced by electroconvulsive shockand the concentration of glutamic acid in the hippocampus in depressed rats.Methods As the analysis of variance of factorial design set up twointervention factors which are the electroconvulsive shock groups (twolevels: no disposition; A course of electroconvulsive shock) and the drugintervention groups (four levels: Microinjection of propofol, ginsenosideRg-1and lithium,20μg1μl-1). Sixty-four adult depression model rats whoseolfactory bulbs were removed were randomly divided into eightexperimental groups (n=8, in each group). The Morris water maze teststarted within1day after the course of electroconvulsive shock finished inorder to evaluate learning-memory. Detect of the content of glutamate inthe hippocampus of rats by High Performance Liquid Chromatography.Detect of the content of protein Tau which includes Tau-5and p-AT8Ser202in the hippocampus of rats with the methods of Western blotting test.Results Propofol and the electroconvulsive shock can induce theimpairment of learning-memory in depressed rats. Ginsenoside Rg-1and lithium can protects against the impairment of learning-memory induced byelectroconvulsive shock in depressed rats. The electroconvulsive shock cansignificantly up-regulated the content of glutamate, which was reduces bypropofol. The electroconvulsive shock can up-regulated thehyperphosphorylation of protein Tau in the hippocampus of depressed ratswhich is can be reduced by these three medicines. Conclusions Our resultsindicate that propofol, ginsenoside Rg-1and lithium protects against theimpairment of learning-memory induced by electroconvulsive shock indepressed rats though reducing the hyperphosphorylation of protein Tau.The first two is not content with the glutamate in the hippocampus, withwhich lithium is not content.
CONCLUSIONS OF THE TATOL PAPER
Our results indicate that the electroconvulsive shock up-regulated thecontent of glutamate in the hippocampus of depressed rats, whichup-regulated the hyperphosphorylation of protein Tau throughup-regulating the expression of GSK-3β1H8, which can induce theimpairment of learning-memory in depressed rats. Propofol protects againstthe impairment of learning-memory and reduce the hyperphosphorylationof protein Tau induced by electroconvulsive shock in depressed ratsthrough reducing the expression of GSK-3β1H8and the content of glutamatein the hippocampus. GluR antagonists, ginsenoside Rg-1and lithiumprotects against the impairment of learning-memory induced byelectroconvulsive shock in depressed rats though reducing thehyperphosphorylation of protein Tau, too.
不同电流和处置次数的电休克相应程度地调升嗅球切除抑郁模型大鼠海马内Glu的浓度
目的：观察不同电量和不同处置次数ECT干预对嗅球切除抑郁模型大鼠海马Glu浓度的影响。方法：建立大鼠嗅球切除抑郁模型，采用随机单位组3×3析因设计：将每只大鼠视为1个单位，予以2个处理因素，即电量（3水平：25mA、50mA、75mA）和处置次数（3水平：3次ECT、6次ECT、9次ECT）的所有组合。72只嗅球切除抑郁模型大鼠随机分为9个实验组（n=8）。全部ECT处置结束24h内留取海马，高效液相色谱法（High Performance LiquidChromatography，HPLC）检测Glu在海马中的含量。结果： ECT引发海马Glu浓度升高，ECT的电量和处置次数均可影响该过程，两者作用叠加。结论： ECT导致海马Glu浓度升高，从而加剧海马Tau蛋白的磷酸化程度。
第二部分
兴奋性氨基酸受体拮抗剂减轻电休克诱发的WKY大鼠认知障碍和Tau蛋白的过度磷酸化
目的：通过观察兴奋性氨基酸受体拮抗剂对ECT后WKY大鼠认知能力和Tau蛋白过度磷酸化的影响探讨兴奋性氨基酸受体拮抗剂对Tau蛋白过度磷酸化的调节及两者对抑郁大鼠认知能力的影响。方法：采用随机单位组析因设计：将每只大鼠视为1个单位，予2个处理因素，即ECT处置与否（2水平：无处置、施行一个疗程ECT）和兴奋性氨基酸受体拮抗剂使用与否（3水平：注射生理盐水、MK-801、DNQX）的所有组合。72只WKY大鼠随机分为6个实验组（n=8）。全部ECT处置结束24h内开始Morris水迷宫（Morris water maze，MWwM）检测认知能力，后留取海马。HPLC法检测Glu在海马中的含量；免疫组织化学（immunohistochemistry， IHC-SP）法和Western-lotting法检测Tau5（总Tau蛋白）、 p-PHF1Ser396/404、p-AT8Ser199/202、p-12E8Ser262在海马中的表达。结果：ECT和GluR拮抗剂均可造成大鼠认知障碍，即延长逃避潜伏期（escape latency，EL）并缩短空间探索时间（space exploration time，SET）；两者的影响呈相减效果，即ECT和Glu受体拮抗剂合用之后，其造成的大鼠认知障碍程度反而减轻。ECT可明显增加海马中Glu的浓度；GluR拮抗剂对海马中Glu的浓度没有明确影响。ECT和GluR拮抗剂对海马总Tau蛋白表达无明确影响。ECT可增加海马中磷酸化Tau蛋白的表达；GluR拮抗剂可减少海马中磷酸化Tau蛋白的表达；两者的影响呈相减效果，即GluR拮抗剂可使ECT造成的海马中磷酸化Tau蛋白的表达增加的幅度减缓。结论： NMDAR和AMPAR拮抗剂可以阻止“ECT导致海马Glu浓度升高，从而加剧海马Tau蛋白的磷酸化程度”这一过程，且两者效果相似；其具体机制与阻断兴奋性毒性有关。
第三部分
二异丙酚逆转嗅球切除抑郁模型大鼠电休克后的Tau蛋白过度磷酸化和认知障碍
目的：通过观察二异丙酚对ECT后嗅球切除抑郁模型大鼠认知能力和Tau蛋白过度磷酸化的影响探讨兴奋性氨基酸受体拮抗剂对Tau蛋白过度磷酸化的调节及两者对抑郁大鼠认知能力的影响。方法：按随机单位组2×2析因设计设置2个干预因素，即ECT干预（2水平：无处置、施行一个疗程ECT）和二异丙酚干预（2水平：腹腔注射5ml生理盐水或5ml二异丙酚100mg/kg）的所有组合。选24W健康雄性Sprague-Dawley大鼠建立嗅球切除抑郁模型，将32只24W龄模型大鼠随机分为4个实验组（n=8）：I组（腹腔注射5ml二异丙酚100mg/kg）、II组（腹腔注射5ml二异丙酚100mg/kg+施行ECT1个疗程）、III组（腹腔注射5ml生理盐水）、IV组（腹腔注射5ml生理盐水+施行ECT1个疗程）。全部ECT处置结束24h内开始Morris水迷宫检测，之后留取海马组织.高效液相色谱法检测神经递质Glu在海马组织中的含量；免疫组化SP法和Western blotting法检测Tau-5（总Tau蛋白）、p-PHF1Ser396/404、p-AT8Ser199/202、p-12E8Ser262、GSK-3β1H8和PP-2A在海马组织神经元中的表达。结果：ECT和二异丙酚均可造成大鼠认知障碍，即延长EL并缩短SET；两者的影响呈相减效果。ECT可明显增加海马中神经递质Glu的浓度；二异丙酚可降低海马中神经递质Glu的浓度，且两者有相减效果。ECT和二异丙酚对海马总Tau蛋白和PP-2A蛋白的表达无明显影响。ECT可增加海马中磷酸化Tau蛋白和GSK-3β1H8蛋白的表达；二异丙酚可减少海马中磷酸化Tau蛋白和GSK-3β1H8蛋白的表达；两者的影响均呈相减效果。结论：ECT导致海马Glu浓度升高，通过上调GSK-3β1H8增加海马Tau蛋白的磷酸化程度导致认知功能障碍，而二异丙酚则可通过降低海马Glu浓度下调GSK-3β1H8的表达，从而减缓Tau蛋白的磷酸化程度以改善ECT后的认知功能。
第四部分
二异丙酚与NMDAR拮抗剂逆转嗅球切除抑郁模型大鼠电休克后认知障碍的神经心理学机制之比较
目的：通过观察二异丙酚和对ECT后嗅球切除抑郁模型大鼠空间认知能力和Tau蛋白过度磷酸化的影响，探讨两者对Tau蛋白过度磷酸化的调节及两者对抑郁大鼠空间认知能力的影响，并比较其效果和作用途径，以期为改善认知障碍的神经心理学机制研究和临床干预性治疗提供实验依据。方法：采用随机单位组2×3析因设计：将每只大鼠视为1个单位，予以2个处理因素，即ECT（2水平：无处置、施行1疗程ECT）和药物（3水平：腹腔注射生理盐水、NMDAR拮抗剂MK-801、二异丙酚）的所有组合。48只嗅球切除抑郁模型大鼠随机分为6个实验组（n=8）。全部ECT结束24h内开始MWM检测，留取海马，HPLC法检测Glu在海马中的含量，IHC-SP法和Western-lotting法检测p-AT8Ser202和GSK-3β1H8在海马中的表达。结果：二异丙酚、NMDAR拮抗剂及ECT均可造成大鼠认知障碍，即延长EL并缩短SET；前两者效果相似且和ECT的影响呈相减效果。ECT可明显增加海马中Glu的浓度；二异丙酚可降低海马中Glu的浓度，且两者有相减效果；而NMDAR拮抗剂对海马中Glu的浓度无明显影响。ECT可增加海马中p-AT8Ser202及促进其磷酸化的GSK-3β1H8的表达；二异丙酚和NMDAR拮抗剂可减缓海马中p-AT8Ser202及促进其磷酸化的GSK-3β1H8表达上调；两者效果相似且和ECT的影响呈相减效果。结论：二异丙酚则可通过降低海马Glu浓度减缓Tau蛋白的磷酸化，从而改善大鼠ECT后的认知能力；GSK-3β是该信号通路的关键蛋白；二异丙酚改善电休克后的认知能力的效果优于NMDAR拮抗剂。
第五部分
二异丙酚、人参皂苷Rg-1和氯化锂逆转电休克后嗅球切除抑郁大鼠认知障碍的神经心理学机制之比较
目的：观察二异丙酚与人参皂苷Rg-1和LiCl对ECT后嗅球切除抑郁模型大鼠认知能力、海马内Glu浓度和Tau蛋白磷酸化的影响，比较其药理机制，为临床治疗方案的制定提供新的理论依据和思路。方法：按随机单位组2×4析因设计，即ECT干预（2水平：无处置、施行1疗程ECT）和药物干预（4水平：海马CA1区微量注射二异丙酚、人参皂苷Rg-1、LiCl，20μg1μL-1）的所有组合。64只嗅球切除抑郁模型大鼠随机分为8个实验组（n=8）。全部ECT处置结束后开始MWM测试，取海马通过HPLC法检测Glu的含量。Western-blotting法检测Tau-5和p-AT8Ser202在海马中的表达。结果：二异丙酚和ECT造成认知障碍，而与ECT合用则会缓解ECT后的认知障碍；人参皂苷Rg-1和LiCl可改善ECT后的认知能力；ECT可明显增加海马中Glu浓度、二异丙酚和人参皂苷Rg-1在ECT前后均可减少Glu浓度；二异丙酚与人参皂苷Rg-1和LiCl可使ECT造成的海马中磷酸化Tau蛋白的表达增加的幅度减缓。结论：二异丙酚与人参皂苷Rg-1和LiCl均可缓解ECT后Tau蛋白过度磷酸化程度进而改善ECT后的认知能力；前两者与降低海马中Glu浓度有关。
全文结论
1ECT导致海马Glu浓度升高，Glu激动NMDAR和AMPAR，从而通过上调GSK-3β1H8增加海马Tau蛋白的磷酸化程度，从而导致认知障碍。
2GluR拮抗剂、二异丙酚、人参皂苷Rg-1亦通过降低海马Glu浓度下调GSK-3β1H8的表达，从而减缓Tau蛋白的磷酸化程度以改善ECT后的认知能力；氯化锂缓解ECT后的Tau蛋白过度磷酸化与Glu无关。
3人参皂苷Rg-1和氯化锂改善ECT后的认知能力的效果优于二异丙酚；二异丙酚改善ECT后认知能力的效果优于NMDAR拮抗剂；NMDAR拮抗剂与AMPAR拮抗剂改善ECT后的认知能力的效果相似。
Protein Tau is a very unequal phosphoric microtubule associatedprotein, which affect the transport of substances in the axons of the neurons,whose phosphorylation is one of the key methods to regulate neuronalfunction. The hyperphosphorylation of protein Tau can damage thelearning and memory of rats. The impairment of learning-memory inducedby electroconvulsive shock in depressed rats is relevant to the functionfailure of glutamic acid signal system. The rise of glutamate which inducedby electroconvulsive shock in depressed rats can lead to the impairment oflearning-memory through up-regulate the hyperphosphorylation of proteinTau? Is this process related to the excitotoxicty of glutamate? Can theexcitatory amino acids receptor antagonists and propofolwhich play a roleas GluR antagonist inhibit this process? What are the similarities anddifferences about the effects and the neuropsychology mechanisms ofpropofol, ginsenoside Rg-1and lithium protects against the impairment oflearning-memory induced by electroconvulsive shock in depressed rats?The series of problems above attracted strong interest of researchers.Therefore, we engaged in this research in order to explore the mechanismof this process.
PART Ⅰ
The electroconvulsive shock of different electric quantity and ofdifferent treatment number up-regulated the content of glutamate inthe hippocampus of the depression model rats whose olfactory bulbswere removed
Objective This study explore the effect of the electroconvulsive shockof different electric current and different duration up-regulated the contentof glutamate in the hippocampus of depressed rats. Methods Thedepression model rats whose olfactory bulbs were removed wereestablished. As the analysis of variance of factorial design set up twointervention factors which are the electric quantity factor(three levels:25mA,50mA,75mA) and the treatment number factor(three level:3timeselectroconvulsive shock,3times electroconvulsive shock,9timeselectroconvulsive shock). Seventy-two adult depression model rats whoseolfactory bulbs were removed were randomly divided into six experimentalgroups (n=6, in each group). The hippocampus was removed within24hours after the course of electroconvulsive shock finished. Results Theelectroconvulsive shock can significantly up-regulated the content ofglutamate. The changes were correlated with the electric quantity and thetreatment number of the electroconvulsive shock. And both influencespresent additive effect. Conclusions Our results indicate that theelectroconvulsive shock up-regulated the content of glutamate in thehippocampus of rats.
PART Ⅱ
MK-801or CNQX reduces electroconvulsive shock-inducedimpairment of learning-memory and hyperphosphorylation of tau inWYK rats with depression-like behaviors
Objective This study explore the reversion of the excitatory aminoacid receptor antagonists against the impairment of learning-memory andthe hyperphosphorylation of Protein Tau induced by electroconvulsiveshock in depressed rats. Methods As the analysis of variance of factorialdesign set up two intervention factors which are the electroconvulsiveshock (two levels: no disposition; A course of electroconvulsive shock) andthe excitatory amino acid receptor antagonists (three levels: iv Saline; ivNMDA receptor antagonist MK-801; iv AMPA receptor antagonistDNQX). Fourty-eight adult WYK rats were randomly divided into sixexperimental groups (n=8, in each group). The Morris water maze teststarted within1day after the course of electroconvulsive shock finished inorder to evaluate learning-memory. The hippocampus was removed fromrats within1day after the morris water maze test finished. Detect of thecontent of glutamate in the hippocampus of rats by High PerformanceLiquid Chromatography. Detect of the content of Protein Tau whichincludes Tau5(total protein Tau), p-PHF1Ser396/404, p-AT8Ser199/202,p-12E8Ser262in the hippocampus of rats with the methods ofimmunohistochemistry staining (SP) and Western blotting test. ResultsThe electroconvulsive shock and the glutamate ionic receptor blockers caninduce the impairment of learning-memory in depressed rats, extending theevasive latency time and shorten the space exploration time. And bothinfluences present subtract effect. The electroconvulsive shock cansignificantly up-regulated the content of glutamate in the hippocampus ofdepressed rats which was not affected by the glutamate ionic receptorblockers. The electroconvulsive shock and the glutamate ionic receptorblockers do not affect the total protein Tau in the hippocampus of rats. Theelectroconvulsive shock can up-regulated the hyperphosphorylation ofprotein Tau in the hippocampus of depressed rats which is can be reduced by the glutamate ionic receptor blockers. And both influences presentsubtract effect. Conclusions Our results indicate that the electroconvulsiveshock up-regulated the content of glutamate in the hippocampus ofdepressed rats, which up-regulated the hyperphosphorylation of protein Tauwhich can induce the impairment of learning-memory in depressed rats.
PART Ⅲ
Propofol protects against the impairment of learning-memory andreduces the hyperphosphorylation of protein Tau induced byelectroconvulsive shock in the depression model rats whose olfactorybulbs were removed
Objective This study explore the reversion of the propofol against theimpairment of learning-memory and the hyperphosphorylation of proteinTau induced by electroconvulsive shock in depressed rats. Methods As theanalysis of variance of factorial design set up two intervention factorswhich are the electroconvulsive shock (two levels: no disposition; A courseof electroconvulsive shock) and the propofol (two levels:5ml Saline wasinjected peritoneally;5ml propofol was injected peritoneally by dosage of100mg/kg). Thirty-two the adult depression model rats whose olfactorybulbs were removed were randomly divided into four experimental groups(n=8, in each group). The Morris water maze test started within1day afterthe course of electroconvulsive shock finished in order to evaluatelearning-memory. The hippocampus was removed from rats within1dayafter the Morris water maze test finished. Detect of the content of glutamatein the hippocampus of rats by High Performance Liquid Chromatography.Detect of the content of Protein Tau which includes Tau-5(Total proteinTau), p-PHF1Ser396/404, p-AT8Ser199/202, p-12E8Ser262, GSK-3β1H8and PP-2Ain the hippocampus of rats with the methods of Western blotting test.Results The electroconvulsive shock and the propofol can induce the impairment of learning-memory in depressed rats, extending the evasivelatency time and shortening the space exploration time. And bothinfluences present subtract effect. The electroconvulsive shock cansignificantly up-regulated the content of glutamate in the hippocampus ofdepressed rats which was reduces by the propofol. And both influencespresent subtract effect. The electroconvulsive shock and the propofol doesnot affect the total protein Tau and protein PP-2A in the hippocampus ofrats. The electroconvulsive shock can up-regulated thehyperphosphorylation of protein Tau and the expression of GSK-3β1H8inthe hippocampus of depressed rats which is can be reduced by the propofol.And both influences present subtract effect. Conclusions Our resultsindicate that the electroconvulsive shock up-regulated the content ofglutamate in the hippocampus of depressed rats, which up-regulated thehyperphosphorylation of protein Tau through up-regulating the expressionof GSK-3β1H8, which can induce the impairment of learning-memory indepressed rats; and the propofol protects against the impairment oflearning-memory and reduce the hyperphosphorylation of protein Tauinduced by electroconvulsive shock in depressed rats through reducing theexpression of GSK-3β1H8and the content of glutamate in the hippocampus.
PART Ⅳ
Comparison of the neuropsychology mechanisms of propofol andNMDA receptor antagonist protects against the impairment oflearning-memory induced by electroconvulsive shock in depressed rats
Objective This study explore the reversion of propofol and NMDAreceptor antagonist against the impairment of learning-memory and thehyperphosphorylation of protein Tau induced by electroconvulsive shock indepressed rats. Methods As the analysis of variance of factorial design setup two intervention factors which are the electroconvulsive shock (two levels: no disposition; a course of electroconvulsive shock) and the drugs(three levels: ip Saline; ip propofol; ip MK-801). Forty-eight adultdepression model rats whose olfactory bulbs were removed were randomlydivided into six experimental groups (n=8, in each group). The Morriswater maze test started within1day after the course of electroconvulsiveshock finished in order to evaluate learning-memory. The hippocampuswas removed from rats within1day after the Morris water maze testfinished. Detect of the content of glutamate in the hippocampus of rats byHigh Performance Liquid Chromatography. Detect of the expression ofprotein Tau which includes p-AT8Ser202and GSK-3β1H8in the hippocampusof rats with the methods of immunohistochemistry staining (SP) andWestern blotting test. Results The drugs (propofol and MK-801) and theelectroconvulsive shock can induce the impairment of learning-memory indepressed rats, extending the evasive latency time and shorten the spaceexploration time. And both influences present subtract effect. Theelectroconvulsive shock can significantly up-regulated the content ofglutamate, which was not affected by MK-801, in the hippocampus ofdepressed rats which was reduces by the propofol. And both influencespresent subtract effects. The electroconvulsive shock and the drugs do notaffect the total protein Tau in the hippocampus of rats. Theelectroconvulsive shock can up-regulated the hyperphosphorylation ofprotein Tau in the hippocampus of depressed rats which is can be reducedby propofol and MK-801. And the influences between theelectroconvulsive shock and the drugs present subtract effects. Our resultsindicate that the electroconvulsive shock up-regulated the content ofglutamate in the hippocampus of depressed rats, which up-regulated thehyperphosphorylation of protein Tau which can induce the impairment oflearning-memory in depressed rats; and propofol protects against the impairment of learning-memory and reduce the hyperphosphorylation ofprotein Tau induced by electroconvulsive shock in depressed rats. GSK-3βis the key protein in this signaling pathway. Conclusions Our resultsindicate that the electroconvulsive shock reduce the impairment oflearning-memory the hyperphosphorylation of protein Tau in depressed ratsthough up-regulated the content of glutamate.
PART Ⅴ
Comparison of the neuropsychology mechanisms of propofol,ginsenoside Rg-1and lithium protects against the impairment oflearning-memory induced by electroconvulsive shock in depressed rats
Objective This study explore the reversion of propofol, ginsenosideRg-1, lithium against the impairment of learning-memory and thehyperphosphorylation of protein Tau induced by electroconvulsive shockand the concentration of glutamic acid in the hippocampus in depressed rats.Methods As the analysis of variance of factorial design set up twointervention factors which are the electroconvulsive shock groups (twolevels: no disposition; A course of electroconvulsive shock) and the drugintervention groups (four levels: Microinjection of propofol, ginsenosideRg-1and lithium,20μg1μl-1). Sixty-four adult depression model rats whoseolfactory bulbs were removed were randomly divided into eightexperimental groups (n=8, in each group). The Morris water maze teststarted within1day after the course of electroconvulsive shock finished inorder to evaluate learning-memory. Detect of the content of glutamate inthe hippocampus of rats by High Performance Liquid Chromatography.Detect of the content of protein Tau which includes Tau-5and p-AT8Ser202in the hippocampus of rats with the methods of Western blotting test.Results Propofol and the electroconvulsive shock can induce theimpairment of learning-memory in depressed rats. Ginsenoside Rg-1and lithium can protects against the impairment of learning-memory induced byelectroconvulsive shock in depressed rats. The electroconvulsive shock cansignificantly up-regulated the content of glutamate, which was reduces bypropofol. The electroconvulsive shock can up-regulated thehyperphosphorylation of protein Tau in the hippocampus of depressed ratswhich is can be reduced by these three medicines. Conclusions Our resultsindicate that propofol, ginsenoside Rg-1and lithium protects against theimpairment of learning-memory induced by electroconvulsive shock indepressed rats though reducing the hyperphosphorylation of protein Tau.The first two is not content with the glutamate in the hippocampus, withwhich lithium is not content.
CONCLUSIONS OF THE TATOL PAPER
Our results indicate that the electroconvulsive shock up-regulated thecontent of glutamate in the hippocampus of depressed rats, whichup-regulated the hyperphosphorylation of protein Tau throughup-regulating the expression of GSK-3β1H8, which can induce theimpairment of learning-memory in depressed rats. Propofol protects againstthe impairment of learning-memory and reduce the hyperphosphorylationof protein Tau induced by electroconvulsive shock in depressed ratsthrough reducing the expression of GSK-3β1H8and the content of glutamatein the hippocampus. GluR antagonists, ginsenoside Rg-1and lithiumprotects against the impairment of learning-memory induced byelectroconvulsive shock in depressed rats though reducing thehyperphosphorylation of protein Tau, too.
引文
[1] Michael H, Ebert current diagnosis and treatment psychiatry[M].2th ed. NewYork: Mc Graw-Hill Press,2008,306-307
[2] Conrad MS, Richard A. The handbook for electroconvulsive therapy[M].California: Eagle Race Medical Technologies Company Press,1999,13-15
[3] Luo J, Min S, Wei K, et al. Propofol protects against impairment oflearning-memory and imbalance of hippocampal Glu/GABA induced byelectroconvulsive shock in depressed rats[J]. J Anesth,2011,25(5):657-665
[4] Andrade C, Singh NM, Thyagarajan S, et al. Possible glutamatergic and lipidsignalling mechanisms in ECT-induced retrograde amnesia: experimentalevidence for involvement of COX-2, and review of literature[J]. J Psychiatr Res,2008,42(10):837-850
[5] Dong J, Min S, Wei K, Li P, Cao J, Li Y.Effects of electroconvulsive therapy andpropofol on spatial memory and glutamatergic system in hippocampus ofdepressed rats[J]. J ECT,2010,26(2):126-130
[6] Kartalci S, Karabulut AB, Ozcan AC, et al. Acute and chronic effects ofelectroconvulsive treatment on oxidative parameters in schizophrenia patients[J].Prog Neuropsychopharmacol Biol Psychiatry,2011,35(7):1689-1694
[7] Kato N. Neurophysiological mechanisms of electroconvulsive therapy fordepression[J]. Neurosci Res,2009,64(1):3-11
[8] Cudalbu C, Lanz B, Duarte JM, Morgenthaler FD, Pilloud Y, Mlynárik V,Gruetter R. Cerebral glutamine metabolism under hyperammonemia determinedin vivo by localized (1)H and (15)NNMR spectroscopy[J]. J Cereb Blood FlowMetab,2011, DOI:10.1038/jcbfm.2011.173
[9] Kloda A, Martinac B, Adams DJ. Polymodal regulation of NMDA receptorchannels[J]. Channels (Austin),2007,1(5):334-343
[10] Allyson J, Dontigny E, Auberson Y, et a1. Blockade of NR2A-containingNMDA receptors induces Tau phosphorylation in rat hippocampal slices[J].Neural Plast,2010, DOI:10.1155/2010/340168
[11] Bardo S, Cavazzini MG, Emptage N. The role of the endoplasmic reticulum Ca2+store in the plasticity of central neurons[J]. Trends Pharmacol Sci,2006,27(2):78–84
[12]李玺，刘颖，张欣，等.人参皂苷Rg1对大鼠脑片AD模型磷酸化Tau蛋白及NMDA受体亚单位NR1，NR2B表达的影响[J].中国中药杂志，2010，35(24)：3339-3343
[13] MaláH, Chen Y, Worm VH. Cognitive enhancing effects of an AMPA receptorpositive modulator on place learning in mice[J]. Behav Brain Res,2012,226(1):18–25
[14] Dennis SH, Jaafari N, Cimarosti H, et al. Oxygen/glucose deprivation induces areduction in synaptic NMDA receptors on hippocampal CA3neurons mediatedby mGluR1and adenosine A3receptors[J]. J Neurosci,2011,31(33):11941-11952
[15] Vieira M, Fernandes J, Burgeiro, et al. Excitotoxicity through Ca2+-permeableNMDA receptors requires Ca2+-dependent JNK activation[J]. Neurobiol Dis,2010,40(3):645-655
[16] Nakamoto M, Nalavadi V, Epstein MP, et al. Fragile X mental retardation proteindeficiency leads to excessive mGluR5-dependent internalization of NMDAreceptors[J]. Proc Natl Acad Sci USA,2007,104(39):15537-15542
[17] Bliss RM, Finckbone VL, Trice J, et al. Tumor necrosis factor-α (TNF-α)augments NMDA-induced purkinje neuron toxicity[J]. Brain Res,2011,1836(1):1-14
[18] Shutter L, Tong KA, Holshouser BA. Proton MRS in acute traumatic brain injury:role for glutamate/glutamine and choline for outcome prediction[J]. JNeurotrauma,2004,21(12):1693-1705
[19] Liu Z, Li H, Zhang W, et al. Neuregulin-1β prevents Ca2+overloading andapoptosis through PI3K/Akt activation in cultured dorsal root ganglion neuronswith excitotoxicity induced by glutamate[J]. Cell Mol Neurobiol,2011,31(8):1195-1201
[20] Lehtihet M, Honkanen RE, Sj holm A. Glutamate inhibits protein phosphatasesand promotes insulin exocytosis in pancreatic beta-cells[J]. Biochem BiophysRes Commun,2005,328(2):601-607
[21] Bibow S, Ozenne V, Biernat J, et al. Structural impact of proline-directedpseudophosphorylation at AT8, AT100, and PHF1epitopes on441-residueTau[J]. J Am Chem Soc,2011,133(40):15842-15845
[22]李洁颖，晏勇，蔡志友，等.胰岛素信号通路磷脂酰肌醇-3激酶/丝氨酸苏氨酸蛋白激酶对海马神经元β-淀粉样前体蛋白裂解酶1表达的影响[J].中华神经科杂志，2009，42(11)：737-741
[23] Chin PC, Majdzadeh N, D'Mello SR. Inhibition of GSK3beta is a common eventin neuroprotection by different survival factors[J]. Brain Res Mol Brain Res,2005,137(1-2):193-201
[24] Wu FY, Feng Q, Cheng M, et al. The activation of excitatory amino acidreceptors is involved in tau phosphorylation induced by cold water stress[J].Prog Biochem Biophys,2010,37(5):510-516
[25] Petroni D, Tsai J, Mondal D, et al. Attenuation of low dose methylmercury andglutamate induced-cytotoxicity and tau phosphorylation by anN-methyl-D-aspartate antagonist in human neuroblastoma (SHSY5Y) cells[J].Environ Toxicol,2011, DOI:10.1002/tox.20765
[26] Vossel KA, Zhang K, Brodbeck J, et al. Tau reduction prevents abeta-induceddefects in axonal transport[J]. Science,2010,333(6001):198
[27] Sato S, Xu J, Okuyama S, et al. Spatial learning impairment, enhancedCDK5/p35activity, and downregulation of NMDA receptor expression intransgenic mice expressing tau-tubulin kinase1[J]. J Neurosci,2008,28(53):14511-14521
[28] Weingarten MD, Lockwood AH, Hwo SY, et al. A protein factor essential formicrotubule assembly[J]. Proc Natl Acad Sci USA,1975,72(5):1858-1862
[29] Cleveland DW, Hwo SY, Kirschner MW. Purification of Tau, amicrotubule-associated protein that induces assembly of microtubules frompurified tubulin[J]. J Mol Biol,1977,116(2):207-225
[30] Binder LI, Frankfurter A，Rebhun LI. The distribution of tau in the mammaliancentral nervous system[J]. J Cell Biol,1985,101(4):1371-1378
[31] Panda D, Goode BL, Feinstein SC, et al. Kinetic stabilization of microtubuledynamics at steady state by tau and microtubule-binding domains of tau[J].Bioehemistry,1995,34(35):11117-11127
[32] Osiecka KM, Nieznanska H, Skowronek KJ, et al. Tau inhibits tubulinoligomerization induced by prion protein[J]. Biochim Biophys Acta,2010,1813(10):1845-1853
[33] De Calignon A, Fox LM, Pitstick R, et al. Caspase activation precedes and leadsto tangles[J]. Nature2010,464(16):1201-1204
[34]王建枝，龚成新，I Grundke-Iqbal，等.阿尔茨海默病tau蛋白异常修饰与其功能的关系[J].生物化学与生物物理进展，1999，26(2)：154-157
[35] Naqvi SH，王维山，苗君叶，等.甲醛诱导Tau蛋白形成“孔道样”聚集结构[J].生物化学与生物物理进展，2010，37(11)：1195-1203
[36] Combs B, Voss K, Gamblin TC, et al. Pseudohyperphosphorylation hasdifferential effects on polymerization and function of tau isoforms[J].Biochemistry,2011,50(44):9446-9456
[37]李芳序，卢静，许亚杰，等.老年性痴呆发病过程中内源性甲醛慢性损伤机制[J].生物化学与生物物理进展，2008，35(4)：393-400
[38] Zhang B, Carroll J, Trojanowski JQ. The microtubule-stabilizing agent,epothilone d, reduces axonal dysfunction, neurotoxicity, cognitive deficits, andAlzheimer-like pathology in an interventional study with aged tau transgenicmice[J]. J Neurosci,2012,32(11):3601-3611
[39] McVicker DP, Chrin LR, Berger CL. The nucleotide-binding state ofmicrotubules modulates kinesin processivity and the ability of Tau to inhibitkinesin-mediated
[40] Giasson BI, Forman MS, Higuchi M, et al. Initiation and synergistic fibrillizationof tau and alpha-synuclein[J]. Science,2003,300(5619):636-640
[41] Onishi T, Iwashita H, Uno Y, et al. A novel glycogen synthase kinase-3inhibitor2-methyl-5-(3-{4-[(S)-methylsulfinyl]phenyl}-1-benzofuran-5-yl)-1,3,4-oxadiazole (MMBO) decreases Tau phosphorylation and amelioratescognitive deficits in a transgenic model of alzheimer's disease[J]. J Neurochem,2011,119(6):1330-1340
[42] Wang H, Zhao H, Ye Y, et al. Focal cerebral ischemia induces alzheimer'sdisease-like pathological change in rats[J]. J Huazhong Univ Sci Technolog MedSci,2010,30(1):29-36
[43] Carroll JC, Iba M, Bangasser DA, et al. Chronic stress exacerbates Tau pathology,neurodegeneration, and cognitive performance through a corticotropin-releasingfactor receptor-dependent mechanism in a transgenic mouse model oftauopathy[J]. J Neurosci,2011,31(40):14436-14449
[44] Kopeikina KJ, Carlson GA, Pitstick R, et al. Tau accumulation causesmitochondrial distribution deficits in neurons in a mouse model of tauopathy andin human Alzheimer's disease brain[J]. Am J Pathol,2011,179(4):2071-2082
[45] Liu SJ, Zhang AH, Li HL, et al. Overactivation of glycogen synthase kinase-3byinhibition of phosphoinositol-3kinase and protein kinase C leads tohyperphosphorylation of tau and impairment of spatial memory[J]. J Neurochem,2003,87(6):1333-1344
[46] Maurer K, Hoyer S. Alois Alzheimer revisited: differences in origin of thedisease carrying his name[J]. J Neural Transm2006;113(11):1645–1658
[47] Bulbarelli A, Lonati E, Cazzaniga E, et al. Pin1affects Tau phosphorylation inresponse to abeta oligomers[J]. Mol Cell Neurosci,2009,42(1):75-80
[48] Martin L, Magnaudeix A, Wilson CM, et al. The new indirubin derivativeinhibitors of glycogen synthase kinase-3,6-BIDECO and6-BIMYEO, preventtau phosphorylation and apoptosis induced by the inhibition of proteinphosphatase-2A by okadaic acid in cultured neurons[J]. J Neurosci Res,2011,89(11):1802-1811
[49] Sun Q, Gamblin TC. Pseudohyperphosphorylation causing AD-like changes intau has significant effects on its polymerization[J]. Biochemistry,2009,48(25):6002-6011
[50] Phiel CJ, Wilson CA, Lee VM, et al. GSK-3alpha regulates production ofAlzheimer's disease amyloid-beta peptides[J]. Nature,2003,423(6938):435-439
[51] Wang Q, Zhang JY, Liu SJ, et al. Overactivated mitogen-activated protein kinaseby anisomycin induces tau hyperphosphorylation[J]. Acta Psiologica Sinica,2008,60(4):485-491
[52] Fu ZQ, Yang Y, Song J, et al. LiCl attenuates thapsigargin-induced tauhyperphosphorylation by inhibiting GSK-3β in vivo and in vitro[J]. J AlzheimersDis,2010,21(4):1107-1117
[53] De Vos A, Anandhakumar J, Van den Brande J, et al. Yeast as a model system tostudy tau biology[J]. Int J Alzheimers Dis,2011, DOI:10.4061/2011/428970
[54] Kawakami F, Suzuki M, Shimada N, et al. Stimulatory effect of α-synuclein onthe tau-phosphorylation by GSK-3β[J]. FEBS J,2011,278(24):4895-4904
[55] Giese KP. GSK-3: a key player in neurodegeneration and memory[J]. IUBMBLife,2009,61(5):516-521
[56] Blazquez-Llorca L, Garcia-Marin V, Merino-Serrais P, et al. Abnormal Tauphosphorylation in the thorny excrescences of CA3hippocampal neurons inpatients with alzheimer's disease[J]. J Alzheimers Dis,2011,26(4):683-698
[57] Popkie AP, Zeidner LC, Albrecht AM, et al. Phosphatidylinositol3-kinase (PI3K)signaling via glycogen synthase kinase-3(Gsk-3) regulates DNA methylation ofimprinted loci[J]. J Biol Chem,2010,285(53):41337-41347
[58]郭建荣，岳云，崔健君，等.异丙酚对缺血再灌注损伤大鼠海马氨基酸递质水平变化及神经元凋亡的影响[J].病理生理学杂志，2007，23(8)：1547-1550
[59]曾育琦,陈晓春,黄春,等.人参皂苷Rgl通过调节GSK-13/PP2A活性减轻皮层神经元Tau蛋白过度磷酸化[J].解剖学报,2000，38(6)：665-670
[60] Liang Z, Liu F, Iqbal K, et al. Decrease of protein phosphatase2A and itsassociation with accumulation and hyperphosphorylation of tau in Downsyndrome[J]. J Alzheimers Dis,2008,13(3):295-320
[61] Zhang Y, Liang J, Sun L, et al. Inhibition of PP-2A and the consequent activationof JNK/c-Jun are involved in tributyltin-induced apoptosis in human amnioniccells[J]. Environ Toxicol,2011, doi:10.1002/tox.20730
[62]薛海波.阿尔茨海默病的神经心理学和神经化学诊断研究[Ｄ].上海交通大学，2006
[63]中华医学会神经病学分会痴呆与认知障碍学组写作组.血管性认知障碍诊治指南，中华神经科杂志，2011，44(2)：142-147
[64] Jia JP, Meng R, Sun YX, et al. Cerebrospinal fluid tau, Abetal-42andinflammatory cytokines in patients with Alzheimer's disease and vasculardementia[J]. Neurosci Lett,2005,383:12-16
[65] Stefani A, Bernardini S, Panella M, et al. AD with subcortical white matterlesions and vascular dementia: CSF markers for differential diagnosis[J]. JNeurol Sci,2005,237:83-88
[66] Hans P, Bonhomme V, Collette J, et al. Propofol protects cultured rathippocampal neurons against N-methyl-D-aspartate receptor-mediated glutamatetoxicity[J]. J Neurosurg Anesthesiol,1994,6(4):249-253
[67] Kingston S, Mao LM, Yang L, et al. Propofol inhibits phosphorylation ofN-methyl-D-aspartate receptor NR1subunits in neurons[J]. Anesthesiology,2006,104(4):736-739
[68] Dong J, Min S, Wei K, Li P, Cao J, Li Y.Effects of electroconvulsive therapy andpropofol on spatial memory and glutamatergic system in hippocampus ofdepressed rats[J]. J ECT,2010,26(2):126-130
[69] Yagmurdur H, Ayyildiz A, Karaguzel E, et al. Propofol reduces nitricoxide-induced apoptosis in testicular ischemia-reperfusion injury bydownregulating the expression of inducible nitric oxide synthase[J]. ActaAnaesthesiol Scand,2008,52(3):350-357
[70] Wang B, Shravah J, Luo H, et al. Propofol protects against hydrogenperoxide-induced injury in cardiac H9c2cells via Akt activation and Bcl-2up-regulation[J]. Biochem Biophys Res Commun,2009,389(1):105-111
[71] Xi HJ, Zhang TH, Tao T, et al. Propofol improved neurobehavioral outcome ofcerebral ischemia-reperfusion rats by regulating Bcl-2and Bax expression[J].Brain Res,2011,1410:24-32
[72] Fang F, Chen X, Huang T, et al. Multi-faced neuroprotective effects ofginsenoside Rg1in an Alzheimer mouse model[J]. Biochim Biophys Acta,2011,1822(2):286-292
[73] Jiang B, Xiong Z, Yang J, et al. Antidepressant-like effects of ginsenosideRg1produced by activation of BDNF signaling pathway and neurogenesis in thehippocampus[J]. Br J Pharmacol,2012, doi:10.1111/j.1476-5381.2012.01902.x
[74]褚燕琦，张兰，李玮，等.人参皂苷对蛋白磷酸酶抑制剂冈田酸拟阿尔采末病细胞模型的影响[J].中国药理学通报，2008，24(7)：879-884
[75] Wang YZ, Chen J, Chu SF, et al. Improvement of memory in mice and increaseof hippocampal excitability in rats by ginsenoside Rg1's metabolites ginsenosideRh1and protopanaxatriol[J]. J Pharmacol Sci,2009,109(4):504-510
[76] Zhao L, Wang F, Gui B, et al. Prophylactic lithium alleviates postoperativecognition impairment by phosphorylating hippocampal glycogen synthasekinase-3β (Ser9) in aged rats[J]. Exp Gerontol,2011,46(12):1031-1036
[77]陆文惠，屈秋民，曹红梅，等.锂对慢性铝暴露大鼠脑内CDK5和PP2A表达的影响[J].西安交通大学学报(医学版)，2010，31(4)：463-466
[78] Ponce-Lopez T, Liy-Salmeron G, Hong E, et al. Lithium, phenserine, memantineand pioglitazone reverse memory deficit and restore phospho-GSK3β decreasedin hippocampus in intracerebroventricular streptozotocin induced memorydeficitmodel[J]. Brain Res,2011,2046:73-85
[79]谭文斐，田阿勇，王俊科，等.氯化锂对脾切除大鼠海马Tau蛋白的影响[J].中国药理学通报，2010，26(11)：1526-1527
[80] Wada A, Yokoo H, Yanagita T, et al. L ithium: Potential therapeutics against acutebrain injuries and chronic neurodegenerative diseases[J]. J Pharmacol Sci,2005,99∶307-321
[81] Li X, Lu F, Tian Q, et al. Activation of glycogen synthase kinase-3inducesAlzheimer-like tau hyperphosphorylation in rat hippocampus slices in culture[J].J Neural Transm,2006,113:93-102
[82] Zhang C, Du F, Shi M, et al. Ginsenoside Rd protects neurons againstglutamate-induced excitotoxicity by inhibiting Ca(2+) influx[J]. Cell MolNeurobiol,2012,32(1):121-128
[83] Chen Z, Lu T, Yue X, et al. Neuroprotective effect of ginsenoside Rb1onglutamate-induced neurotoxicity: with emphasis on autophagy[J]. Neurosci Lett,2010,482(3):264-268
[84] Li XY, Liang J, Tang YB, et al. Ginsenoside Rd prevents glutamate-inducedapoptosis in rat cortical neurons[J]. Clin Exp Pharmacol Physiol,2010,37(2):199-204
[85] Kandel ER.The moleeular biology of memory storage: a dialogue between genesand synapses[J]. Sience,2001,294(5544):1030-1038
[86]于萍，袁水霞，李霞，等.记忆过程中海马CA1区神经元的集群放电特征[J].心理学报，2011，43(8)：917-928
[87]倪兵，钱晨灿，吴睿洁，等.海马参与工作记忆目标匹配增强及其时间过程—基于颅内脑电的研究[J].生物化学与生物物理进展，2011，38(11)：1027-1035
[88] Choi BR, Kwon KJ, Park SH, et al. Alternations of septal-hippocampal system inthe adult wistar rat with spatial memory impairments induced by chroniccerebral hypoperfusion[J]. Exp Neurobiol,2011,20(2):92-99
[89] Preissmann D, Bertholet L, Sierro G, et al. Accurate performance of a rat modelof schizophrenia in the water maze depends on visual cue availability andstability: a distortion in cognitive mapping abilities?[J]. Behav Brain Res,2011,223(1):145-153
[90] Nishida Y, Yokotat, Takaijashit, etal. Deletion of vitamin E enhanees phenotypeof Alzheimer disease model mouse[J]. Bioehem Biophys Res Commun,2006,350(3):530-536
[91] Wu QY, Li J, Feng ZT, et al. Bone marrow stromal cells of transgenic mice canimprove the cognitive ability of an AIZheimer,s disease rat model[J]. NeurosciLett,2007,417(3):281-285
[92] Harvey BH, Naciti C, Brand L, et al. Endocrine, eognitiveand hippocampal/cortical5HT1A/2A receptor changes evoked by a time-dependent sensitization(TDS) stress model in rats[J]. BrainRes,2003,983(l-2):97-107
[93] Nicholasa, Mijnhozcd, Fergusond E，et al. Enhancing cognition after stress withgene therapy[J]. J Neurosci,2006,26(45):11637-11643
[1] Michael H, Ebert. Current diagnosis and treatment psychiatry[M].2th ed. NewYork: Mc Graw-Hill Press,2008,306-307
[2] Conrad MS, Richard A. The handbook for electroconvulsive therapy[M].California: Eagle Race Medical Technologies Company Press,1999,13-15
[3] Luo J, Min S, Wei K, et al. Propofol protects against impairment oflearning-memory and imbalance of hippocampal Glu/GABA induced byelectroconvulsive shock in depressed rats[J]. J Anesth,2011,25(5):657-665
[4] Andrade C, Singh NM, Thyagarajan S, et al. Possible glutamatergic and lipidsignalling mechanisms in ECT-induced retrograde amnesia: experimental evidencefor involvement of COX-2, and review of literature[J]. J Psychiatr Res,2008,42(10):837-850
[5] Dong J, Min S, Wei K, et al. Effects of electroconvulsive therapy and propofol onspatial memory and glutamatergic system in hippocampus of depressed rats[J]. JECT,2010,26(2):126-130
[6] Kartalci S, Karabulut AB, Ozcan AC, et al. Acute and chronic effects ofelectroconvulsive treatment on oxidative parameters in schizophrenia patients[J].Prog Neuropsychopharmacol Biol Psychiatry,2011,35(7):1689-1694
[7] Kato N. Neurophysiological mechanisms of electroconvulsive therapy fordepression[J]. Neurosci Res,2009,64(1):3-11
[8] Kloda A, Martinac B, Adams DJ. Polymodal regulation of NMDA receptorchannels[J]. Channels (Austin),2007,1(5):334-343
[9] Dennis SH, Jaafari N, Cimarosti H, et al. Oxygen/glucose deprivation induces areduction in synaptic NMDA receptors on hippocampal CA3neurons mediated bymGluR1and adenosine A3receptors[J]. J Neurosci,2011,31(33):11941-11952
[10] Vieira M, Fernandes J, Burgeiro, et al. Excitotoxicity through Ca2+-permeableNMDA receptors requires Ca2+-dependent JNK activation[J]. Neurobiol Dis,2010,40(3):645-655
[11] Bliss RM, Finckbone VL, Trice J, et al. Tumor necrosis factor-α (TNF-α)augments NMDA-induced Purkinje neuron toxicity[J]. Brain Res,2011,1836(1):1-14
[12] Shutter L, Tong KA, Holshouser BA. Proton MRS in acute traumatic brain injury:role for glutamate/glutamine and choline for outcome prediction[J]. JNeurotrauma,2004,21(12):1693-1705
[13] Wu FY, Feng Q, Cheng M, et al. The activation of excitatory amino acidreceptors is involved in tau phosphorylation induced by cold water stress[J]. ProgBiochem Biophys,2010,37(5):510-516
[14] Petroni D, Tsai J, Mondal D, et al. Attenuation of low dose methylmercury andglutamate induced-cytotoxicity and tau phosphorylation by anN-methyl-D-aspartate antagonist in human neuroblastoma (SHSY5Y) cells[J].Environ Toxicol,2011, DOI:10.1002/tox.20765
[15] Weingarten MD, Lockwood AH, Hwo SY, et al. A protein factor essential formicrotubule assembly[J]. Proc Natl Acad Sci USA,1975,72(5):1858-1862
[16] Osiecka KM, Nieznanska H, Skowronek KJ, et al. Tau inhibits tubulinoligomerization induced by prion protein[J]. Biochim Biophys Acta,2010,1813(10):1845-1853
[17] Cleveland DW, Hwo SY, Kirschner MW. Purification of Tau, a microtubule-associated protein that induces assembly of microtubules from purified tubulin[J].J Mol Biol,1977,116(2):207-225
[18] De Calignon A, Fox LM, Pitstick R, et al. Caspase activation precedes and leadsto tangles[J]. Nature2010,464(16):1201-1204
[19] Combs B, Voss K, Gamblin TC, et al. Pseudohyperphosphorylation hasdifferential effects on polymerization and function of tau isoforms[J].Biochemistry,2011,50(44):9446-9456
[20] Canu N, Filesi I, PristeràA, et al. Altered intracellular distribution of PrPC andimpairment of proteasome activity in Tau overexpressing cortical neurons[J]. JAlzheimers Dis,2011,27(3):603-613
[21] Onishi T, Iwashita H, Uno Y, et al. A novel glycogen synthase kinase-3inhibitor2-methyl-5-(3-{4-[(S)-methylsulfinyl]phenyl}-1-benzofuran-5-yl)-1,3,4-oxadiazole (MMBO) decreases Tau phosphorylation and ameliorates cognitivedeficits in a transgenic model of alzheimer's disease[J]. J Neurochem,2011, DOI:10.1111/j.1471-4159.2011.07532.x
[22] Kopeikina KJ, Carlson GA, Pitstick R, et al. Tau accumulation causesmitochondrial distribution deficits in neurons in a mouse model of tauopathy andin human Alzheimer's disease brain[J]. Am J Pathol,2011,179(4):2071-2082
[23] Wang Q, Zhang JY, Liu SJ, et al. Overactivated mitogen-activated protein kinaseby anisomycin induces tau hyperphosphorylation[J]. Acta Psiologica Sinica,2008,60(4):485-491
[24] Fu ZQ, Yang Y, Song J, et al. LiCl attenuates thapsigargin-induced tauhyperphosphorylation by inhibiting GSK-3β in vivo and in vitro[J]. J AlzheimersDis,2010,21(4):1107-1117
[25] De Vos A, Anandhakumar J, Van den Brande J, et al. Yeast as a model system tostudy tau biology[J]. Int J Alzheimers Dis,2011, DOI:10.4061/2011/428970
[26] Blazquez-Llorca L, Garcia-Marin V, Merino-Serrais P, et al. Abnormal Tauphosphorylation in the thorny excrescences of CA3hippocampal neurons inpatients with alzheimer's disease[J]. J Alzheimers Dis,2011,26(4):683-698
[27] Bibow S, Ozenne V, Biernat J, et al. Structural impact of proline-directedpseudophosphorylation at AT8, AT100, and PHF1epitopes on441-residue Tau[J].J Am Chem Soc,2011,133(40):15842-15845
[28] Ray P, Kar A, Fushimi K, et al. PSF suppresses Tau exon10inclusion byinteracting with a stem-loop structure downstream of exon10[J]. J Mol Neurosci,2008,45(3):453-466
[29] Bibow S, Mukrasch MD, Chinnathambi S, et al. The dynamic structure offilamentous Tau[J]. Angew Chem Int Ed Engl,2011, DOI:10.1002/anie.201105493
[30] Chin PC, Majdzadeh N, D'Mello SR. Inhibition of GSK3beta is a common eventin neuroprotection by different survival factors[J]. Brain Res Mol Brain Res,2005,137(1-2):193-201
[31] Lehtihet M, Honkanen RE, Sj holm A. Glutamate inhibits protein phosphatasesand promotes insulin exocytosis in pancreatic beta-cells[J]. Biochem Biophys ResCommun,2005,328(2):601-607
[32] Kingston S, Mao LM, Yang L, et al. Propofol inhibits phosphorylation ofN-methyl-D-aspartate receptor NR1subunits in neurons[J]. Anesthesiology,2006,104(4):736-739
[33] Hans P, Bonhomme V, Collette J, et al. Propofol protects cultured rathippocampal neurons against N-methyl-D-aspartate receptor-mediated glutamatetoxicity[J]. J Neurosurg Anesthesiol,1994,6(4):249-253
[34] Fang F, Chen X, Huang T, et al. Multi-faced neuroprotective effects ofginsenoside Rg1in an Alzheimer mouse model[J]. Biochim Biophys Acta,2011,1822(2):286-292
[35] Zhao L, Wang F, Gui B, et al. Prophylactic lithium alleviates postoperativecognition impairment by phosphorylating hippocampal glycogen synthasekinase-3β (Ser9) in aged rats[J]. Exp Gerontol,2011,46(12):1031-1036
[36] Tasset I, Medina FJ, Pena J, et al. Olfactory bulberctomy induced oxidative andcell damage in rat: protective effect of melatoni[J]. Physiol Res,2010,59(2):105-112
[37] Will CC, Aird F, Redei EE. Selectively bred Wistar-Kyoto rats: an animal modelof depression and hyper-responsiveness toantidepressants[J]. Mol Psychiatry,2003,8(11):925-932
[38] Tejani-Butt S, Kluczynski J, ParéWP. Strain-dependent modification of behaviorfollowing antidepressant treatment[J]. Prog Neuropsychopharmacol BiolPsychiatry,2003,27(1):7-14
[39] Mutlu O, Ulak G, Celikyurt IK, et al. Effects of olanzapine, sertindole andclozapine on learning and memory in the Morris water maze test in naive andMK-801-treated mice[J]. Pharmacol Biochem Behav,2011,98(3):398-404
[40] Barat SA, Abdel-Rahman MS. Decreased cocaine and lidocaine-induced seizureresponse by dextromethorphan and DNQX in rat[J]. Brain Res,2011,756(1-2):179-183
[41] Altar CA, Laeng P, Jurata LW, et al. Electroconvulsive seizures regulate geneexpression of distinct neurotrophic signaling pathways[J]. J Neuresci,2004,24(11):2667-2677
[42] Wang D, Noda Y, Tsunekawa H, et al. Bshavioural and neurochemical feaures ofolfactory bulbertomized rats resembling depression with co-morbid anixiety[J].Behav Brain Res,2007,178(2):262-273
[43] Kato S, Kito Y, Hemmi H, et al. Simultaneous determination of D-amino acidsby the coupling method of D-amino acid oxidase with high-performance liquidchromatography[J]. J Chromatogr B Analyt Technol Biomed Life Sci,2011,879(29):3190-3195
[44] Choi BR, Kwon KJ, Park SH, et al. Alternations of septal-hippocampal system inthe adult Wistar rat with spatial Memory impairments induced by chronic cerebralhypoperfusion[J]. Exp Neurobiol,2011,20(2):92-99
[45] Preissmann D, Bertholet L, Sierro G, et al. Accurate performance of a rat modelof schizophrenia in the water maze depends on visual cue availability andstability: a distortion in cognitive mapping abilities?[J]. Behav Brain Res,2011,223(1):145-153
[46] Carroll JC, Iba M, Bangasser DA, et al. Chronic stress exacerbates Tau pathology,neurodegeneration, and cognitive performance through a corticotropin-releasingfactor receptor-dependent mechanism in a transgenic mouse model ofTauopathy[J]. J Neurosci,2011,31(40):14436-14449
[47] Palmio J, Huuhka M, Laine S, et al. Electroconvulsive therapy and biomarkers ofneuronal injury and plasticity: serum levels of neuron-specific enolase andS-100b protein[J]. Psychiatry Res,2010,177(1-2):97-100
[48] Stover JF, Kempski OS. Anesthesia increases circulating glutamate inneurosurgical patients[J]. Acta Neurochir (Wien),2005,147(8):847-853
[49] Feiner JR, Bickler PE, Estrada S, et al. Mild hypothermia, but not propofol, isneuroprotective in organotypic hippocampal cultures[J]. Anesth Analg,2005,100(1):215-225
[50] Li KY, Guan YZ, Krnjevi K, et al. Propofol facilitates glutamatergictransmission to neurons of the ventrolateral preoptic nucleus[J]. Anesthesiology,2009,111(6):1271-1278
[51] Pesi V, Milanovi D, Tani N, et al. Potential mechanism of cell death in thedeveloping rat brain induced by propofol anesthesia[J]. Int J Dev Neurosci,2009,27(3):279-287
[52] Nie CL, Wang XS, Liu Y, et al. Amyloid-like aggregates of neuronal tau inducedby formaldehyde promote apoptosis of neuronal cells[J]. BMC Neuroscience,2007,23(8):9
[53] Yao Z, Guo Z, Yang C, et al. Phenylbutyric acid prevents rats fromelectroconvulsion-induced memory deficit with alterations of memory-relatedproteins and tau hyperphosphorylation[J]. Neuroscience,2010,168(2):405-415
[54] Bulbarelli A, Lonati E, Cazzaniga E, et al. Pin1affects Tau phosphorylation inresponse to Abeta oligomers[J]. Mol Cell Neurosci,2009,42(1):75-80
[55] Tan W, Cao X, Wang J, et a1. Tau hyperphosphorylation is associated withmemory impairment after exposure to1.5%isoflurane without temperaturemaintenance in rats[J]. Eur J Anaesthesiol,2010,27(9):835-841
[56] Vossel KA, Zhang K, Brodbeck J, et al. Tau reduction prevents Abeta-induceddefects in axonal transport[J]. Science,2010,333(6001):198
[57] Allyson J, Dontigny E, Auberson Y, et a1. Blockade of NR2A-containingNMDA receptors induces Tau phosphorylation in rat hippocampal slices[J].Neural Plast,2010, DOI:10.1155/2010/340168
[58] Sato S, Xu J, Okuyama S, et a1. Spatial learning impairment, enhancedCDK5/p35activity, and downregulation of NMDA receptor expression intransgenic mice expressing tau-tubulin kinase1[J]. J Neurosci,2008,28(53):14511-14521
[59] Muyllaert D, Kremer A, Jaworski T, et a1. Glycogen synthase kinase-3beta, or alink between amyloid and tan pathology[J]. Genes Brain Behav,2008,7(Suppl1):57-66
[60] Xu JJ, Wang YL. Propofol attenuation of hydrogen peroxide-mediated oxidativestress and apoptosis in cultured cardiomyocytes involves haeme oxygenase-1[J].Eur J Anaesthesiol,2008,25(5):395-402
[61] Straiko MM, Young C, Cattano D, et a1. Lithium protects againstanesthesia-induced developmental neuroapoptosis[J]. Anesthesiology,2009,110(4):862-868
[62] Klein RC, Warder SE, Galdzicki Z, et al. Kinetic and mechanisticcharacterization of NMDA receptor antagonism by replacement and truncationvariants of the conantokin peptides[J]. Neuropharmacology,2001,41(7):801-810
[63] Amadoro G, Ciotti MT, Costanzi M, et al. NMDA receptor mediates tau-inducedneurotoxicity by calpain and ERK/MAPK activation[J]. Proc Natl Acad Sci USA,2006,103(8):2892-2897
[64] Paterlini M, Valerio A, Baruzzi F, et a1. Opposing regulation of protein Taulevels by ionotropic and metabotropic glutamate receptors in human NT2neurons[J]. Neurosci Lett,1998,243(1-3):77-80
[65] Elyaman W, Terro F, Wong NS, et a1. In vivo activation and nucleartranslocation of phosphorylated glycogen synthase kinase-3beta in neuronalapoptosis: links to tau phosphorylation[J]. Eur J Neurosci,2002,15(4):651-660
[1] Weingarten MD, Lockwood AH, How SY, et al. A protein factor essential formicrolubule assembly[J]. Proc Nall Acard Sci USA,1975,72(5):1858-1862
[2] Cleveland DW, Hwo SY, Kirschner MW. Purification of Tau, a microtubuleassociated protein that induces assembly of microtubules from purified tubulin[J]. JMol Biol1977,116(2):207-725
[3] Hasegawa M. Biochemistry and molecular biology of Tauopathies[J].Neuropathology,2006,26(5):484-490
[4]王海均，赵洪洋，熊南翔，等.局灶性脑缺血再灌注致大鼠大脑皮质Tau蛋白异常高度磷酸化[J].华中科技大学学报(医学版)，2009，38(6)：739-743.
[5] Santacruz K, Lewis J, Spires T, et a1. Tau suppression in a neurode-generativemouse model improves memory function[J]. Science,2005,309(5733):476-481
[6]曲梅花，李辉，徐艳娟，等.人神经Tau蛋白与DNA相互作用[J].生物化学与生物物理进展，2004，31(10)：918-923
[7]盛之玲，曲梅花，何海进，等. HeLa、HEK293、SH-SY5Y细胞中的Tau蛋白[J].生物化学与生物物理进展,2008,35(12):1364-1370
[8]胡蜀红，杨雁，张建华，等.罗格列酮改善胰岛素抵抗大鼠海马Alzheimer病样Tau蛋白磷酸化水平[J].生物化学与生物物理进展，2007，34(5)：533-537
[9]苏衍萍，杜长青，王慧，等.中药髓复康对恒河猴脊髓半切后S-100、Tau蛋白表达的影响[J].解剖学杂志，2009，32(6)：778-780，784
[10] Williams DR. Tauopathies: classification and clinical update on neurodegenerativediseases associated with microtubule·associated protein Tau[J]. Intern Med J,2006,36(10):652-660
[11]张杰文，卢芬，李旭，等.叶酸和维生素B2对老年大鼠海马中Tau蛋白磷酸化的影响[J].中华神经科杂志，2007，40(1)：39-42
[12] Iqbal K, Alonso AD, Chen S, et al. Tau pathology in Alzheim erdisease and otherTauopathies[J]. Biochim Biophys Acta,2005,1739(2-3):198-210
[13]李琪，冯利杰，王海萍，等. tau蛋白的过度表达对非神经源细胞生长与分化的影响[J].中国药理学通报，2008，24(3)：365-369
[14]孙爱民，王海萍，沈玉君，等. Ser202/Thr205位点磷酸化Tau在神经元中的定位[J].中国药理学通报，2011，27(1)：41-45
[15]王鹏军，张昱，冯加纯，等. IGF-1对Aβ25-35致PC12细胞损伤的保护作用及其机制的探讨[J].中国老年学杂志，2007，27(2)：331-333
[16]张晓洁，杨雁，张木勋.1型糖尿病大鼠海马Alzheimer样磷酸酯酶2A活性降低导致Tau蛋白过度磷酸化[J].华中科技大学学报(医学版)，2009，38(1)：31-35
[17] Walton JR. An aluminum-based rat model for Alzheimer’s disease exhibitsoxidative damage inhibition of PP2A activity, hyperphosphorylated Tau andgranulovacular degeneration[J]. J Inorg Biochem,2007,101(9):1275-1284
[18]张晓洁，杨思思，张木勋，等.2型糖尿病与阿尔茨海默病互为发病风险的机制探讨[J].中国病理生理杂志，2010，26(6)：1107-1114
[19]李永坤，陈晓春，朱元贵，等.冈田酸诱导大鼠海马神经元Tau蛋白过度磷酸化[J].解剖学报，2005，36(3)：231-236
[20] Li HL, Wang SH, Lai XM, et al. Transfection with GSK-β in vivo induces Tauhyperphosphorylation at PHF-1site[J]. Chinese Journal ofPathophysiology,2006,22(3):506-510
[20]宋锦秋，陈晓春，张静，等.凝聚态Aβ25-35可通过JNK/p38MAPK途径诱导胎鼠皮层神经元Tau蛋白过度磷酸化[J].解剖学报，2007，38(5)：533-536
[21] Wang Q, Zhang JY, Liu SJ, et al. Overactivated mitogen-activated protein kinaseby anisomycin induces Tau hyperphosphorylation[J]. Acta Psiologica Sinica,2008,60(4):485-491
[22] Beurei E, Blivet-Van EM, Kornprobst M, et a1. Glycogen synthasc kinase-3inhibitors augment TRAIL induced apoptotic death in human hepatoma ce1ls[J].Biochemical Pharmacology,2009,77:54-65
[23] Sehafer BA, Bertram L, Miller BL, et a1. Association of GSK3B with Alzheimerdisease and frontotemporal dementia[J]. Arch Neurol,2008,65(10):1368-1374
[24]王海均，赵洪洋，熊南翔，等.局灶性脑缺血再灌注致大鼠大脑皮质Tau蛋白异常高度磷酸化[J].华中科技大学学报(医学版)，2009，38(6)：739-743
[25] Giese KP. GSK-3: a key player in neu rodegeneration and m emory[J]. IUBMBLife,2009,61(5):516-521
[26] Sun Q, Gamb lin TC. Pseudohyperphosphory lat ion caus ing AD-like changes inTau has sign if icant effects on its polym erizat ion[J]. Biochemistry,2009,48(25):6002-6011
[27] Qian W, Shi J, Liu F, et a1. PP2A regulates tan phosphorylation directly and alsoindirectly via activating GSK-3beta[J]. J Ahheimers DIS,2009,19(4):1221-1229
[28]刘飞，施建华，丁绍红，等.糖元合成酶激酶3β对微管相关蛋白Tau的磷酸化作用[J].生物化学与生物物理进展，2007，34(9)：945-951
[29] Muyllaert D, Kremer A, Jaworski T, et a1. Glycogen synthase kinase-3beta, or alink between amyloid and tan pathology[J]. Genes Brain Behav,2008,7(Suppl1):57-66
[30] Park YJ, Jang YM, Kwon YH. Isoflavones prevent endoplasmic reticulumstress-mediated neuronal degeneration by inhibiting Tau hyperphosphorylation inSH2SY5Y cells[J]. J Med Food,2009,12(3):528-535
[31]王鹏军，尚宏，宋荣蓉，等. MCI-186减轻Aβ1-40诱导PC12细胞Tau蛋白磷酸化的研究[J].中国老年学杂志，2009，29(20)：2624-2627
[32] Utreras E, Maccioni R, Gonza lez-Billault C. Cycl in-dependent kinase5activator p35over expression and amy loid beta synergism in crease apoptos is incu ltured neuronal cells[J]. Neuroscience,2009,161(4):978-987
[33] Deters N, Ittner LM, G tz J. Substrate specific reduction of PP2A activityexaggerates Tau pathology[J]. Biochem Biophys Res Commun,2009,379(2):400-405
[33] Bulbarlli A, Lonti E, Cazzaniga E, et al. Pin1affects Tau phosphorylation inresponse to Abeta oligomers[J]. Mol Cell Neurosci,2009,4(1):75-80
[34] Lim J, BalastikM, Lee TH, et al. Pin1has opposite effects on wild type andP301L Tau stab ility and Tauopathy[J]. J C lin Invest,2008,118(5):1877-1889
[35] Tortosa E, Santa-Maria I, Moreno F, et al. Binding of Hsp90to Tau promotes aconform ational change and aggregat ion of protein Tau[J]. J Alzheimers Dis,2009,17(2):319-325
[36] Wang JZ, Lira F. Miemtubule-associated protein Tau in development,degeneration and protection of neurons[J]. Progress in NeurobiologY,2008,85(2):148-175
[37]褚燕琦，张兰，李玮，等.人参皂苷对蛋白磷酸酶抑制剂冈田酸拟阿尔采末病细胞模型的影响[J].中国药理学通报，2008，24(7)：879-884
[38]王群，胡志红，王建枝，等.反复饥饿对大鼠空间学习及海马神经元骨架蛋白磷酸化的影响[J].中国生物化学与分子生物学报，2010，26(11)：1023-1027
[40] Reynolds CH, Garwood CJ, Wray S, et al. Phosphoryla ion regulates Tau interactions with Src homology3domains of phosphatidy linositol3-kinase,phospholipase Cgamma1, Grb2, and Src family kinase[J]. J Biol Chem,2008,283(26):18177-18186
[41] Sergeant N, Bretteville A, Hamdane M, et a1. Biochemistry of tall in Alzheimer,sdisease and related neurologieal disorders[J]. Expert Rev Proteomies,2008,5(2):207-241
[42]邓娟，周华东，李敬诚，等.吸烟对AD大鼠认知功能和Tau蛋白异常磷酸化的影响[J].中国行为医学科学，2007，16(7)：591-593
[43]杨江勇，顾建兰，施建华，等. O-GlcNAc糖基转移酶(OGT)基因表达的抑制对Tau蛋白磷酸化作用的影响[J].生物化学与生物物理进展，2009，6(3)：346-352
[44]汪建华，王学峰，龚云，等.耐药性癫痫患者术后脑组织中Tau蛋白的表达[J].中华神经科杂志，2005，38(9)：665-670
[45]段萍，李夏春，邓艳秋，等. Caspase-3对磷酸化Tau蛋白截断作用的研究[J].生物化学与生物物理进展，2010，32(1)：81-85
[50] Alix de C, Leora MF, Rose P, et a1. Caspase activation precedes and leads totangles[J]. Nature,2010,464(16):1201-1204
[51]盛之玲，刘延英，陈岚，等.非酶糖基化对α-synuclein分子构象的影响[J].生物化学与生物物理进展，2008，35(10)：1202-1208
[52]李芳序，卢静，许亚杰，等.老年性痴呆发病过程中内源性甲醛慢性损伤机制[J].生物化学与生物物理进展，2008，35(4)：393-400
[1] Andrade C, Singh NM, Thyagarajan S, et a1. Possible glutamatergic and lipidsignalling mechanisms in ECT-induced retrograde amnesia: experimental evidencefor involvement of COX-2, and review ofliterature[J]. J Psychiatr Res,2008,42(10):837-850
[2]何永光，王祖承，王飙，等.无抽搐电休克治疗抑郁症患者前后的听觉P300对照研究[J].上海精神医学，2008，20(1)：36-37,64
[3]何开华，闵苏.异丙酚在无抽搐电休克治疗中镇静的效果评价[J].重庆医科大学学报，2007，32(1)：65-66,85
[4] Butterfield NN, Graf P, Macleod BA, et al. Propofol reduces cognitive impairmentafter electroconvulsive therapy[J]. J ECT,2004,20(1):3-9
[5]黎平，闵苏，魏珂，等.异丙酚联合电休克治疗对抑郁大鼠行为学和学习记忆功能的影响[J].中华麻醉学杂志，2007，27(10)：940-943
[6] Dennis SH, Jaafari N, Cimarosti H, et al. Oxygen/glucose deprivation induces areduction in synaptic AMPA receptors on hippocampal CA3neurons mediated bymGluR1and adenosine A3receptors[J]. J Neurosci,2011,31(33):11941-11952
[7] Vieira M, Fernandes J, Burgeiro, et al. Excitotoxicity through Ca2+-permeableNMDA receptors requires Ca2+-dependent JNK activation[J]. Neurobiol Dis,2010,40(3):645-655
[8] Bliss RM, Finckbone VL, Trice J, et al. Tumor necrosis factor-α (TNF-α)augments NMDA-induced Purkinje neuron toxicity[J]. Brain Res,2011,1836(1):1-14
[9] Luo J, Min S, Wei K, et al. Propofol protects against impairment oflearning-memory and imbalance of hippocampal Glu/GABA induced byelectroconvulsive shock in depressed rats[J]. J Anesth,2011,25(5):657-665
[10] Kartalci S, Karabulut AB, Ozcan AC, et al. Acute and chronic effects ofelectroconvulsive treatment on oxidative parameters in schizophrenia patients[J].Prog Neuropsychopharmacol Biol Psychiatry,2011,35(7):1689-1694
[11] Kato N. Neurophysiological mechanisms of electroconvulsive therapy fordepression[J]. Neurosci Res,2009,64(1):3-11
[12] Matsuyama, S; Taniguchi, T; Kadoyama, K. et al. Long-term potentiation-likefacilitation through GABA(A) receptor blockade in the mouse dentate gyrus invivo[J]. Neuroreport,2008,19(18):1809-1813
[13]刘永峰，闵苏，董军，等.异丙酚预先给药对抑郁大鼠电休克后海马Glu和GABA水平的影响[J].中华麻醉学杂志，2009，29(2)：121-124
[14] Zhang H, Wang W, Gao W, et al. Effect of propofol on the levels ofneurotransmitters in normal human brain: a magnetic resonance spectroscopystudy[J]. Neurosci Lett,2009,467(3):247-251
[15] Dong J, Min S, Wei K, et al. Effects of electroconvulsive therapy and propofolon spatial memory and glutamatergic system in hippocampus of depressed rats[J].J ECT,2010,26(2):126-130
[16] Yagmurdur H, Ayyildiz A, Karaguzel E, et al. Propofol reduces nitricoxide-induced apoptosis in testicular ischemia-reperfusion injury bydownregulating the expression of inducible nitric oxide synthase[J]. ActaAnaesthesiol Scand,2008,52(3):350-357
[17] Wang HY, Wang GL, Yu YH, et al. The role of phosphoinositide-3-kinase/Aktpathway in propofol-induced postconditioning against focal cerebralischemia-reperfusion injury in rats[J]. Brain Res,2009,1297(11):177-184
[18]董军，闵苏，魏珂，等.异丙酚联合电休克治疗对抑郁大鼠海马和纹状体谷氨酸含量的影响[J].中华麻醉学杂志，2008，28(8)：704-707
[19]刘永峰，闵苏，董军，等.无抽搐电休克治疗大鼠抑郁症与海马-氨基丁酸通路的关系[J].中国神经精神疾病杂志，2009，35(4)：238-241
[20]董军，闵苏，魏珂，等.无抽搐电休克治疗大鼠抑郁症的谷氨酸能机制研究[J].中国神经精神疾病杂志，2008，35(5)：310-312
[21]刘媛媛，闵苏，董军，等.无抽搐电休克对抑郁大鼠学习记忆功能的影响及其突触可塑性机制[J].中国神经精神疾病杂志，2010，36(2)：70-74
[22] Osiecka KM, Nieznanska H, Skowronek KJ, et al. Tau inhibits tubulinoligomerization induced by prion protein[J]. Biochim Biophys Acta,2010,1813(10):1845-1853
[23] De Calignon A, Fox LM, Pitstick R, et al. Caspase activation precedes and leadsto tangles[J]. Nature,2010,464(16):1201-1204
[24]李芳序，卢静，许亚杰，等.老年性痴呆发病过程中内源性甲醛慢性损伤机制[J].生物化学与生物物理进展，2008，35(4)：393-400
[25] Combs B, Voss K, Gamblin TC, et al. Pseudohyperphosphorylation hasdifferential effects on polymerization and function of tau isoforms[J].Biochemistry,2011,50(44):9446-9456
[26] Canu N, Filesi I, PristeràA, et al. Altered intracellular distribution of PrPC andimpairment of proteasome activity in Tau overexpressing cortical neurons[J]. JAlzheimers Dis,2011,27(3):603-613
[27] Kopeikina KJ, Carlson GA, Pitstick R, et al. Tau accumulation causesmitochondrial distribution deficits in neurons in a mouse model of tauopathy andin human Alzheimer's disease brain[J]. Am J Pathol,2011,179(4):2071-2082
[28] Sun Q, Gamblin TC. Pseudohyperphosphorylation causing AD-like changes intau has significant effects on its polymerization[J]. Biochemistry,2009,48(25):6002-6011
[29]刘付宁，曹铭辉，梁建军，等.急性吗啡暴露对大鼠前额叶皮质Tau蛋白磷酸化及学习记忆的影响[J].临床麻醉学杂志，2010，26(1)：61-63
[30] Blazquez-Llorca L, Garcia-Marin V, Merino-Serrais P, et al. Abnormal Tauphosphorylation in the thorny excrescences of CA3hippocampal neurons inpatients with Alzheimer's disease[J]. J Alzheimers Dis,2011,26(4):683-698
[31] Bibow S, Ozenne V, Biernat J, et al. Structural impact of proline-directedpseudophosphorylation at AT8, AT100, and PHF1epitopes on441-residue Tau[J].J Am Chem Soc,2011,133(40):15842-15845
[32]李洁颖，晏勇，蔡志友，等.胰岛素信号通路磷脂酰肌醇-3激酶/丝氨酸苏氨酸蛋白激酶对海马神经元β-淀粉样前体蛋白裂解酶1表达的影响[J].中华神经科杂志，2009，42(11)：737-741
[33] Wu FY, Feng Q, Cheng M, et al. The activation of excitatory amino acidreceptors is involved in tau phosphorylation induced by cold water stress[J]. ProgBiochem Biophys,2010,37(5):510-516
[34] Kingston S, Mao LM, Yang L, et al. Propofol inhibits phosphorylation ofN-methyl-D-aspartate receptor NR1subunits in neurons[J]. Anesthesiology,2006,104(4):736-739
[35]于布为，薛庆生，夏梦，等.异丙酚对大鼠脑片不同性质损伤的影响[J].中华医学杂志，2003，83(13)：1176-1179
[36]戴泽平，田玉科，汪辉，等.全凭静脉麻醉老龄大鼠海马tau蛋白磷酸化水平与认知功能的关系[J].临床麻醉学杂志，2008，24(3)：230-232
[2] Conrad MS, Richard A. The handbook for electroconvulsive therapy[M].California: Eagle Race Medical Technologies Company Press,1999,13-15
[3] Luo J, Min S, Wei K, et al. Propofol protects against impairment oflearning-memory and imbalance of hippocampal Glu/GABA induced byelectroconvulsive shock in depressed rats[J]. J Anesth,2011,25(5):657-665
[4] Andrade C, Singh NM, Thyagarajan S, et al. Possible glutamatergic and lipidsignalling mechanisms in ECT-induced retrograde amnesia: experimentalevidence for involvement of COX-2, and review of literature[J]. J Psychiatr Res,2008,42(10):837-850
[5] Dong J, Min S, Wei K, Li P, Cao J, Li Y.Effects of electroconvulsive therapy andpropofol on spatial memory and glutamatergic system in hippocampus ofdepressed rats[J]. J ECT,2010,26(2):126-130
[6] Kartalci S, Karabulut AB, Ozcan AC, et al. Acute and chronic effects ofelectroconvulsive treatment on oxidative parameters in schizophrenia patients[J].Prog Neuropsychopharmacol Biol Psychiatry,2011,35(7):1689-1694
[7] Kato N. Neurophysiological mechanisms of electroconvulsive therapy fordepression[J]. Neurosci Res,2009,64(1):3-11
[8] Cudalbu C, Lanz B, Duarte JM, Morgenthaler FD, Pilloud Y, Mlynárik V,Gruetter R. Cerebral glutamine metabolism under hyperammonemia determinedin vivo by localized (1)H and (15)NNMR spectroscopy[J]. J Cereb Blood FlowMetab,2011, DOI:10.1038/jcbfm.2011.173
[9] Kloda A, Martinac B, Adams DJ. Polymodal regulation of NMDA receptorchannels[J]. Channels (Austin),2007,1(5):334-343
[10] Allyson J, Dontigny E, Auberson Y, et a1. Blockade of NR2A-containingNMDA receptors induces Tau phosphorylation in rat hippocampal slices[J].Neural Plast,2010, DOI:10.1155/2010/340168
[11] Bardo S, Cavazzini MG, Emptage N. The role of the endoplasmic reticulum Ca2+store in the plasticity of central neurons[J]. Trends Pharmacol Sci,2006,27(2):78–84
[12]李玺，刘颖，张欣，等.人参皂苷Rg1对大鼠脑片AD模型磷酸化Tau蛋白及NMDA受体亚单位NR1，NR2B表达的影响[J].中国中药杂志，2010，35(24)：3339-3343
[13] MaláH, Chen Y, Worm VH. Cognitive enhancing effects of an AMPA receptorpositive modulator on place learning in mice[J]. Behav Brain Res,2012,226(1):18–25
[14] Dennis SH, Jaafari N, Cimarosti H, et al. Oxygen/glucose deprivation induces areduction in synaptic NMDA receptors on hippocampal CA3neurons mediatedby mGluR1and adenosine A3receptors[J]. J Neurosci,2011,31(33):11941-11952
[15] Vieira M, Fernandes J, Burgeiro, et al. Excitotoxicity through Ca2+-permeableNMDA receptors requires Ca2+-dependent JNK activation[J]. Neurobiol Dis,2010,40(3):645-655
[16] Nakamoto M, Nalavadi V, Epstein MP, et al. Fragile X mental retardation proteindeficiency leads to excessive mGluR5-dependent internalization of NMDAreceptors[J]. Proc Natl Acad Sci USA,2007,104(39):15537-15542
[17] Bliss RM, Finckbone VL, Trice J, et al. Tumor necrosis factor-α (TNF-α)augments NMDA-induced purkinje neuron toxicity[J]. Brain Res,2011,1836(1):1-14
[18] Shutter L, Tong KA, Holshouser BA. Proton MRS in acute traumatic brain injury:role for glutamate/glutamine and choline for outcome prediction[J]. JNeurotrauma,2004,21(12):1693-1705
[19] Liu Z, Li H, Zhang W, et al. Neuregulin-1β prevents Ca2+overloading andapoptosis through PI3K/Akt activation in cultured dorsal root ganglion neuronswith excitotoxicity induced by glutamate[J]. Cell Mol Neurobiol,2011,31(8):1195-1201
[20] Lehtihet M, Honkanen RE, Sj holm A. Glutamate inhibits protein phosphatasesand promotes insulin exocytosis in pancreatic beta-cells[J]. Biochem BiophysRes Commun,2005,328(2):601-607
[21] Bibow S, Ozenne V, Biernat J, et al. Structural impact of proline-directedpseudophosphorylation at AT8, AT100, and PHF1epitopes on441-residueTau[J]. J Am Chem Soc,2011,133(40):15842-15845
[22]李洁颖，晏勇，蔡志友，等.胰岛素信号通路磷脂酰肌醇-3激酶/丝氨酸苏氨酸蛋白激酶对海马神经元β-淀粉样前体蛋白裂解酶1表达的影响[J].中华神经科杂志，2009，42(11)：737-741
[23] Chin PC, Majdzadeh N, D'Mello SR. Inhibition of GSK3beta is a common eventin neuroprotection by different survival factors[J]. Brain Res Mol Brain Res,2005,137(1-2):193-201
[24] Wu FY, Feng Q, Cheng M, et al. The activation of excitatory amino acidreceptors is involved in tau phosphorylation induced by cold water stress[J].Prog Biochem Biophys,2010,37(5):510-516
[25] Petroni D, Tsai J, Mondal D, et al. Attenuation of low dose methylmercury andglutamate induced-cytotoxicity and tau phosphorylation by anN-methyl-D-aspartate antagonist in human neuroblastoma (SHSY5Y) cells[J].Environ Toxicol,2011, DOI:10.1002/tox.20765
[26] Vossel KA, Zhang K, Brodbeck J, et al. Tau reduction prevents abeta-induceddefects in axonal transport[J]. Science,2010,333(6001):198
[27] Sato S, Xu J, Okuyama S, et al. Spatial learning impairment, enhancedCDK5/p35activity, and downregulation of NMDA receptor expression intransgenic mice expressing tau-tubulin kinase1[J]. J Neurosci,2008,28(53):14511-14521
[28] Weingarten MD, Lockwood AH, Hwo SY, et al. A protein factor essential formicrotubule assembly[J]. Proc Natl Acad Sci USA,1975,72(5):1858-1862
[29] Cleveland DW, Hwo SY, Kirschner MW. Purification of Tau, amicrotubule-associated protein that induces assembly of microtubules frompurified tubulin[J]. J Mol Biol,1977,116(2):207-225
[30] Binder LI, Frankfurter A，Rebhun LI. The distribution of tau in the mammaliancentral nervous system[J]. J Cell Biol,1985,101(4):1371-1378
[31] Panda D, Goode BL, Feinstein SC, et al. Kinetic stabilization of microtubuledynamics at steady state by tau and microtubule-binding domains of tau[J].Bioehemistry,1995,34(35):11117-11127
[32] Osiecka KM, Nieznanska H, Skowronek KJ, et al. Tau inhibits tubulinoligomerization induced by prion protein[J]. Biochim Biophys Acta,2010,1813(10):1845-1853
[33] De Calignon A, Fox LM, Pitstick R, et al. Caspase activation precedes and leadsto tangles[J]. Nature2010,464(16):1201-1204
[34]王建枝，龚成新，I Grundke-Iqbal，等.阿尔茨海默病tau蛋白异常修饰与其功能的关系[J].生物化学与生物物理进展，1999，26(2)：154-157
[35] Naqvi SH，王维山，苗君叶，等.甲醛诱导Tau蛋白形成“孔道样”聚集结构[J].生物化学与生物物理进展，2010，37(11)：1195-1203
[36] Combs B, Voss K, Gamblin TC, et al. Pseudohyperphosphorylation hasdifferential effects on polymerization and function of tau isoforms[J].Biochemistry,2011,50(44):9446-9456
[37]李芳序，卢静，许亚杰，等.老年性痴呆发病过程中内源性甲醛慢性损伤机制[J].生物化学与生物物理进展，2008，35(4)：393-400
[38] Zhang B, Carroll J, Trojanowski JQ. The microtubule-stabilizing agent,epothilone d, reduces axonal dysfunction, neurotoxicity, cognitive deficits, andAlzheimer-like pathology in an interventional study with aged tau transgenicmice[J]. J Neurosci,2012,32(11):3601-3611
[39] McVicker DP, Chrin LR, Berger CL. The nucleotide-binding state ofmicrotubules modulates kinesin processivity and the ability of Tau to inhibitkinesin-mediated
[40] Giasson BI, Forman MS, Higuchi M, et al. Initiation and synergistic fibrillizationof tau and alpha-synuclein[J]. Science,2003,300(5619):636-640
[41] Onishi T, Iwashita H, Uno Y, et al. A novel glycogen synthase kinase-3inhibitor2-methyl-5-(3-{4-[(S)-methylsulfinyl]phenyl}-1-benzofuran-5-yl)-1,3,4-oxadiazole (MMBO) decreases Tau phosphorylation and amelioratescognitive deficits in a transgenic model of alzheimer's disease[J]. J Neurochem,2011,119(6):1330-1340
[42] Wang H, Zhao H, Ye Y, et al. Focal cerebral ischemia induces alzheimer'sdisease-like pathological change in rats[J]. J Huazhong Univ Sci Technolog MedSci,2010,30(1):29-36
[43] Carroll JC, Iba M, Bangasser DA, et al. Chronic stress exacerbates Tau pathology,neurodegeneration, and cognitive performance through a corticotropin-releasingfactor receptor-dependent mechanism in a transgenic mouse model oftauopathy[J]. J Neurosci,2011,31(40):14436-14449
[44] Kopeikina KJ, Carlson GA, Pitstick R, et al. Tau accumulation causesmitochondrial distribution deficits in neurons in a mouse model of tauopathy andin human Alzheimer's disease brain[J]. Am J Pathol,2011,179(4):2071-2082
[45] Liu SJ, Zhang AH, Li HL, et al. Overactivation of glycogen synthase kinase-3byinhibition of phosphoinositol-3kinase and protein kinase C leads tohyperphosphorylation of tau and impairment of spatial memory[J]. J Neurochem,2003,87(6):1333-1344
[46] Maurer K, Hoyer S. Alois Alzheimer revisited: differences in origin of thedisease carrying his name[J]. J Neural Transm2006;113(11):1645–1658
[47] Bulbarelli A, Lonati E, Cazzaniga E, et al. Pin1affects Tau phosphorylation inresponse to abeta oligomers[J]. Mol Cell Neurosci,2009,42(1):75-80
[48] Martin L, Magnaudeix A, Wilson CM, et al. The new indirubin derivativeinhibitors of glycogen synthase kinase-3,6-BIDECO and6-BIMYEO, preventtau phosphorylation and apoptosis induced by the inhibition of proteinphosphatase-2A by okadaic acid in cultured neurons[J]. J Neurosci Res,2011,89(11):1802-1811
[49] Sun Q, Gamblin TC. Pseudohyperphosphorylation causing AD-like changes intau has significant effects on its polymerization[J]. Biochemistry,2009,48(25):6002-6011
[50] Phiel CJ, Wilson CA, Lee VM, et al. GSK-3alpha regulates production ofAlzheimer's disease amyloid-beta peptides[J]. Nature,2003,423(6938):435-439
[51] Wang Q, Zhang JY, Liu SJ, et al. Overactivated mitogen-activated protein kinaseby anisomycin induces tau hyperphosphorylation[J]. Acta Psiologica Sinica,2008,60(4):485-491
[52] Fu ZQ, Yang Y, Song J, et al. LiCl attenuates thapsigargin-induced tauhyperphosphorylation by inhibiting GSK-3β in vivo and in vitro[J]. J AlzheimersDis,2010,21(4):1107-1117
[53] De Vos A, Anandhakumar J, Van den Brande J, et al. Yeast as a model system tostudy tau biology[J]. Int J Alzheimers Dis,2011, DOI:10.4061/2011/428970
[54] Kawakami F, Suzuki M, Shimada N, et al. Stimulatory effect of α-synuclein onthe tau-phosphorylation by GSK-3β[J]. FEBS J,2011,278(24):4895-4904
[55] Giese KP. GSK-3: a key player in neurodegeneration and memory[J]. IUBMBLife,2009,61(5):516-521
[56] Blazquez-Llorca L, Garcia-Marin V, Merino-Serrais P, et al. Abnormal Tauphosphorylation in the thorny excrescences of CA3hippocampal neurons inpatients with alzheimer's disease[J]. J Alzheimers Dis,2011,26(4):683-698
[57] Popkie AP, Zeidner LC, Albrecht AM, et al. Phosphatidylinositol3-kinase (PI3K)signaling via glycogen synthase kinase-3(Gsk-3) regulates DNA methylation ofimprinted loci[J]. J Biol Chem,2010,285(53):41337-41347
[58]郭建荣，岳云，崔健君，等.异丙酚对缺血再灌注损伤大鼠海马氨基酸递质水平变化及神经元凋亡的影响[J].病理生理学杂志，2007，23(8)：1547-1550
[59]曾育琦,陈晓春,黄春,等.人参皂苷Rgl通过调节GSK-13/PP2A活性减轻皮层神经元Tau蛋白过度磷酸化[J].解剖学报,2000，38(6)：665-670
[60] Liang Z, Liu F, Iqbal K, et al. Decrease of protein phosphatase2A and itsassociation with accumulation and hyperphosphorylation of tau in Downsyndrome[J]. J Alzheimers Dis,2008,13(3):295-320
[61] Zhang Y, Liang J, Sun L, et al. Inhibition of PP-2A and the consequent activationof JNK/c-Jun are involved in tributyltin-induced apoptosis in human amnioniccells[J]. Environ Toxicol,2011, doi:10.1002/tox.20730
[62]薛海波.阿尔茨海默病的神经心理学和神经化学诊断研究[Ｄ].上海交通大学，2006
[63]中华医学会神经病学分会痴呆与认知障碍学组写作组.血管性认知障碍诊治指南，中华神经科杂志，2011，44(2)：142-147
[64] Jia JP, Meng R, Sun YX, et al. Cerebrospinal fluid tau, Abetal-42andinflammatory cytokines in patients with Alzheimer's disease and vasculardementia[J]. Neurosci Lett,2005,383:12-16
[65] Stefani A, Bernardini S, Panella M, et al. AD with subcortical white matterlesions and vascular dementia: CSF markers for differential diagnosis[J]. JNeurol Sci,2005,237:83-88
[66] Hans P, Bonhomme V, Collette J, et al. Propofol protects cultured rathippocampal neurons against N-methyl-D-aspartate receptor-mediated glutamatetoxicity[J]. J Neurosurg Anesthesiol,1994,6(4):249-253
[67] Kingston S, Mao LM, Yang L, et al. Propofol inhibits phosphorylation ofN-methyl-D-aspartate receptor NR1subunits in neurons[J]. Anesthesiology,2006,104(4):736-739
[68] Dong J, Min S, Wei K, Li P, Cao J, Li Y.Effects of electroconvulsive therapy andpropofol on spatial memory and glutamatergic system in hippocampus ofdepressed rats[J]. J ECT,2010,26(2):126-130
[69] Yagmurdur H, Ayyildiz A, Karaguzel E, et al. Propofol reduces nitricoxide-induced apoptosis in testicular ischemia-reperfusion injury bydownregulating the expression of inducible nitric oxide synthase[J]. ActaAnaesthesiol Scand,2008,52(3):350-357
[70] Wang B, Shravah J, Luo H, et al. Propofol protects against hydrogenperoxide-induced injury in cardiac H9c2cells via Akt activation and Bcl-2up-regulation[J]. Biochem Biophys Res Commun,2009,389(1):105-111
[71] Xi HJ, Zhang TH, Tao T, et al. Propofol improved neurobehavioral outcome ofcerebral ischemia-reperfusion rats by regulating Bcl-2and Bax expression[J].Brain Res,2011,1410:24-32
[72] Fang F, Chen X, Huang T, et al. Multi-faced neuroprotective effects ofginsenoside Rg1in an Alzheimer mouse model[J]. Biochim Biophys Acta,2011,1822(2):286-292
[73] Jiang B, Xiong Z, Yang J, et al. Antidepressant-like effects of ginsenosideRg1produced by activation of BDNF signaling pathway and neurogenesis in thehippocampus[J]. Br J Pharmacol,2012, doi:10.1111/j.1476-5381.2012.01902.x
[74]褚燕琦，张兰，李玮，等.人参皂苷对蛋白磷酸酶抑制剂冈田酸拟阿尔采末病细胞模型的影响[J].中国药理学通报，2008，24(7)：879-884
[75] Wang YZ, Chen J, Chu SF, et al. Improvement of memory in mice and increaseof hippocampal excitability in rats by ginsenoside Rg1's metabolites ginsenosideRh1and protopanaxatriol[J]. J Pharmacol Sci,2009,109(4):504-510
[76] Zhao L, Wang F, Gui B, et al. Prophylactic lithium alleviates postoperativecognition impairment by phosphorylating hippocampal glycogen synthasekinase-3β (Ser9) in aged rats[J]. Exp Gerontol,2011,46(12):1031-1036
[77]陆文惠，屈秋民，曹红梅，等.锂对慢性铝暴露大鼠脑内CDK5和PP2A表达的影响[J].西安交通大学学报(医学版)，2010，31(4)：463-466
[78] Ponce-Lopez T, Liy-Salmeron G, Hong E, et al. Lithium, phenserine, memantineand pioglitazone reverse memory deficit and restore phospho-GSK3β decreasedin hippocampus in intracerebroventricular streptozotocin induced memorydeficitmodel[J]. Brain Res,2011,2046:73-85
[79]谭文斐，田阿勇，王俊科，等.氯化锂对脾切除大鼠海马Tau蛋白的影响[J].中国药理学通报，2010，26(11)：1526-1527
[80] Wada A, Yokoo H, Yanagita T, et al. L ithium: Potential therapeutics against acutebrain injuries and chronic neurodegenerative diseases[J]. J Pharmacol Sci,2005,99∶307-321
[81] Li X, Lu F, Tian Q, et al. Activation of glycogen synthase kinase-3inducesAlzheimer-like tau hyperphosphorylation in rat hippocampus slices in culture[J].J Neural Transm,2006,113:93-102
[82] Zhang C, Du F, Shi M, et al. Ginsenoside Rd protects neurons againstglutamate-induced excitotoxicity by inhibiting Ca(2+) influx[J]. Cell MolNeurobiol,2012,32(1):121-128
[83] Chen Z, Lu T, Yue X, et al. Neuroprotective effect of ginsenoside Rb1onglutamate-induced neurotoxicity: with emphasis on autophagy[J]. Neurosci Lett,2010,482(3):264-268
[84] Li XY, Liang J, Tang YB, et al. Ginsenoside Rd prevents glutamate-inducedapoptosis in rat cortical neurons[J]. Clin Exp Pharmacol Physiol,2010,37(2):199-204
[85] Kandel ER.The moleeular biology of memory storage: a dialogue between genesand synapses[J]. Sience,2001,294(5544):1030-1038
[86]于萍，袁水霞，李霞，等.记忆过程中海马CA1区神经元的集群放电特征[J].心理学报，2011，43(8)：917-928
[87]倪兵，钱晨灿，吴睿洁，等.海马参与工作记忆目标匹配增强及其时间过程—基于颅内脑电的研究[J].生物化学与生物物理进展，2011，38(11)：1027-1035
[88] Choi BR, Kwon KJ, Park SH, et al. Alternations of septal-hippocampal system inthe adult wistar rat with spatial memory impairments induced by chroniccerebral hypoperfusion[J]. Exp Neurobiol,2011,20(2):92-99
[89] Preissmann D, Bertholet L, Sierro G, et al. Accurate performance of a rat modelof schizophrenia in the water maze depends on visual cue availability andstability: a distortion in cognitive mapping abilities?[J]. Behav Brain Res,2011,223(1):145-153
[90] Nishida Y, Yokotat, Takaijashit, etal. Deletion of vitamin E enhanees phenotypeof Alzheimer disease model mouse[J]. Bioehem Biophys Res Commun,2006,350(3):530-536
[91] Wu QY, Li J, Feng ZT, et al. Bone marrow stromal cells of transgenic mice canimprove the cognitive ability of an AIZheimer,s disease rat model[J]. NeurosciLett,2007,417(3):281-285
[92] Harvey BH, Naciti C, Brand L, et al. Endocrine, eognitiveand hippocampal/cortical5HT1A/2A receptor changes evoked by a time-dependent sensitization(TDS) stress model in rats[J]. BrainRes,2003,983(l-2):97-107
[93] Nicholasa, Mijnhozcd, Fergusond E，et al. Enhancing cognition after stress withgene therapy[J]. J Neurosci,2006,26(45):11637-11643
[1] Michael H, Ebert. Current diagnosis and treatment psychiatry[M].2th ed. NewYork: Mc Graw-Hill Press,2008,306-307
[2] Conrad MS, Richard A. The handbook for electroconvulsive therapy[M].California: Eagle Race Medical Technologies Company Press,1999,13-15
[3] Luo J, Min S, Wei K, et al. Propofol protects against impairment oflearning-memory and imbalance of hippocampal Glu/GABA induced byelectroconvulsive shock in depressed rats[J]. J Anesth,2011,25(5):657-665
[4] Andrade C, Singh NM, Thyagarajan S, et al. Possible glutamatergic and lipidsignalling mechanisms in ECT-induced retrograde amnesia: experimental evidencefor involvement of COX-2, and review of literature[J]. J Psychiatr Res,2008,42(10):837-850
[5] Dong J, Min S, Wei K, et al. Effects of electroconvulsive therapy and propofol onspatial memory and glutamatergic system in hippocampus of depressed rats[J]. JECT,2010,26(2):126-130
[6] Kartalci S, Karabulut AB, Ozcan AC, et al. Acute and chronic effects ofelectroconvulsive treatment on oxidative parameters in schizophrenia patients[J].Prog Neuropsychopharmacol Biol Psychiatry,2011,35(7):1689-1694
[7] Kato N. Neurophysiological mechanisms of electroconvulsive therapy fordepression[J]. Neurosci Res,2009,64(1):3-11
[8] Kloda A, Martinac B, Adams DJ. Polymodal regulation of NMDA receptorchannels[J]. Channels (Austin),2007,1(5):334-343
[9] Dennis SH, Jaafari N, Cimarosti H, et al. Oxygen/glucose deprivation induces areduction in synaptic NMDA receptors on hippocampal CA3neurons mediated bymGluR1and adenosine A3receptors[J]. J Neurosci,2011,31(33):11941-11952
[10] Vieira M, Fernandes J, Burgeiro, et al. Excitotoxicity through Ca2+-permeableNMDA receptors requires Ca2+-dependent JNK activation[J]. Neurobiol Dis,2010,40(3):645-655
[11] Bliss RM, Finckbone VL, Trice J, et al. Tumor necrosis factor-α (TNF-α)augments NMDA-induced Purkinje neuron toxicity[J]. Brain Res,2011,1836(1):1-14
[12] Shutter L, Tong KA, Holshouser BA. Proton MRS in acute traumatic brain injury:role for glutamate/glutamine and choline for outcome prediction[J]. JNeurotrauma,2004,21(12):1693-1705
[13] Wu FY, Feng Q, Cheng M, et al. The activation of excitatory amino acidreceptors is involved in tau phosphorylation induced by cold water stress[J]. ProgBiochem Biophys,2010,37(5):510-516
[14] Petroni D, Tsai J, Mondal D, et al. Attenuation of low dose methylmercury andglutamate induced-cytotoxicity and tau phosphorylation by anN-methyl-D-aspartate antagonist in human neuroblastoma (SHSY5Y) cells[J].Environ Toxicol,2011, DOI:10.1002/tox.20765
[15] Weingarten MD, Lockwood AH, Hwo SY, et al. A protein factor essential formicrotubule assembly[J]. Proc Natl Acad Sci USA,1975,72(5):1858-1862
[16] Osiecka KM, Nieznanska H, Skowronek KJ, et al. Tau inhibits tubulinoligomerization induced by prion protein[J]. Biochim Biophys Acta,2010,1813(10):1845-1853
[17] Cleveland DW, Hwo SY, Kirschner MW. Purification of Tau, a microtubule-associated protein that induces assembly of microtubules from purified tubulin[J].J Mol Biol,1977,116(2):207-225
[18] De Calignon A, Fox LM, Pitstick R, et al. Caspase activation precedes and leadsto tangles[J]. Nature2010,464(16):1201-1204
[19] Combs B, Voss K, Gamblin TC, et al. Pseudohyperphosphorylation hasdifferential effects on polymerization and function of tau isoforms[J].Biochemistry,2011,50(44):9446-9456
[20] Canu N, Filesi I, PristeràA, et al. Altered intracellular distribution of PrPC andimpairment of proteasome activity in Tau overexpressing cortical neurons[J]. JAlzheimers Dis,2011,27(3):603-613
[21] Onishi T, Iwashita H, Uno Y, et al. A novel glycogen synthase kinase-3inhibitor2-methyl-5-(3-{4-[(S)-methylsulfinyl]phenyl}-1-benzofuran-5-yl)-1,3,4-oxadiazole (MMBO) decreases Tau phosphorylation and ameliorates cognitivedeficits in a transgenic model of alzheimer's disease[J]. J Neurochem,2011, DOI:10.1111/j.1471-4159.2011.07532.x
[22] Kopeikina KJ, Carlson GA, Pitstick R, et al. Tau accumulation causesmitochondrial distribution deficits in neurons in a mouse model of tauopathy andin human Alzheimer's disease brain[J]. Am J Pathol,2011,179(4):2071-2082
[23] Wang Q, Zhang JY, Liu SJ, et al. Overactivated mitogen-activated protein kinaseby anisomycin induces tau hyperphosphorylation[J]. Acta Psiologica Sinica,2008,60(4):485-491
[24] Fu ZQ, Yang Y, Song J, et al. LiCl attenuates thapsigargin-induced tauhyperphosphorylation by inhibiting GSK-3β in vivo and in vitro[J]. J AlzheimersDis,2010,21(4):1107-1117
[25] De Vos A, Anandhakumar J, Van den Brande J, et al. Yeast as a model system tostudy tau biology[J]. Int J Alzheimers Dis,2011, DOI:10.4061/2011/428970
[26] Blazquez-Llorca L, Garcia-Marin V, Merino-Serrais P, et al. Abnormal Tauphosphorylation in the thorny excrescences of CA3hippocampal neurons inpatients with alzheimer's disease[J]. J Alzheimers Dis,2011,26(4):683-698
[27] Bibow S, Ozenne V, Biernat J, et al. Structural impact of proline-directedpseudophosphorylation at AT8, AT100, and PHF1epitopes on441-residue Tau[J].J Am Chem Soc,2011,133(40):15842-15845
[28] Ray P, Kar A, Fushimi K, et al. PSF suppresses Tau exon10inclusion byinteracting with a stem-loop structure downstream of exon10[J]. J Mol Neurosci,2008,45(3):453-466
[29] Bibow S, Mukrasch MD, Chinnathambi S, et al. The dynamic structure offilamentous Tau[J]. Angew Chem Int Ed Engl,2011, DOI:10.1002/anie.201105493
[30] Chin PC, Majdzadeh N, D'Mello SR. Inhibition of GSK3beta is a common eventin neuroprotection by different survival factors[J]. Brain Res Mol Brain Res,2005,137(1-2):193-201
[31] Lehtihet M, Honkanen RE, Sj holm A. Glutamate inhibits protein phosphatasesand promotes insulin exocytosis in pancreatic beta-cells[J]. Biochem Biophys ResCommun,2005,328(2):601-607
[32] Kingston S, Mao LM, Yang L, et al. Propofol inhibits phosphorylation ofN-methyl-D-aspartate receptor NR1subunits in neurons[J]. Anesthesiology,2006,104(4):736-739
[33] Hans P, Bonhomme V, Collette J, et al. Propofol protects cultured rathippocampal neurons against N-methyl-D-aspartate receptor-mediated glutamatetoxicity[J]. J Neurosurg Anesthesiol,1994,6(4):249-253
[34] Fang F, Chen X, Huang T, et al. Multi-faced neuroprotective effects ofginsenoside Rg1in an Alzheimer mouse model[J]. Biochim Biophys Acta,2011,1822(2):286-292
[35] Zhao L, Wang F, Gui B, et al. Prophylactic lithium alleviates postoperativecognition impairment by phosphorylating hippocampal glycogen synthasekinase-3β (Ser9) in aged rats[J]. Exp Gerontol,2011,46(12):1031-1036
[36] Tasset I, Medina FJ, Pena J, et al. Olfactory bulberctomy induced oxidative andcell damage in rat: protective effect of melatoni[J]. Physiol Res,2010,59(2):105-112
[37] Will CC, Aird F, Redei EE. Selectively bred Wistar-Kyoto rats: an animal modelof depression and hyper-responsiveness toantidepressants[J]. Mol Psychiatry,2003,8(11):925-932
[38] Tejani-Butt S, Kluczynski J, ParéWP. Strain-dependent modification of behaviorfollowing antidepressant treatment[J]. Prog Neuropsychopharmacol BiolPsychiatry,2003,27(1):7-14
[39] Mutlu O, Ulak G, Celikyurt IK, et al. Effects of olanzapine, sertindole andclozapine on learning and memory in the Morris water maze test in naive andMK-801-treated mice[J]. Pharmacol Biochem Behav,2011,98(3):398-404
[40] Barat SA, Abdel-Rahman MS. Decreased cocaine and lidocaine-induced seizureresponse by dextromethorphan and DNQX in rat[J]. Brain Res,2011,756(1-2):179-183
[41] Altar CA, Laeng P, Jurata LW, et al. Electroconvulsive seizures regulate geneexpression of distinct neurotrophic signaling pathways[J]. J Neuresci,2004,24(11):2667-2677
[42] Wang D, Noda Y, Tsunekawa H, et al. Bshavioural and neurochemical feaures ofolfactory bulbertomized rats resembling depression with co-morbid anixiety[J].Behav Brain Res,2007,178(2):262-273
[43] Kato S, Kito Y, Hemmi H, et al. Simultaneous determination of D-amino acidsby the coupling method of D-amino acid oxidase with high-performance liquidchromatography[J]. J Chromatogr B Analyt Technol Biomed Life Sci,2011,879(29):3190-3195
[44] Choi BR, Kwon KJ, Park SH, et al. Alternations of septal-hippocampal system inthe adult Wistar rat with spatial Memory impairments induced by chronic cerebralhypoperfusion[J]. Exp Neurobiol,2011,20(2):92-99
[45] Preissmann D, Bertholet L, Sierro G, et al. Accurate performance of a rat modelof schizophrenia in the water maze depends on visual cue availability andstability: a distortion in cognitive mapping abilities?[J]. Behav Brain Res,2011,223(1):145-153
[46] Carroll JC, Iba M, Bangasser DA, et al. Chronic stress exacerbates Tau pathology,neurodegeneration, and cognitive performance through a corticotropin-releasingfactor receptor-dependent mechanism in a transgenic mouse model ofTauopathy[J]. J Neurosci,2011,31(40):14436-14449
[47] Palmio J, Huuhka M, Laine S, et al. Electroconvulsive therapy and biomarkers ofneuronal injury and plasticity: serum levels of neuron-specific enolase andS-100b protein[J]. Psychiatry Res,2010,177(1-2):97-100
[48] Stover JF, Kempski OS. Anesthesia increases circulating glutamate inneurosurgical patients[J]. Acta Neurochir (Wien),2005,147(8):847-853
[49] Feiner JR, Bickler PE, Estrada S, et al. Mild hypothermia, but not propofol, isneuroprotective in organotypic hippocampal cultures[J]. Anesth Analg,2005,100(1):215-225
[50] Li KY, Guan YZ, Krnjevi K, et al. Propofol facilitates glutamatergictransmission to neurons of the ventrolateral preoptic nucleus[J]. Anesthesiology,2009,111(6):1271-1278
[51] Pesi V, Milanovi D, Tani N, et al. Potential mechanism of cell death in thedeveloping rat brain induced by propofol anesthesia[J]. Int J Dev Neurosci,2009,27(3):279-287
[52] Nie CL, Wang XS, Liu Y, et al. Amyloid-like aggregates of neuronal tau inducedby formaldehyde promote apoptosis of neuronal cells[J]. BMC Neuroscience,2007,23(8):9
[53] Yao Z, Guo Z, Yang C, et al. Phenylbutyric acid prevents rats fromelectroconvulsion-induced memory deficit with alterations of memory-relatedproteins and tau hyperphosphorylation[J]. Neuroscience,2010,168(2):405-415
[54] Bulbarelli A, Lonati E, Cazzaniga E, et al. Pin1affects Tau phosphorylation inresponse to Abeta oligomers[J]. Mol Cell Neurosci,2009,42(1):75-80
[55] Tan W, Cao X, Wang J, et a1. Tau hyperphosphorylation is associated withmemory impairment after exposure to1.5%isoflurane without temperaturemaintenance in rats[J]. Eur J Anaesthesiol,2010,27(9):835-841
[56] Vossel KA, Zhang K, Brodbeck J, et al. Tau reduction prevents Abeta-induceddefects in axonal transport[J]. Science,2010,333(6001):198
[57] Allyson J, Dontigny E, Auberson Y, et a1. Blockade of NR2A-containingNMDA receptors induces Tau phosphorylation in rat hippocampal slices[J].Neural Plast,2010, DOI:10.1155/2010/340168
[58] Sato S, Xu J, Okuyama S, et a1. Spatial learning impairment, enhancedCDK5/p35activity, and downregulation of NMDA receptor expression intransgenic mice expressing tau-tubulin kinase1[J]. J Neurosci,2008,28(53):14511-14521
[59] Muyllaert D, Kremer A, Jaworski T, et a1. Glycogen synthase kinase-3beta, or alink between amyloid and tan pathology[J]. Genes Brain Behav,2008,7(Suppl1):57-66
[60] Xu JJ, Wang YL. Propofol attenuation of hydrogen peroxide-mediated oxidativestress and apoptosis in cultured cardiomyocytes involves haeme oxygenase-1[J].Eur J Anaesthesiol,2008,25(5):395-402
[61] Straiko MM, Young C, Cattano D, et a1. Lithium protects againstanesthesia-induced developmental neuroapoptosis[J]. Anesthesiology,2009,110(4):862-868
[62] Klein RC, Warder SE, Galdzicki Z, et al. Kinetic and mechanisticcharacterization of NMDA receptor antagonism by replacement and truncationvariants of the conantokin peptides[J]. Neuropharmacology,2001,41(7):801-810
[63] Amadoro G, Ciotti MT, Costanzi M, et al. NMDA receptor mediates tau-inducedneurotoxicity by calpain and ERK/MAPK activation[J]. Proc Natl Acad Sci USA,2006,103(8):2892-2897
[64] Paterlini M, Valerio A, Baruzzi F, et a1. Opposing regulation of protein Taulevels by ionotropic and metabotropic glutamate receptors in human NT2neurons[J]. Neurosci Lett,1998,243(1-3):77-80
[65] Elyaman W, Terro F, Wong NS, et a1. In vivo activation and nucleartranslocation of phosphorylated glycogen synthase kinase-3beta in neuronalapoptosis: links to tau phosphorylation[J]. Eur J Neurosci,2002,15(4):651-660
[1] Weingarten MD, Lockwood AH, How SY, et al. A protein factor essential formicrolubule assembly[J]. Proc Nall Acard Sci USA,1975,72(5):1858-1862
[2] Cleveland DW, Hwo SY, Kirschner MW. Purification of Tau, a microtubuleassociated protein that induces assembly of microtubules from purified tubulin[J]. JMol Biol1977,116(2):207-725
[3] Hasegawa M. Biochemistry and molecular biology of Tauopathies[J].Neuropathology,2006,26(5):484-490
[4]王海均，赵洪洋，熊南翔，等.局灶性脑缺血再灌注致大鼠大脑皮质Tau蛋白异常高度磷酸化[J].华中科技大学学报(医学版)，2009，38(6)：739-743.
[5] Santacruz K, Lewis J, Spires T, et a1. Tau suppression in a neurode-generativemouse model improves memory function[J]. Science,2005,309(5733):476-481
[6]曲梅花，李辉，徐艳娟，等.人神经Tau蛋白与DNA相互作用[J].生物化学与生物物理进展，2004，31(10)：918-923
[7]盛之玲，曲梅花，何海进，等. HeLa、HEK293、SH-SY5Y细胞中的Tau蛋白[J].生物化学与生物物理进展,2008,35(12):1364-1370
[8]胡蜀红，杨雁，张建华，等.罗格列酮改善胰岛素抵抗大鼠海马Alzheimer病样Tau蛋白磷酸化水平[J].生物化学与生物物理进展，2007，34(5)：533-537
[9]苏衍萍，杜长青，王慧，等.中药髓复康对恒河猴脊髓半切后S-100、Tau蛋白表达的影响[J].解剖学杂志，2009，32(6)：778-780，784
[10] Williams DR. Tauopathies: classification and clinical update on neurodegenerativediseases associated with microtubule·associated protein Tau[J]. Intern Med J,2006,36(10):652-660
[11]张杰文，卢芬，李旭，等.叶酸和维生素B2对老年大鼠海马中Tau蛋白磷酸化的影响[J].中华神经科杂志，2007，40(1)：39-42
[12] Iqbal K, Alonso AD, Chen S, et al. Tau pathology in Alzheim erdisease and otherTauopathies[J]. Biochim Biophys Acta,2005,1739(2-3):198-210
[13]李琪，冯利杰，王海萍，等. tau蛋白的过度表达对非神经源细胞生长与分化的影响[J].中国药理学通报，2008，24(3)：365-369
[14]孙爱民，王海萍，沈玉君，等. Ser202/Thr205位点磷酸化Tau在神经元中的定位[J].中国药理学通报，2011，27(1)：41-45
[15]王鹏军，张昱，冯加纯，等. IGF-1对Aβ25-35致PC12细胞损伤的保护作用及其机制的探讨[J].中国老年学杂志，2007，27(2)：331-333
[16]张晓洁，杨雁，张木勋.1型糖尿病大鼠海马Alzheimer样磷酸酯酶2A活性降低导致Tau蛋白过度磷酸化[J].华中科技大学学报(医学版)，2009，38(1)：31-35
[17] Walton JR. An aluminum-based rat model for Alzheimer’s disease exhibitsoxidative damage inhibition of PP2A activity, hyperphosphorylated Tau andgranulovacular degeneration[J]. J Inorg Biochem,2007,101(9):1275-1284
[18]张晓洁，杨思思，张木勋，等.2型糖尿病与阿尔茨海默病互为发病风险的机制探讨[J].中国病理生理杂志，2010，26(6)：1107-1114
[19]李永坤，陈晓春，朱元贵，等.冈田酸诱导大鼠海马神经元Tau蛋白过度磷酸化[J].解剖学报，2005，36(3)：231-236
[20] Li HL, Wang SH, Lai XM, et al. Transfection with GSK-β in vivo induces Tauhyperphosphorylation at PHF-1site[J]. Chinese Journal ofPathophysiology,2006,22(3):506-510
[20]宋锦秋，陈晓春，张静，等.凝聚态Aβ25-35可通过JNK/p38MAPK途径诱导胎鼠皮层神经元Tau蛋白过度磷酸化[J].解剖学报，2007，38(5)：533-536
[21] Wang Q, Zhang JY, Liu SJ, et al. Overactivated mitogen-activated protein kinaseby anisomycin induces Tau hyperphosphorylation[J]. Acta Psiologica Sinica,2008,60(4):485-491
[22] Beurei E, Blivet-Van EM, Kornprobst M, et a1. Glycogen synthasc kinase-3inhibitors augment TRAIL induced apoptotic death in human hepatoma ce1ls[J].Biochemical Pharmacology,2009,77:54-65
[23] Sehafer BA, Bertram L, Miller BL, et a1. Association of GSK3B with Alzheimerdisease and frontotemporal dementia[J]. Arch Neurol,2008,65(10):1368-1374
[24]王海均，赵洪洋，熊南翔，等.局灶性脑缺血再灌注致大鼠大脑皮质Tau蛋白异常高度磷酸化[J].华中科技大学学报(医学版)，2009，38(6)：739-743
[25] Giese KP. GSK-3: a key player in neu rodegeneration and m emory[J]. IUBMBLife,2009,61(5):516-521
[26] Sun Q, Gamb lin TC. Pseudohyperphosphory lat ion caus ing AD-like changes inTau has sign if icant effects on its polym erizat ion[J]. Biochemistry,2009,48(25):6002-6011
[27] Qian W, Shi J, Liu F, et a1. PP2A regulates tan phosphorylation directly and alsoindirectly via activating GSK-3beta[J]. J Ahheimers DIS,2009,19(4):1221-1229
[28]刘飞，施建华，丁绍红，等.糖元合成酶激酶3β对微管相关蛋白Tau的磷酸化作用[J].生物化学与生物物理进展，2007，34(9)：945-951
[29] Muyllaert D, Kremer A, Jaworski T, et a1. Glycogen synthase kinase-3beta, or alink between amyloid and tan pathology[J]. Genes Brain Behav,2008,7(Suppl1):57-66
[30] Park YJ, Jang YM, Kwon YH. Isoflavones prevent endoplasmic reticulumstress-mediated neuronal degeneration by inhibiting Tau hyperphosphorylation inSH2SY5Y cells[J]. J Med Food,2009,12(3):528-535
[31]王鹏军，尚宏，宋荣蓉，等. MCI-186减轻Aβ1-40诱导PC12细胞Tau蛋白磷酸化的研究[J].中国老年学杂志，2009，29(20)：2624-2627
[32] Utreras E, Maccioni R, Gonza lez-Billault C. Cycl in-dependent kinase5activator p35over expression and amy loid beta synergism in crease apoptos is incu ltured neuronal cells[J]. Neuroscience,2009,161(4):978-987
[33] Deters N, Ittner LM, G tz J. Substrate specific reduction of PP2A activityexaggerates Tau pathology[J]. Biochem Biophys Res Commun,2009,379(2):400-405
[33] Bulbarlli A, Lonti E, Cazzaniga E, et al. Pin1affects Tau phosphorylation inresponse to Abeta oligomers[J]. Mol Cell Neurosci,2009,4(1):75-80
[34] Lim J, BalastikM, Lee TH, et al. Pin1has opposite effects on wild type andP301L Tau stab ility and Tauopathy[J]. J C lin Invest,2008,118(5):1877-1889
[35] Tortosa E, Santa-Maria I, Moreno F, et al. Binding of Hsp90to Tau promotes aconform ational change and aggregat ion of protein Tau[J]. J Alzheimers Dis,2009,17(2):319-325
[36] Wang JZ, Lira F. Miemtubule-associated protein Tau in development,degeneration and protection of neurons[J]. Progress in NeurobiologY,2008,85(2):148-175
[37]褚燕琦，张兰，李玮，等.人参皂苷对蛋白磷酸酶抑制剂冈田酸拟阿尔采末病细胞模型的影响[J].中国药理学通报，2008，24(7)：879-884
[38]王群，胡志红，王建枝，等.反复饥饿对大鼠空间学习及海马神经元骨架蛋白磷酸化的影响[J].中国生物化学与分子生物学报，2010，26(11)：1023-1027
[40] Reynolds CH, Garwood CJ, Wray S, et al. Phosphoryla ion regulates Tau interactions with Src homology3domains of phosphatidy linositol3-kinase,phospholipase Cgamma1, Grb2, and Src family kinase[J]. J Biol Chem,2008,283(26):18177-18186
[41] Sergeant N, Bretteville A, Hamdane M, et a1. Biochemistry of tall in Alzheimer,sdisease and related neurologieal disorders[J]. Expert Rev Proteomies,2008,5(2):207-241
[42]邓娟，周华东，李敬诚，等.吸烟对AD大鼠认知功能和Tau蛋白异常磷酸化的影响[J].中国行为医学科学，2007，16(7)：591-593
[43]杨江勇，顾建兰，施建华，等. O-GlcNAc糖基转移酶(OGT)基因表达的抑制对Tau蛋白磷酸化作用的影响[J].生物化学与生物物理进展，2009，6(3)：346-352
[44]汪建华，王学峰，龚云，等.耐药性癫痫患者术后脑组织中Tau蛋白的表达[J].中华神经科杂志，2005，38(9)：665-670
[45]段萍，李夏春，邓艳秋，等. Caspase-3对磷酸化Tau蛋白截断作用的研究[J].生物化学与生物物理进展，2010，32(1)：81-85
[50] Alix de C, Leora MF, Rose P, et a1. Caspase activation precedes and leads totangles[J]. Nature,2010,464(16):1201-1204
[51]盛之玲，刘延英，陈岚，等.非酶糖基化对α-synuclein分子构象的影响[J].生物化学与生物物理进展，2008，35(10)：1202-1208
[52]李芳序，卢静，许亚杰，等.老年性痴呆发病过程中内源性甲醛慢性损伤机制[J].生物化学与生物物理进展，2008，35(4)：393-400
[1] Andrade C, Singh NM, Thyagarajan S, et a1. Possible glutamatergic and lipidsignalling mechanisms in ECT-induced retrograde amnesia: experimental evidencefor involvement of COX-2, and review ofliterature[J]. J Psychiatr Res,2008,42(10):837-850
[2]何永光，王祖承，王飙，等.无抽搐电休克治疗抑郁症患者前后的听觉P300对照研究[J].上海精神医学，2008，20(1)：36-37,64
[3]何开华，闵苏.异丙酚在无抽搐电休克治疗中镇静的效果评价[J].重庆医科大学学报，2007，32(1)：65-66,85
[4] Butterfield NN, Graf P, Macleod BA, et al. Propofol reduces cognitive impairmentafter electroconvulsive therapy[J]. J ECT,2004,20(1):3-9
[5]黎平，闵苏，魏珂，等.异丙酚联合电休克治疗对抑郁大鼠行为学和学习记忆功能的影响[J].中华麻醉学杂志，2007，27(10)：940-943
[6] Dennis SH, Jaafari N, Cimarosti H, et al. Oxygen/glucose deprivation induces areduction in synaptic AMPA receptors on hippocampal CA3neurons mediated bymGluR1and adenosine A3receptors[J]. J Neurosci,2011,31(33):11941-11952
[7] Vieira M, Fernandes J, Burgeiro, et al. Excitotoxicity through Ca2+-permeableNMDA receptors requires Ca2+-dependent JNK activation[J]. Neurobiol Dis,2010,40(3):645-655
[8] Bliss RM, Finckbone VL, Trice J, et al. Tumor necrosis factor-α (TNF-α)augments NMDA-induced Purkinje neuron toxicity[J]. Brain Res,2011,1836(1):1-14
[9] Luo J, Min S, Wei K, et al. Propofol protects against impairment oflearning-memory and imbalance of hippocampal Glu/GABA induced byelectroconvulsive shock in depressed rats[J]. J Anesth,2011,25(5):657-665
[10] Kartalci S, Karabulut AB, Ozcan AC, et al. Acute and chronic effects ofelectroconvulsive treatment on oxidative parameters in schizophrenia patients[J].Prog Neuropsychopharmacol Biol Psychiatry,2011,35(7):1689-1694
[11] Kato N. Neurophysiological mechanisms of electroconvulsive therapy fordepression[J]. Neurosci Res,2009,64(1):3-11
[12] Matsuyama, S; Taniguchi, T; Kadoyama, K. et al. Long-term potentiation-likefacilitation through GABA(A) receptor blockade in the mouse dentate gyrus invivo[J]. Neuroreport,2008,19(18):1809-1813
[13]刘永峰，闵苏，董军，等.异丙酚预先给药对抑郁大鼠电休克后海马Glu和GABA水平的影响[J].中华麻醉学杂志，2009，29(2)：121-124
[14] Zhang H, Wang W, Gao W, et al. Effect of propofol on the levels ofneurotransmitters in normal human brain: a magnetic resonance spectroscopystudy[J]. Neurosci Lett,2009,467(3):247-251
[15] Dong J, Min S, Wei K, et al. Effects of electroconvulsive therapy and propofolon spatial memory and glutamatergic system in hippocampus of depressed rats[J].J ECT,2010,26(2):126-130
[16] Yagmurdur H, Ayyildiz A, Karaguzel E, et al. Propofol reduces nitricoxide-induced apoptosis in testicular ischemia-reperfusion injury bydownregulating the expression of inducible nitric oxide synthase[J]. ActaAnaesthesiol Scand,2008,52(3):350-357
[17] Wang HY, Wang GL, Yu YH, et al. The role of phosphoinositide-3-kinase/Aktpathway in propofol-induced postconditioning against focal cerebralischemia-reperfusion injury in rats[J]. Brain Res,2009,1297(11):177-184
[18]董军，闵苏，魏珂，等.异丙酚联合电休克治疗对抑郁大鼠海马和纹状体谷氨酸含量的影响[J].中华麻醉学杂志，2008，28(8)：704-707
[19]刘永峰，闵苏，董军，等.无抽搐电休克治疗大鼠抑郁症与海马-氨基丁酸通路的关系[J].中国神经精神疾病杂志，2009，35(4)：238-241
[20]董军，闵苏，魏珂，等.无抽搐电休克治疗大鼠抑郁症的谷氨酸能机制研究[J].中国神经精神疾病杂志，2008，35(5)：310-312
[21]刘媛媛，闵苏，董军，等.无抽搐电休克对抑郁大鼠学习记忆功能的影响及其突触可塑性机制[J].中国神经精神疾病杂志，2010，36(2)：70-74
[22] Osiecka KM, Nieznanska H, Skowronek KJ, et al. Tau inhibits tubulinoligomerization induced by prion protein[J]. Biochim Biophys Acta,2010,1813(10):1845-1853
[23] De Calignon A, Fox LM, Pitstick R, et al. Caspase activation precedes and leadsto tangles[J]. Nature,2010,464(16):1201-1204
[24]李芳序，卢静，许亚杰，等.老年性痴呆发病过程中内源性甲醛慢性损伤机制[J].生物化学与生物物理进展，2008，35(4)：393-400
[25] Combs B, Voss K, Gamblin TC, et al. Pseudohyperphosphorylation hasdifferential effects on polymerization and function of tau isoforms[J].Biochemistry,2011,50(44):9446-9456
[26] Canu N, Filesi I, PristeràA, et al. Altered intracellular distribution of PrPC andimpairment of proteasome activity in Tau overexpressing cortical neurons[J]. JAlzheimers Dis,2011,27(3):603-613
[27] Kopeikina KJ, Carlson GA, Pitstick R, et al. Tau accumulation causesmitochondrial distribution deficits in neurons in a mouse model of tauopathy andin human Alzheimer's disease brain[J]. Am J Pathol,2011,179(4):2071-2082
[28] Sun Q, Gamblin TC. Pseudohyperphosphorylation causing AD-like changes intau has significant effects on its polymerization[J]. Biochemistry,2009,48(25):6002-6011
[29]刘付宁，曹铭辉，梁建军，等.急性吗啡暴露对大鼠前额叶皮质Tau蛋白磷酸化及学习记忆的影响[J].临床麻醉学杂志，2010，26(1)：61-63
[30] Blazquez-Llorca L, Garcia-Marin V, Merino-Serrais P, et al. Abnormal Tauphosphorylation in the thorny excrescences of CA3hippocampal neurons inpatients with Alzheimer's disease[J]. J Alzheimers Dis,2011,26(4):683-698
[31] Bibow S, Ozenne V, Biernat J, et al. Structural impact of proline-directedpseudophosphorylation at AT8, AT100, and PHF1epitopes on441-residue Tau[J].J Am Chem Soc,2011,133(40):15842-15845
[32]李洁颖，晏勇，蔡志友，等.胰岛素信号通路磷脂酰肌醇-3激酶/丝氨酸苏氨酸蛋白激酶对海马神经元β-淀粉样前体蛋白裂解酶1表达的影响[J].中华神经科杂志，2009，42(11)：737-741
[33] Wu FY, Feng Q, Cheng M, et al. The activation of excitatory amino acidreceptors is involved in tau phosphorylation induced by cold water stress[J]. ProgBiochem Biophys,2010,37(5):510-516
[34] Kingston S, Mao LM, Yang L, et al. Propofol inhibits phosphorylation ofN-methyl-D-aspartate receptor NR1subunits in neurons[J]. Anesthesiology,2006,104(4):736-739
[35]于布为，薛庆生，夏梦，等.异丙酚对大鼠脑片不同性质损伤的影响[J].中华医学杂志，2003，83(13)：1176-1179
[36]戴泽平，田玉科，汪辉，等.全凭静脉麻醉老龄大鼠海马tau蛋白磷酸化水平与认知功能的关系[J].临床麻醉学杂志，2008，24(3)：230-232
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