发育期铅暴露对大鼠学习记忆功能的损伤及药物和行为的干预
|
摘要
慢性铅暴露可以引起学习记忆和认知功能的损伤,长时程增强(long-termpotentiation,LTP)被认为是与学习记忆相关的一种突触可塑性模型,被广泛应用于研究学习记忆的细胞机制。已有研究结果表明,在发育早期(孕期和哺乳期),慢性铅暴露损伤了大鼠空间学习记忆,同时损伤了海马CA1区和DG区的LTP的诱导。目前临床上治疗铅中毒的主要药物为鳌合剂,由于其并不能修复因铅引起的学习记忆损伤及其本身的副作用等弊端,鳌合剂不适合长期低铅暴露的儿章。因此,积极探索治疗效果明显且能有效修复其学习记忆损伤的药物和有关心理行为干预方法显得意义重大。有文献报道腺苷蛋氨酸(S -adenosyl-L-methionine,SAM)能降低铅中毒大鼠及病人血铅浓度及升高血δ-氨基乙酰丙酸脱水酶(δ-Aminolevulinic Acid Dehydratase,ALAD)活力,但其对铅暴露导致的学习记忆功能损伤有无作用国内外未见报道,由于该药对儿童尚未发现明显的毒副作用,因此对该药进行进一步的研究非常有实际意义。丰富的环境刺激这一低成本低风险的心理行为干预方法已被广泛用于如低出生体重、缺血缺氧性脑病等脑发育异常的干预,对于发育早期铅中毒的神经毒性方面的干预研究较少。本文运用Morris水迷宫作为大鼠空间学习记忆的测试工具,并用在位场电位记录的方法在发育早期(孕期和哺乳期)慢性铅暴露大鼠模型上分别研究了药物腺苷蛋氨酸和心理行为干预——丰富的环境刺激对发育早期慢性铅暴露造成的空间学习记忆和突触可塑性损伤的修复和保护作用,主要的研究方法和结果如下:
1.自母鼠受孕第1天至仔鼠断奶为止给予母鼠1.5g/L的醋酸铅饮用水染铅,对照组则饮用自来水,仔鼠断奶后选取雄性仔鼠每天腹腔注射20mg/kg的SAM或10ml/kg的生理盐水,为期22天,在44—54天时进行Morris水迷宫试验及在海马DG区记录兴奋性突触后电位(excitatory postsynaptic potential,EPSP)和群峰电位(population spike,PS),并检测血铅和血、脑、海马的氧化指标。结果表明:发育早期慢性铅暴露可以明显延长大鼠在水迷宫的逃避潜伏期、缩短在原平台象限的游泳时间,并且明显降低DG区诱导的EPSP和PS LTP幅度,而在铅+SAM组发现其对铅暴露引起的空间学习记忆损伤和海马LTP损伤有明显的改善作用。同时还发现给予SAM能降低铅组大鼠的血铅浓度,提高了肝脏、脑及海马组织中GSH含量,降低了肝脏、脑组织中MDA含量。结果提示SAM对临床上慢性铅中毒儿童,尤其对学习记忆功能损伤的修复可能具有一定意义。
2。自母鼠受孕第1天至仔鼠断奶为止给予母鼠1.5g/L的醋酸铅饮用水染铅,对照组则饮用自来水,21天断奶后停止喂铅,将两组仔鼠中的雄鼠用以接下来的实验:两组中各随机挑选一半为普通环境饲养,另一半在丰富的环境条件下饲养,直至实验结束,这样就将动物最终分成了四组:正常对照组(Con)、对照+丰富环境组(Con/EE)、铅组(Pb)、铅+丰富环境组(Pb/EE)。在大鼠出生后56天时对四组大鼠实施Morris水迷宫试验及在海马DG区记录兴奋性突触后电位(excitatory postsynaptic potential,BPSP)和群峰电位(population spike,PS),结果发现丰富的环境刺激能修复发育期铅暴露所致的空间学习记忆损伤和因铅暴露而受损的大鼠海马DG区的EPSP和PSLTP,与对照组相比差异无显著性。
Chronic developmental lead exposure is known to be associated with learningand memory and cognitive dysfunction in children. Synaptic plasticity such aslong-term potentiation (LTP) is believed to be the mechanism underling certain typeof learning and memory. The hippocampus-dependent spatial learning and memoryare correlated closely with hippocampal LTP, impairment of which often leads tomemory deficits. Previous studies have demonstrated that Pb impairs LTP of CA1 invitro and LTP of dentate gyrus in vivo. At present, chelation therapy is popular fortreating lead-induced neurotoxicity. But the common chelation agents have manyadverse effects and are incapable of alleviating lead-induceed neurotoxicity. It is veryimportant to explore medicine and intervention to rescue the impairment of learningand memory induced by lead. S-adenosyl-L-methionine (SAM) has beendemonstrated effective in reducing blood lead concentation and improving ALADactivity in humans and rats. But it is not clear if SAM is helpful to rescue theimpairment of learning and memory induced by lead. Enriched environment(EE) hasbeen adopted to interfere some brain damage such as very low birth weight andhypoxic-ischemic encephalopathy(HIE).Epidemiological studies showed that thechildren exposed to low lead from fortunate socioeconomic environments werecognitively intact while those in poor socioeconomic environments were cognitivelyimpaired. It is not very clear about the change of synaptic plasticity by EE treatmenton lead-exposed rats. In this thesis, the studies were carried out to investigate SAMand EE on the impairment of spatial learning and memory and LTP induced bydevelopmental lead exposure respectively. The results as follows:
1.Rats drank 1500ppm lead acetate (PbAc) solution or distilled water throughout gestation and lactation. After weaning at postnatal day 22, one half of the control and lead-exposed male offspring were intraperitoneally injected 20 mg SAM/kg daily over a period of 20-22 days. Electrophysiological and Morris Water maze (MWM) test were performed at 44-54 days of age. The blood lead concentration and oxidative stress in liver, brain and hippocampus were also detected in the four groups as well. The result showed that the impaired learning ability induced by lead could be improved significantly by SAM. Furthermore, our results revealed that EPSP LTP and PS LTP impairments induced by lead were also ameliorated by SAM treatment. A significant recovery of blood lead, liver, brain glutathion (GSH) and malondialdehyde (MDA) level was clearly produced in lead-exposed rats after SAM treatment as well. This study showed that SAM is beneficial in the treatment of lead intoxication especially in the rescue of learning and memory impairment induced by lead and deserves more detailed research.
2. Rats drank 1500ppm PbAc solution or distilled water throughout gestation and lactation. After weaning at postnatal day 21, one half of the control and lead-exposed male offspring were given the environmental enrichment treatment through all experiments until tested. Electrophysiological and Morris Water maze test were performed at 8 weeks of age. The result showed that the impaired learning ability induced by lead could be reversed by EE. Furthermore, our results revealed that EPSP LTP and PS LTP impairments induced by lead were also reversible by EE experience.
1.自母鼠受孕第1天至仔鼠断奶为止给予母鼠1.5g/L的醋酸铅饮用水染铅,对照组则饮用自来水,仔鼠断奶后选取雄性仔鼠每天腹腔注射20mg/kg的SAM或10ml/kg的生理盐水,为期22天,在44—54天时进行Morris水迷宫试验及在海马DG区记录兴奋性突触后电位(excitatory postsynaptic potential,EPSP)和群峰电位(population spike,PS),并检测血铅和血、脑、海马的氧化指标。结果表明:发育早期慢性铅暴露可以明显延长大鼠在水迷宫的逃避潜伏期、缩短在原平台象限的游泳时间,并且明显降低DG区诱导的EPSP和PS LTP幅度,而在铅+SAM组发现其对铅暴露引起的空间学习记忆损伤和海马LTP损伤有明显的改善作用。同时还发现给予SAM能降低铅组大鼠的血铅浓度,提高了肝脏、脑及海马组织中GSH含量,降低了肝脏、脑组织中MDA含量。结果提示SAM对临床上慢性铅中毒儿童,尤其对学习记忆功能损伤的修复可能具有一定意义。
2。自母鼠受孕第1天至仔鼠断奶为止给予母鼠1.5g/L的醋酸铅饮用水染铅,对照组则饮用自来水,21天断奶后停止喂铅,将两组仔鼠中的雄鼠用以接下来的实验:两组中各随机挑选一半为普通环境饲养,另一半在丰富的环境条件下饲养,直至实验结束,这样就将动物最终分成了四组:正常对照组(Con)、对照+丰富环境组(Con/EE)、铅组(Pb)、铅+丰富环境组(Pb/EE)。在大鼠出生后56天时对四组大鼠实施Morris水迷宫试验及在海马DG区记录兴奋性突触后电位(excitatory postsynaptic potential,BPSP)和群峰电位(population spike,PS),结果发现丰富的环境刺激能修复发育期铅暴露所致的空间学习记忆损伤和因铅暴露而受损的大鼠海马DG区的EPSP和PSLTP,与对照组相比差异无显著性。
Chronic developmental lead exposure is known to be associated with learningand memory and cognitive dysfunction in children. Synaptic plasticity such aslong-term potentiation (LTP) is believed to be the mechanism underling certain typeof learning and memory. The hippocampus-dependent spatial learning and memoryare correlated closely with hippocampal LTP, impairment of which often leads tomemory deficits. Previous studies have demonstrated that Pb impairs LTP of CA1 invitro and LTP of dentate gyrus in vivo. At present, chelation therapy is popular fortreating lead-induced neurotoxicity. But the common chelation agents have manyadverse effects and are incapable of alleviating lead-induceed neurotoxicity. It is veryimportant to explore medicine and intervention to rescue the impairment of learningand memory induced by lead. S-adenosyl-L-methionine (SAM) has beendemonstrated effective in reducing blood lead concentation and improving ALADactivity in humans and rats. But it is not clear if SAM is helpful to rescue theimpairment of learning and memory induced by lead. Enriched environment(EE) hasbeen adopted to interfere some brain damage such as very low birth weight andhypoxic-ischemic encephalopathy(HIE).Epidemiological studies showed that thechildren exposed to low lead from fortunate socioeconomic environments werecognitively intact while those in poor socioeconomic environments were cognitivelyimpaired. It is not very clear about the change of synaptic plasticity by EE treatmenton lead-exposed rats. In this thesis, the studies were carried out to investigate SAMand EE on the impairment of spatial learning and memory and LTP induced bydevelopmental lead exposure respectively. The results as follows:
1.Rats drank 1500ppm lead acetate (PbAc) solution or distilled water throughout gestation and lactation. After weaning at postnatal day 22, one half of the control and lead-exposed male offspring were intraperitoneally injected 20 mg SAM/kg daily over a period of 20-22 days. Electrophysiological and Morris Water maze (MWM) test were performed at 44-54 days of age. The blood lead concentration and oxidative stress in liver, brain and hippocampus were also detected in the four groups as well. The result showed that the impaired learning ability induced by lead could be improved significantly by SAM. Furthermore, our results revealed that EPSP LTP and PS LTP impairments induced by lead were also ameliorated by SAM treatment. A significant recovery of blood lead, liver, brain glutathion (GSH) and malondialdehyde (MDA) level was clearly produced in lead-exposed rats after SAM treatment as well. This study showed that SAM is beneficial in the treatment of lead intoxication especially in the rescue of learning and memory impairment induced by lead and deserves more detailed research.
2. Rats drank 1500ppm PbAc solution or distilled water throughout gestation and lactation. After weaning at postnatal day 21, one half of the control and lead-exposed male offspring were given the environmental enrichment treatment through all experiments until tested. Electrophysiological and Morris Water maze test were performed at 8 weeks of age. The result showed that the impaired learning ability induced by lead could be reversed by EE. Furthermore, our results revealed that EPSP LTP and PS LTP impairments induced by lead were also reversible by EE experience.
引文
1.刘梅,陆伦根,窦爱霞,等.2007.S-腺苷蛋氨酸对人肝星状细胞增殖和氧应激及转化生长因子β1表达的影响.肝脏12(2):99-102.
2.缪锟,孙亮,于莲珍等.1999.腺苷蛋氨酸治疗慢性酒精性肝病合并重度肝内胆汁瘀积的评估.江苏医药.25(12):940-942.
3.柯伟群.2002.新生儿病理性黄疽病因分析.中华中西医结合杂志,2(9):137-139.
4.刘永泉,樊晶光,1997.驱铅治疗辅助药物的研究进展.国外医学卫生学分册.24,10-11.
5.潘小萍.2006.腺苷蛋氨酸佐治新生儿高胆红素血症.儿科药学杂志.12(6):33-35.
6.沈晓明.1996.儿童铅中毒.北京:人民卫生出版社.
7.王慕邀.2000.儿科学.第5版.北京:人民卫生出版社 117-118.8.谢玲琳,朱长虹,田卫群.2003.L-蛋氨酸驱铅对小鼠体内微量元素的影响.中华劳动卫生职业病杂志.2:108-110.
9.颜崇淮,沈晓明.2006.儿童铅中毒处理中值得注意的问题.中国实用儿科杂志,21(3):171—173.
10.袁宝珊,吴宜群.1998.环境铅污染与儿童健康.国外医学卫生学分册,25:193-198.
11.张频,黄砚青,王雪芬,等.2007.腺苷蛋氨酸对酒精性肝损伤大鼠甲硫氨酸代谢和脂质过氧化的影响.临床肝胆病杂志.23(1):158-161.
12.Agricola R,Dalla Verde G,Urani R,et al.1994.S-adenosyl-L-methionine in the treatment of major depression complicating chronic alcoholism.Curr Ther Res.55:83-92.
13.Alvarez E,Udina C,Guillamat R.1987.Shortening of latency period in depressed patients treated with SAMe and other antidepressant drugs.Cell Biol Rev.S1:103-110.
13.Apte M.2002.Oxidative stress:Does it "initiate" hepatic stellate cell activation or only "perpetuate" the process? J Gastroenterol Hepatol,17:1045-1048.
14. Bell KM, Potkin SG, Carreon D ,et al. 1994.S-adenosylmethionine blood levels in major depression: changes with drug treatment. Acta Neurol Scand Suppl. 154:15—18.
15. Bottiglieri T, Godfrey P, Flynn T, et al. 1990. Cerebrospinal fluid S-adenosylmethionine in depression and dementia:effects of treatment with parenteral and oral S-adenosylmethionine.J Neurol Neurosurg Psychiatry .53:1096-1098.
16 . Bressa GM.1994.S-Adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies. Acta Neurol Scand. 154 (suppl):7-14.
17. Burns JM, Baghurst PA, Sawyer MG,et al. 1999.Lifetime low-level exposures to environmental lead and children' s emotional and behavioral development at ages 11～13 years.The Port Pirie Cohort Study. Am J Epidemiol. 149:740-749.
18. Catalino S, Scarponi S, Cesa F, et al. 1992. Efficacy and safety of intravenous S-Adenosyl-L -Methionine in the mangement of intrahepatic cholestasis of pregnancy. Drugs Invest, 4 (Supp 14): 78-82.
19. Cerutti R, Scichel MP, Perin M, et al. 1993. Psychological distress during puerperium: a novel therapeutic approach using S-adenosylmethionine. Curr Ther Res. 53:707-716.
20. Chawla RK, Lewis FW, Kutner M et al. 1984. Plasma cysteine, cystine, and glutathione in cirrhosis.Gastroenterology. 87, 770-776.
21. David M, Maurizio F. 2002.Role of S-adenosyl-L-methionine in the treatment of depression:a review of the evidence. Am J Chin Nutr. 76(5): 1158S-1161S.
22. Di Rocco A, Rogers JD, Brown R, et al. 2000.S-Adenosyl-methionine improves depression in patients with Parkinson's disease in an open-label clinical trial. Mov Disord. 15:1225-1229.
23. Flora GJ, Seth PK. 1999. Beneficial effects of S-adenosyl-L-methionine on aminolevulinic acid dehydrase,glutathione and lipid peroxidation during acute lead-ethanol administration in mice. Alcohol. 18(2—3): 103—108.
24 . Fontanari D, DiPalma C, Giorgetti G, et al. 1994.Effects of S-adenosyl-L-methionine on cognitive and vigilance functions in elderly. CurrTher Res.55:682-689.
25. Frezza M, Pozzato G , Chiesa L. 1984. Reversal of intrahepatic cholestasis ofpregnancy in women after high dose S2adenosyl2L2methionine administration. Hepatology. 4 (2): 274-278.
26. Hill DB,Deaciuc IV, Nanji AA et al. 1998.Mechanisms of hepatic injury in alcoholic liver disease.Clin Liver Dis. 2: 703-721.
27. Horowitz JH, Rypins EB, Henderson JM et al. 1981. Evidence for impairment of transsulfuration pathway in cirrhosis.Gastroenterology. 81, 668-675.
28. Jiang W, Yang CQ, LiuWB, et al. 2004.Blockage of transforming growth factor β recep tors prevents progression of ig serum- induced rat liver fibrosis. World J Gastroenterol, 10(11) : 1634-1638.
29. Kufferle B, Grunberger J. 1982.Early clinical double-blind study with S-adenosyl-L-methionine: a new potential antidepressant. In: Costa E, Racagni G, eds. Typical and atypical antidepressants. New York: Raven Press. 175-180.
30. Lo Russo A, Monaco M, Pani A, et al. 1994. Efficacy of S-adenosyl methionine in relieving psychologic distress associated with detoxification on opiate abusers. Curr Ther Res. 55:905-913.
31 . Manzillo G, Piccinino F, Surrenti C. 1992. Multicenter. double-blind, placebo-controlled study of intravenous and oral S-adenosyl-L-methionine in cholestatic patients with liver disease. Drug Invest. 4 (supp 14):90-100.
32. McClain CJ, Barve S, Deaciuc I et al. 1999.Cytokines in alcoholic liver disease. Semin Liver Dis 19,205-219.
33. McClain C, Barve S, Joahi-Barve S, et al. 2005. Dysregulated cytokine metabolism, altered hepatic methionine metabolism and proteasome dysfunction in alcoholic liver disease. Alcohol Clin Exp Res, 29(11 Suppl):180S-188S
34. McClain CJ, Hill DB,Song Z,et al. 2002. S-Adenosylmethionin, cytokines, and alcoholic liver disease. Alcohol, 27(3): 185-192.
35. Miccoli L, Porro V, Bertolino A. 1978.Comparison between the antidepressant activity of S-adenosyl-L-methionine (SAMe) and that of some tricyclic drugs. Acta Neurol (Napoli).33:243-255.
36. Morrison LD,Smith DD,Kish SJ. 1996.Brain S-adenosylmethionine levels are severely decreased in Alzheimer's disease. J Neurochem. 67(3): 1328-1331.
37. Munoz JJ,Roca C,Santos JL,et al. 1993. Effect of zinc or S-adenosyl-L-methionine on long term administration of low doses of lead to rats.Pharmacol Toxicol, 73:189—191.
38. Nieto N, Cederbaum AI. 2005.S-adenosylmethionine blocks collagen I production by p reventing TGF beta induction of the COL1A2 promoter. Biol Chem, 280(35) : 30963-309674.
39. Nieto N, Friedman SL, Cederbaum AI. 2002. Cytochrome P450 2E12derived oxygen species mediate paracrine stimulation of collagen I protein synthesis by hepatic stellate cells. J Biol Chem, 277 : 9853-9864
40. Parades SR, Kozicki PA, Batlle AM. 1987.S-adenosyl-L-methionine a counter to lead intoxication? Comp Biochem Physiol B, 1985,82(4): 751 -757.
41. Rodncy LL, Barham SB, Jackob M. 1999.Methionine residues may protect proteins from critical oxidative damage. Mech Ageing Dev. 107;323-332
42. Sougioultzis S, Dalakas E,Hayes PC,et al. 2005. Alcoholic hepatitis:from pathogenesis to treatment. Curr Med Res Opin, 21 (9): 1337-1346.
43 . Spillmann M, Fava M. 1996. S-adenosyl-methionine (ademethionine) in psychiatric disorders. CNS Drugs.6:416-425.
44. Svegliati BG, Ambrosio L, Ferretti G, et al. 1998.Fibrogenic effect of oxidative stress on rat hepatic stellate cells. Hepatology.27: 720-726.
45. Tsai SM, Lee KT, Tsai LY. 2001. Effects of S2adenosyl2L2methionine on liver damage in experimental obstructive jaundice. Kaohsiung J Med Sci ,17 : 455-460.
46. Wang X, Cederbaum AI. 2006.S — adenosyl — L — methionine attenuates hepatotoxicity induced by agonistic Jo2 Fas antibody following CYP2E1 induction in mice. J Pharmacol Exp Ther.317: 44252.
47. Wu D , Cederbaum AI. 2006.Opposite action of S2adenosyl methionine and its metabolites on CYP2E12mediated toxicity in pyrazole2induced rat hepatocytes and HepG2 E47 cells. AmJ Physiol Gastrointest Liver Physiol ,290 : 674-684.
48.Xie L,Gao Q,Xu H.2003.Ameliorative effect of L-methionine on Pb-exposed mice.Biol Trace Elem Res.93(1-3):227-236.
49.Yatsuqi S,Yamamoto T,Ohno.M,et al.1989.Effect of S-adenosyl-L-methionine on impairment of working memory induced in rats by cerebral ischemia and scopolamine.Eur J Pharmacol.166(2):231-239.
1.安继业,姚梅玲,冯彩英等.2007.早期教育对婴幼儿神经心理发育影响的探讨.医药论坛杂志.28(2):16—19
2.鲍秀兰.10～3岁儿童教育的重要性.实用儿科临床杂志.2003,(4):243
3.曹云,邵肖海等,2000.环境刺激对缺氧缺血性脑损伤鼠突触结构的影响,中国生育健康杂志.11(3):104—106.
4.郭建华,满立新,甘晓虹等2007.驱铅合并感觉统合训练治疗感觉统合失调儿童的临床疗效.中国行为医学科学.16(1):35—38.
5.胡君,林秋君,陈燕惠.等.2004.早期干预对脑损伤大鼠学习记忆及神经生长因子的影响.中国心理卫生杂志.18(7):491—494.
6.李亚,吴馥梅.1999.突触后致密结构的一些研究进展.神经解剖学杂志.15(3):293-295.
7.李雪梅,蒲昭霞,周晓军.2008.环境刺激对缺氧缺血性脑损伤新生大鼠海马微管相关蛋白-2表达的影响,中国新生儿科杂志.23(1):15-18
8.李松,洪世欣,王大海,等.2003.早产儿和低体重及小于胎龄儿与脑瘫发生的关系.中华儿科杂志.41:344-347.
9.鲁利群,赵聪敏,蒲昭霞.2006.环境刺激对缺氧缺血性脑损伤大鼠海马巢蛋白表达及学习记忆的影响.第三军医大学学报.28(8):804-806.
10.潘嘉敏.2004.幼儿血铅水平与环境因素的相关性研究.中国妇幼保健.19(16):32—34.
11.施莉萍.2002.如何促进儿童智力发展.现代特殊教育.6:6—7.
12.沈晓明.2006.儿童脑科学研究的临床和教育意义:研究到应用.中国儿童保健杂志.14(1):1.
13.吴馥梅,杜红燕,章子贵.等.1994.突触界面曲率及其生理意义.神经解剖 杂志,10(1):89-92.
14.徐海青,张晓蓉,陈自励.1999.环境因素对早产低体重儿智能发育的影响.中国儿童保健杂志.7(4):235—237.
15.杨玉华.2005.家庭环境对儿童全血铅的影响.微量元素与健康研究.22(1):36—39.
16.Adembri C,Venturi L,Tani A,et al.2006.Neuroprotective effects of propofol in models of cerebral ischemia:inhibition of mitochondrial swelling as a possible mechanism.Anesthesiology.104(1):80-89.
17.Alkondon M.,Costa AC,Radhakrishnan V et al.1990.Selective blockade of
NMDA-activated channel currents may be implicated in learning deficits caused by
lead.FEBS Lett.261,124-130.
18.Aunt JV,Gooper BAB,Today WA.1988.Very low—brith—weight infant at 8and 11 years of age:role of neonatal illness and family status.Pediatrics.82:596-561.
19.Bai G.,Kusiak JW.1995.Functional analysis of the proximal 5-flanking region of the N-methyl-D-aspartate receptor,subunit gene,NMDAR1.J Biol Chem.270:7737-7744.
20.Bai G.,Kusiak JW.1997.Nerve growth factor up-regulate the N-methyl-D-aspartate receptor subunit 1 promotor,in PC12 cells.J Biol Chem.272:5936-5942.
21.Bellinger DC.2000.Effect modification in epidemiologic studies of low-level neurotoxicant exposures and health outcomes.Neurotoxicol.Teratol.22:133-140.
22.Bellinger DC,Leviton A,Waternaux C.et al.1988.Low-level lead exposure,social class,and infant development.Neurotoxicol.Teratol.10:497-503.
23.Bennett JC,McRae PA,Levy LJ et al.2006.Long-term continuous,but not daily,environmental enrichment reduces spatial memory decline in aged male mice.Neurobiol Learn Mem.85(2):139-152.
24.Bleecker ML,Lindgren KN,Ford DP,et al.2002.The interaction of education and cumulative lead exlposue on the Mini-Mental State Examination.J Occup Environ Med.44(6):574-578.
25 . Bona E, Johansson BB, Hagberg H. 1997.Sensorimotor function and neuropathology five or six weeks after hypoxic-ischemia in seven-day-old rats. Pediatr Res. 42: 678-683.
26. Bruno W, Rodrigur G, Christian K, et al. 2004. Recovery from brain injury in animals:relative efficacy of environmental enrichment, physical exercise or formal training(1990-1992).Progress in Neurobiol. 72:167-82.
27. Buchhold B, Mogoanta L, Suofu Y et al. 2007.Environmental enrichment improves functional and neuropathological indices following stroke in young and aged rats.Restor Neurol Neurosci. 25(5-6):467-84o
28. Cui MH, Yang Y, Yang JL et al. Enriched environment experience overcomes the memory deficits and depressive-like behavior induced by early life stress, Neuroscience Letters.2006,404: 208-212.
29. Day JC, Koehl M., Deroche V et al. 1998. Prenatal stress enhances stress- and corticotropin-releasing factor-induced stimulation of hippocampal acetylcholine release in adult rats, Journal of Neuroscience. 18:1886-1892.
30. Duffy SN, Craddock KJ, Abel T et al. 2001. Environmental enrichment modifies the PKA-dependence of hippocampal LTP and improves hippocampus-dependent memory. Learning & Memory. 8: 26-34.
31. Falkenberg T, Mohammed AK, Henriksson B. 1992. Increased expression of brain-derived neurotrophic factor mRNA in rat hippocampus is associated with improved spatial learning and enriched environment. Neuroscience Lett. 138:153-156.
32. Flahelty EG. 1995. Risk of lead poisoning in abused and neglected children.Clin Pediat. 34:128-132.
33. Guilarte, TR, Toscano CD, McGlothan JL et al. 2003. Environmental enrichment neurotrophic factor reverses cognitive and molecular deficits induced by developmental lead exposure. Ann Neurol. 53, 50-56.
34. Gobbo OL, O' Mara SM. 2004.Impact of enriched-environment housing on brain-derived and on cognitive performance after a transientglobal ischemia.Behav Brain Res. 152:231-241.
35. Hanas JS, Rodgers JS, Bantle JA.et al. 1999.Lead inhibition of DNA-binding mechanism of Cys (2) His (2) Zinc finger proteins.Mol Pharmacol. 56:982-988.
36 . Harburger LL, Lambert TJ,Firck KM 2007. Age-dependent effects of environmental enrichment on spatial reference memory in male mice. Behav Brain Res. 185(1):43-48.
37. Kawasaki T, Nishio T, Kawaguchi S, et al. 2001. Spatiotemporal distribution of GAP-43 in the developing rat spinal cord: a histological and quantitative immunofluorescence study. Neurosci Res. 39(3):347-358.
38. Koenig JI., Elmer G.I., Shepard PD et al. 2005.Prenatal exposure to a repeated variable stress paradigm elicits behavioral and neuroendocrinological changes in the adult offspring: potential relevance to schizophrenia. Behavioural Brain Research. 156:251-261.
39. Hayashi A, Nagaoka M, Yamada K et al. 1998.Maternal stress induces synaptic loss and developmental disabilities of offspring. International Journal of Developmental Neuroscience. 16:209-216.
40. Huang EJ, Reichardt LF 2001. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 24: 677-736
41. Kinnunen AK., Koenig JI. and G. Bilbe. 2003. Repeated variable prenatal stress alters pre- and postsynaptic gene expression in the rat frontal pole. Journal of Neurochemistry. 86: 736-748.
42. Koo JW, Park CH, Choi SH.et al. 2003.The postnatal environment can counteract prenatal effects on cognitive ability, cell proliferation, and synaptic protein expression, The FASEB Journal. 17:1556-1558.
43 . Kwon BK, Tetzlaff W. 2001. Spinal cord regeneration; from gene to transplants.Spine. 26(24 Suppl): 13-22.
44. Jodi E. Gresac K, Kristin M. et al. 2007.Life-long environmental enrichment differentially affects the mnemonic response to estrogen in young, middle-aged, and aged female mice.Neurobiol Learn Mem. 88(4):393-408.
45. Lauren L. Harburger, Talley J.et al. 2007.Age-dependent effects of environmental enrichment on spatial reference memory in male mice.Behav Brain Res. 185(1):43-48.
46. Leggio MG, Mandolesi L, Federico F et al. 2005. Environmental enrichment promotes improved spatial abilities and enhanced dendritic growth in the rat. Behavioural Brain Research. 163:78-90.
47. Lemaire V, Lamarque S, Moal ML et al. 2006. Postnatal stimulation of the pups counteracts prenatal stress-induced deficits in hippocampal neurogenesis. Biological Psychiatry. 59:786-792.
48. Liu A,Prenger MS, Norton DD. 2001. Nerve growth factor uses Ras/ERK and phosphatidylinositol 3-kinase cascades to up-regulate the N-methyl-D-aspartate receptor 1 promotor. J Biol Chem. 276:45372-45379.
49. Lordi B. Lordi, Patin V., Protais P.et al. 2000. Chronic stress in pregnant rats: effects on growth rate, anxiety and memory capabilities of the offspring, International Journal of Psychophysiology 37:195-205.
50. Maccari S., Darnaudery M., Morley-Fletcher S et al. 2003. Prenatal stress and long-term consequences: implications of glucocorticoid hormones, Neuroscience and Biobehavioral Reviews. 27:119-127.
51. Mayer SJ. 2005.The early evolution of Jean Piaget 's clinical method. Hist Psychol. 8 (4): 362-382
52. Markus EJ, Petit TL. 1989.Synaptic structural plasticity: role of synaptic shape.3(1):1-11.
53. Melman ST, Nimeh JW,Anbar RD. 1998.Prevalence of elevated blood lead levels in an inner citty pediatric popunation .Environment health perspect. 106:655-657.
54. Morley-Fletcher S, Rea M, Maccari S et al.. 2003. Environmental enrichment during adolescence reverses the effects of prenatal stress on play behaviour and HPA axis reactivity in rats. The European Journal of Neuroscience. 18: 3367-3374.
55. Murakami Y, Furukawa S, Nitta A, et al. 2002. Accumulation of nerve growth factor protein at both rostral and caudal stumps in the transected rat spinal cord.Neurol Sci, 198 (1-2): 63-69.
56. Nihei MK, Desmond NL, McGlothan JL et al. 2000.NMDA receptor subunit changes are associated with Pb~(2+) -induced deficits of LTP and spatial learning. Neuroscienc. 99:233-242.
57. Pascura R, Ftgueroa H. 1996.Effects of preweaning sensornigotor stimulation on behavioral and neuronal development in motor and visual of the rat1 Biol Neonate, 69: 399
58. Rampon C, Jiang CH, Dong H et al. 2000.Effects of environmental enrichment on gene expression in the brain, Proceedings of the National Academy of Sciences of the United States of America. 97:12880-12884.
59. Robinson S, Petelenz K, Li Q, et al.2005.Developmental changes induced by graded prenatal systemic hypoxic-ischemic insults in rats. Neurobiol Dis. 18(3): 568-581.
60. Rzmey CT, Ramey SL. 1998.Prevention of intellectual disabilties: early interventions of imp rove cognitive development 1PrevMed, 27 (2) :224-229
61. Schneider J.S, Lee MH., Anderson DW et al. 2001 .Enriched environment during development is protective against lead-induced neurotoxicity. Brain Research. 896:48-55.
62. Segvoia G,Del Arco A, Garrido P,et al. 2008.Environmental enrichment reduces the response to stress of the cholinergic system in the prefrontal cortex during aiging.Neurochem Int. 52(6): 1198-203.
63. van Praag H,Kempermann G, Gage FH. 2000.Neural consequences of environmental enrichment. Nat Rev Neurosce. 1:191-198.
64. Wolf SA,Kronenberg G, Lehmann K.et al. 2006.Cognitive and physical activity differently modulate disease progression in the amyloid precursor protein (APP)-23 model of Alzheimer's disease.Biol Psychiatry. 60(12):1314-1323.
65 . Wadhwa PD. 2005.Psychoneuroendocrine processes in human pregnancy influence fetal development and health. Psychoneuroendocrinology . 30: 724-743.
66. Weinstock M. 2001 .Alterations induced by gestational stress in brain morphology and behaviour of the offspring. Progress in Neurobiology. 65: 427-451.
67. Weinstock M., Poltyrev T., Schorer-Apelbaum D.et al. 1998.Effect of prenatal stress on plasma corticosterone and catecholamines in response to footshock in rats, Physiology & Behavior. 64: 439-444.
68. Yamauchi T. 2002. Molecular constituents and phosphorylation-dependent regulation of the postsynaptic density .Mass Spectrom Rev., 21 (4):266-286.
69. Yang JL, Han HL, Cao J et al. 2006.Prenatal stress modifies hippocampal synaptic plasticity and spatial learning in young rat offspring. Hippocampus. 16:431-436.
70. Yang J, Hou C, Ma N et al. 2007.Enriched environment treatment restores impaired hippocampal synaptic plasticity and cognitive deficits induced by prenatal chronic stress.Neurobiology of Learning and Memory. 87:257-264.
71.."Zawia NH, Sharan R, Brydie M. 1998. Spl as a target for metal-induced perturbations of transcriptional regulation of developmental brain gene expression. Dev Brain Res. 107:291-298.
72. Zhang XY, Liu AP, Ruan DY. et al. 2002.Effect of developmental lead exposure on the expression of specific NMDA receptor subunit mRNA in the hippocampus of neonatal rats by digoxigenin-labeled in situ hybridization histochemistry. Neurotoxicol Teratol. 24:149-160.
1.胡前胜,董胜章,任铁铃等.1999.儿童齿铅于智商知系的流行病学研究.环境与健康杂志.16(1):16—19.
2.李勇辉.2001.低浓度血铅对儿童神经心理的影响.湖南师范大学社会科学学报.30(S2):340-342.
3.李沛,董胜璋.1996.环境铅接触对儿童智力与行为影响的调查.环境与健康杂志.13(4):158-160.
4.秦锐,刘昔荣,周鸣等.2004.孕期铅暴露不同示标的意义及与婴儿神经行为发育.中国儿童保健杂志,12(2):99-102.
5.苏丽,吴清,李凤芝.2003.孕母中期血铅水平对妊娠结局影响的初探.广东微量元素科学.10(12):28—30.
6.沈晓明,颜崇淮.1996.低水平铅暴露对早期婴儿发育的影响1中华儿科杂志.34(4):255—257.
7.沈晓明 主编.1996.儿童铅中毒[M].北京:人民卫生出版社,:100-101
8.沈彤,朱中平,俞翠莲等.2006.铅暴露对婴幼儿发育商数影响的队列研究,22(8):906—908.
9.王郁文,程舜华;宋秀珍等.1996.铅暴露与儿童行为异常.中华预防医学杂志.30(3):147—152.
10.颜崇淮,沈晓明,敖黎明等.1997.上海市新生儿脐血铅水平及其影响因素.中华预防医学志.31(1):9-12.
11.俞苏蒙,王振刚,陈美娟等.1995.铅污染地区学龄儿童血铅水平与智商及神经行为功能关系的研究.环境与健康杂志.12(4):158-161.
12.张敬旭,符绍莲,胡江等.1997.脐血铅含量与新生儿神经行为发育的关系.中华预防医学杂志.31(4):215-217.
13.Belling D,Leviton A1987.Longitudinai analgses of prenatal lead exposure and postnatal lead exposure and early connitive development.N Eng L J Med.316:1037
14. Bellinger DC, Stilfs KM, Needleman HL, 1992.Low-level lead exposure, intelligence and academic achievement: a long-term follow-up study. Pediatrics, 90:855-861.
15. Busselberg D, Platt B, Michael D,et al. 1994. Mammalian voltage-activated calcium channel currents are blocked by Pb~(++),Zn~(++),and Al~(3+). J Neurophysiol 71: 234-245.
16. Canfield RL, Henderson CR, Cory - Slechta DA, et al. 2003. Intellectual impairment in children with blood lead concentrations below 10 μg per eciliter. N Engl J Med. 17(16): 1517-1526.
17. Environmental Protection Agency, 1986. Air Quality Criteria for Lead, Office of Health and Environmental Assessment. Research Trangle Park. NC.
18. Finkelstein Y, Sternfeld M, Flechter S. 1990. Septal dopaminergic-chilinergic interactions during stress. Stress Med. 6:3-7.
19 . Finkelstein Y, Markowitz ME, Rosen JF. 1998.Low-level lead-induced neurotoxicity in children: an update on central nevous system effects(Review). Brain Res Rev, 168-176.
20. Gardella C. 2001. Lead exposure in pregnancy:a review of the literature and argument for routine prenatal screening. Obstet. Gynecol. Surv. 56(4):231-238.
21. Ge SY, Ruan DY, Yu K, et al. 2001.Effects of Fe~(2+) on ion channels:Na~+ channel, delayed rectified and transient outward K~+ channels. Food Chem Toxicol. 39:1271-1278.
22. Gomaa A, Hu H, Bellinger D. et al. 2002.Maternal bone lead as anlindependent risk factor for fetal neurotoxicity: A p rospectivestudy. Pediatrics. 110: 110-118.
23. Guilarte TR, RC Miceli. 1992.Age-dependent effects of lead on [3H]MK-801 binding to the NMDA receptor-gated ionophore: in vitro and in vivo studies. Neurosci Lett. 148:27-30.
24. Hansen O, Trillngsgaard A, Beese I et al. 1987.Neuropsychological study of children with elevated dentine lead level. In Lindberg S, Hutchinson T(Eds.) Proceedings of the 6th International Conference on Heavy Metals in the Environment, CEP Consultants. Edinburgh 54-57.
25. Herschkowitz N, 1988. Brain development in the fetus, neonate and infant. Biol Neonate. 54:1-19.
26. Hunter J,Urbanowicz MA, Yule W,et al. 1985. Automated testing of reaction time and its assiciation with lead in children. Int. Arch. Occup. Enviro. Health. 57:27-34.
27. Ishihara K, Alkondon M, Montes JG et al. 1995. Ontogenically related properties of N-methyl-D-aspartate receptors in rat hippocampal neuros and the age-specific sensitivity of developing neurons to lead. J Pharmacol Exp Ther. 273:1459-1470.
28. Jett DA, Kuhlmann AC, Guilarte TR. 1997. Intrahippocampal administration of lead (Pb) impairs performance of rats in the Morris water maze. Pharmacol Biochem Behav.57(1-2):263-269.
29. Jett DA, Kuhlmann AC, Farmer SJ et al. 1997. Age-dependent effects of developmental lead exposure on performance in the Morris water maze. Pharmacol Biochem Behav . 57(1-2):271-279.
30. Kuhlmann, AC, McGlothan, JL, Guilarte, TR. 1997.Developmental lead exposure causes spatial learning deficits in adult rat. Neurosci Lett. 233:101-104.
31. Lasley SM. 1992. Regulation of dopaminergic activity, but not tyrosine hydroxylase, is diminished after chronic inorganiclead exposure. NeuroToxicology. 13:625-636.
32. LeMoal M, Simon H. 1991.Mesocorticolimbic dopaminergic network: functional and regulatory roles. Physiol.Rev. 17:155-234.
33. Mayfield S. 1983. Language and speech behaviors of children with undue lead absorption: a review of the literature. J Speech Hear Res. 26:362-378.
34. Minnema DJ. 1988.Calcium influx and neurotransmitter release from rat hippocampal synaptosomes exposed to lead. Toxicol App Pharmacol.92,351-357.
35. Needleman HL. 1992. Effects of low levels of lead exposure. Science. 256:294-295.
36. Needleman HL, Landrigan PJ. 2004. What level of lead in blood is toxic for a child. Am J Public Health. 94: 8-9.
37. Otto DA, Fox DA. 1993.Auditory and visual dysfunction following lead exposure. Neurotoxicology.14:191-208.
38. Patel AB,MamtaniMR, Thakre TP et al. 2006. Association of umbilicalcord blood lead with neonatal behavior at varying levels of exposure. Behav Brain Funct. 2:22-28.
39. Pirkle JL. 1994.The decline in blood lead levels in the United StateslJAMA. 272: 284
40. Pocock SJ, Smith M, Baghurst P. 1994. Encironmental lead and children's entelligence:a systematic review of ht epidemiological evidence. BMJ. 309:1189-1197.
41. Schwartz J. 1993 .Beyond LOEL's p-values and vote counting: methods for looking at the shapes and strength of associations. Neurotoxicology . 14:237-248.
42. Schwartz J , Otto DA. 1987.Blood lead, hearing thresholds and neurobehavioral development in children and youth. Arch Environ.Health 42:153-160.
43 . Schwartz J,Otto DA. 1991. Lead and minor hearing impairment. Arch. Environ.Health 46:300-305.
44. Richard L, Canfield Ph.D. 2003.Intellectual impairment in children with blood lead concentrations below 10 μg/dl.The New England Journal of Medicine. 348(16): 1517-1523
4.5. Rosen JF.1992.Effects of low levels of lead exposure. Science. 256(1):294—299.
46. Ruan DY,Chen JT,Zhao C, et al.1998.Impairment of long-term potentiation and paired-pulse facilitation in rat hippocampal dentate gyms following developmental lead exposure in vivo. Brain Res. 806:196-201.
47. Schanne FA, Long GL, Rosen JF. 1997.Lead induced rise in intracellular free calcium in mediated through protein kinase C in osteoblastic bone cells. Biochem BiophysActa 1360:247-254.
48. Shen XM, Rosen JF, Guo D, et al. 1996. Childhood lead poisoning in China. Sci Total Enviro. 181:101-109.
49. Shellenberger M, 1998.Effects of early lead exposure on neurotransmitter systems in the brain: a review with commentary. Neurotoxicol 45,117-122.
50 . Sibergeld EK, Goldberg AM, 1975. Pharmacological and neurochemical
investigations of lead induced hyperactivity.. Neuropharmacology . 14:434-444.
51. Smith M. 1989.The effects of low- level lead exposure on children In:Smith MA, Grant LD.Eds.Lead Exposure and Child Development: An Internation Assessment.Dordrecht: Kluwer Academic Publishers:3-47
52. Sui L,Ge SY, Ruan DY, et al. 2000. Age-related impairment of long-term depression in area CA1 and dentate gyrus of rat hippocampus following developmental lead exposure in vitro. Neurotoxicol Teratol. 22:381-387.
53. Ujihara H, Sasa M, Ban T. 1995.Selective blockade of P-type calcium channels by lead in cultured hippocampal neurons. Jpn J Pharmacol. 67:267-269.
54. Winneke G, Beginn U, Ewert T,et al. 1985. Comparing the effects of perinatal and later childhood lead exposure on neuropsychological outcome. Environ. Res. 38:155-167.
55. Xu YZ, Ruan DY, Wu Y, et al. 1998.Nitric oxide affects LTP in area CA1 and CA3 of hippocampus in low-level lead-exposed rat.Neurotoxicol Teratol. 20:69-73.
56. Yang Y,Ma Y,Ni L et al. 2003. Lead exposure through gestation-only caused long-term learning/memory deficits in young adult offspring.Experimental Neurology. 184:489-495.
57. Zhao WF,Ruan DY, Xu YZ, et al. 1999. The effects of chronic lead exposure on long-term depression in area CA1 and dentate gyrus of rat hippocampus in vitro. Brain Res. 818:153-159.
[1] Khan, N.Z., & Khan,A.H. (1999).Lead poisoning and psychomotor delay in Bangladeshi children. Lancet, 353, 754.
[2] Mushak, P., Davis, J.M., Crocetti, A.F., Grant, L.D. (1989). Prenatal and postnatal effects of low-level lead exposure: integrated summary of a report to the US Congress on childhood lead poisoning. Environ Res, 50, 11-36.
[3] Winneke, G, Lilienthal, H., Kramer, U. (1996). The neurobehavioural toxicology and teratology of lead, Arch.Toxicol. 18(Suppl.),57-70
[4] Yang, Y, Ma, Y, Ni, L., Zhao, S., Li, L, Zhang, J, Fan, M., Liang, C, Cao, J., Xu, L.(2003).Lead exposure through gestation-only caused long-term learning/memory deficits in young adult offspring, Experimental Neurology, 184, 489-495.
[5] Kuhlmann, A.C, McGlothan, J.L., Guilarte, T.R. (1997). Developmental lead exposure causes spatial learning deficits in adult rat. Neurosci Lett, 233,101-104.
[6] Alfano, D.P., Petit,T.L.(1982).Neonatal lead exposue alters the dendritic development of hippocampal dentate granule cells. Exp. Neurol,75,275-288
[7] Petit, T.L., Alfano, D.P., LeBoutillier J.C.(1983).Early lead exposure and the hippocampus :a review and recent advance, Neurotoxicology, 4,79-94
[8] Bellinger,D.C. (2000). Effect modification in epidemiology studies of low-level neurotoxicant exposure and health outcomes, Neurotoxicol.Teratol.22,133-140
[9] Bellinger,D.C, Leviton, A., Waternaux ,C.,Needleman ,H., Rabinowitz M.M.(1988). Low-level lead exposure , social class, and infant development. Neurotoxicol.Teratol 10,497-503
[10] Fox, C, Merali,Z., Harrison, C.(2006).Therapeutic and protective effect of environmental enrichment against psychogenic and neurogenic stress. Behav.Brain Res,175,l-8
[11]Schneider, J.S., Lee, M.H., Anderson, D.W., Zuck, L., Lidsky, T. I. (2001). Enriched environment during development is protective against lead-induced neurotoxicity. Brain Research, 896, 48-55.
[12]Guilarte, T.R., Toscano, C.D., McGlothan, J. L, Weaver, S.A. (2003). Environmental enrichment reverses cognitive and molecular deficits induced by developmental lead exposure. Ann Neurol,53, 50-56.
[13] Bliss, T. V., & Collingridge, G. L. (1993). A synaptic model of memory:long-term potentiation in the hippocampus. Nature, 361,31 -39.
[14] Ruan, D.Y., Chen, J.T., Zhao, C, Xu,Y.Z., Wang, M., Zhao,W.F. (1998). Impairment of long-term potentiation and paired-pulse facilitation in rat hippocampal dentate gyrus following developmental lead exposure in vivo. Brain Res, 806,196-201.
[15] She, J.Q, Wang, M., Zhu, D.M., Sun, L.G., Ruan,D.Y. (2005). Effect of ganglioside on synaptic plasticity of hippocampus in lead-exposed rats in vivo. Brain. Research, 1060,162-169.
[16] Zhu, D.M., Wang, M., She, J.Q., Yu, K., Ruan, D.Y. (2005). Protection by a taurine supplemented diet from lead-induced deficits of long-term potentiation/depotentiation in dentate gyrus of rats in vivo. Neuroscience,134, 215-224.
[17] Alkondon, M., Costa, A.C., Radhakrishnan, V., Aronstam, R.S., Albuquerque, E.X. (1990). Selective blockade of NMDA-activated channel currents may be implicated in learning deficits caused by lead. FEBS Lett, 261,124-130.
[18] Guilarte,T.R., & Miceli,R.C. (1992). Age-dependent effects of lead on [~3H] MK-801 binding to the NMDA receptor-gated ionophore: in vitro and in vivo studies. Neurosci Letters, 148,27-30.
[19] Nihei, M.K., Desmond, N.L., McGlothan, J.L. Kuhlmann A.C, Guilarte T.R. (2000). NMDA receptor subunit changes are associated with Pb~(2+) -induced deficits of LTP and spatial learning. Neuroscienc, 99,233-242.
[20] Zhang, X.Y., Liu,A.P., Ruan, D.Y, Liu, J. (2002). Effect of developmental lead exposure on the expression of specific NMDA receptor subunit mRNA in the hippocampus of neonatal rats by digoxigenin-labeled in situ hybridization histochemistry. Neurotoxicol Teratol, 24,149-160.
[21]Bai, G.,Kusiak J.W.(1995).Functional analysis of the proximal 5-flanking region of the N-methyl-D-aspartate receptor subunit gene, NMDAR1. J Biol Chem.270,7737-7744.
[22] Hanas,.J.S.,Rodgers, J.S, Bantle, J.A.,Cheng ,Y.G.(1999). Lead inhibition of DNA-binding mechanism of Cys2His2 Zinc finger proteins.Mol Pharmacol.56,982-988.
[23]Zawia N.H., Sharan R., Brydie M.(1998). Sp1 as a target for metal-induced perturbations of transcriptional regulation of developmental brain gene expression. Dev Brain Res. 107,291-298.
[24] van Praag H., Kempermann G, Gage F.H.(2000). Neural consequences of environmental enrichment. Nat Rev Neurosce. 1,191-198.
[25]Falkenberg T., Mohammed A.K., Henriksson B.(1992). Increased expression of brain-derived neurotrophic factor mRNA in rat hippocampus is associated with improved spatial learning and enriched environment. Neuroscience Lett 138,153-156.
[26]Bai G, Kusiak J.W.(1997).Nerve growth factor up-regulate the N-methyl-D-aspartate receptor subunit 1 promotor in PC12 cells. J Biol Chem.272,5936-5942.
[27] Liu A.,Prenger M.S., Norton DD.(2001). Nerve growth factor uses Ras/ERK and phosphatidylinositol 3-kinase cascades to up-regulate the N-methyl-D-aspartate receptor 1 promotor. J Biol Chem. 276,45372-45379.
[28]Korte, M, Carroll, P., Wolf, E, Brem, G, Thoenen, H, Bonhoeffer, T.(1995). Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor. Proc Natl Acad Sci U S A, 92, 8856-8860.
[29] Patterson, S.L., Grover, L.M., Schwartzkroin, P.A., Bothwell, M. (1992). Neurotrophin expression in rat hippocampal slices: a stimulus paradigm inducing LTP in CA1 evokes increases in BDNF and NT-3 mRNAs. Neuron, 9,1081-1088.
[30] Rex, C.S., Lin, C.Y., Kramar, E.A., Chen, L.Y., Gall, C.M., Lynch, G. (2007). Brain-derived neurotrophic factor promotes long-term potentiation-related cytoskeletal changes in adult hippocampus. J Neurosci, 14,3017-3029.
[31] Cui, M.H, Yang, Y, Yang, J.L., Zhang, J.C., Han, H.L., Ma, W.P., Li, H.B., Mao, R.R., Xu, L., Hao, W., Cao, J. (2006). Enriched environment experience overcomes the memory deficits and depressive-like behavior induced by early life stress. Neurosci Letters, 404,208-212.
[32] Duffy, S.N.,Craddock, K.J.,Abel,T., Nguyen, P.V.(2001). Environmental enrichment modifies the PKA-dependence of hippocampal LTP and improves hippocampus-dependent memory. Learn.Mem,8,26-34
[33] Leggio, M.G., Mandolesi, L, Federico, F., Spirito, R, Ricci, B., Gelfo, R, Petrosini,L. (2005). Environmental enrichment promotes improved spatial abilities and enhanced dendritic growth in the rat. Behav.Brain Res, 163,78-90.
[34] Perrot-Sinal, T.S, Kostenuik M.A., Ossenkopp, K.P., Kavaliers, M.(1996). Sex differences in performance in the Morris water maze and the effects of initial nonstationary hidden platform training. Behav Neurosci, 110,1309-1320.
[35] Roof, R.L., & Stein, D.G..(1999). Gender differences in Morris water maze performance depend on task parameters. Physiol Behav, 68,81-86.
[1]袁宝珊,吴宜群.环境铅污染与儿童健康.国外医学卫生学分册,1998,25:193-198.
[2]Burns JM,Baghurst PA,Sawyer MG,et al.Lifetime low-level exposures to environmental lead arid children' s emotional and behavioral development at ages 11-13 years.The Port Pirie Cohort Study.Am J Epidemiol,1999,149:740-749.
[3]沈晓明.儿童铅中毒.北京:人民卫生出版社,1996.
[4].DC Bellinger,H Hu,K Kalaniti,N Thomas,P Rajan,S Sambandam,P Ramaswamy,K Balakrishnan:A pilot study of blood lead levels and neurobehavioral function in children living in Chennai,India.Int J Occup Environ Health 2005,11:138-43.
[5].M De Marco,R Halpern,HM Barros:Early behavioral effects of lead perinatal exposure in rat pups.Toxicology 2005,211:49-58.
[6].MD Ris,KN Dietrich,PA Succop,OG Berger,RL Bornschein:Early exposure to lead and neuropsychological outcome in adolescence.J Int Neuropsychol Soc 2004,10:261-70.
[7].L Schnaas,SJ Rothenberg,MF Flores,S Martinez,C Hernandez,E Osorio,SR Velasco,E Perroni:Reduced intellectual development in children with prenatal lead exposure.Environ Health Perspect 2006,114:791-7.
[8].GA Wasserman,X Liu,D Popovac,P Factor-Litvak,J Kline,C Waternaux,N LoIacono,JH Graziano:The Yugoslavia Prospective Lead Study:contributions of prenatal and postnatal lead exposure.
[9]RL Canfield,CR Henderson,Jr.,DA Cory-Slechta,C Cox,TA Jusko,BP Lanphear:Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter.N Engl J Med 2003,348:1517-26.
[10]HL Needleman,CA Gatsonis:Low-level lead exposure and the IQ of children.A meta-analysis of modern studies.Jama 1990,263:673-8.
[11]Ruan DY,Chen JT,Zhao C,et al.Impairment of long-term potentiation and paired-pulse facilitation in rat hippocampal dentate gyrus following developmental lead exposure in vivo.Brain Res,1998,806:196-201.
[12]Yu SS,Wang M,Li XM,et al.Influences of different developmental periods of taurine supplements on synaptic plasticity in hippocampal CA1area of rats following prenatal and perinatal lead exposure.BMC Dev Biol,2007,7:51-58.
[13]颜崇淮,沈晓明.儿童铅中毒处理中值得注意的问题.中国实用儿科杂志,2006,21:171-173.
[14]Munoz JJ,Roca C,Santos JL,et al.Effect of zinc or S-adenosyl-Lmethionine on long term administration of low doses of lead to rats.Pharmacol Toxicol,1993,73(4):189-191.
[15]Parades SR,Kozicki PA,Batlle AM.S-adenosyl-L-methionine a counter to lead intoxication? Comp Biochem Physiol B,1985,82:751-757.
[16]Paredes SR,Juknat de Geralnik AA,Batlle AM,et al.Beneficial effect of S-adenosyl-L-methionine in lead intoxication.Another approach to clinical therapy.Int J Biochem,1985,17:625-629.
[17]Paredes SR,Fukuda H,Kozicki PA,et al.S-adenosyl-L-methionine and lead intoxication:its therapeutic effect varying the route of administration.Ecotoxicol Environ Saf,1986,12:252-260.
[18]Xie L,Gao Q,Xu H.Ameliorative effect of L-methionine on Pb-exposed mice.Biol Trace Elem Res,2003,93(1/3):227-236.
[19]Kachru DN,Khandelwal S,Tandon SK.Influence of.methionine supplementation in chelation of lead in rats.Biomed Environ Sci,1989,2(3):265-270.
[20]Katz B,Miledi R.The role of calcium in neuromuscular facilitation.J Physiol,1968,195:481-492.
[21]Zhu,D.M.,Wang,M.,She,J.Q.,Yu,K.,Ruan,D.Y.2005.Protection by a taurine supplemented diet from lead-induced deficits of long-term potentiation/depotentiation in dentate gyrus of rats in vivo.Neuroscience.134,215-224.
[22] She, J.Q., Wang, M., Zhu, D.M., Sun, L.G., Ruan,D.Y. 2005. Effect of ganglioside on synaptic plasticity of hippocampus in lead-exposed rats in vivo. Brain. Research. 1060,162-169.
[23]Busselberg, D., Michael, D., Platt, B., 1994. Pb~(2+) reduces voltage- and N-methyl-D-aspartate (NMDA)-activated calcium channel currents. Cell Mol Neurobiol. 14,711-722.
[24] Alkondon, M., Costa, A.C., Radhakrishnan, V., Aronstam, R.S., Albuquerque, E.X., 1990. Selective blockade of NMDA-activated channel currents may be implicated in learning deficits caused by lead. FEBS Lett .261,124-130.
[25] Nakaqawa, K., 1992. Modification by phenobarbital of decreased glutathione content and glutathione S-transferase activity in livers of lead-treated mice. Toxicol Lett. 62,63-71.
[26] Saxena, G, Flora, S.J., 2004. Lead-induced oxidative stress and hematological alterations and their response to combined administration of calcium disodium EDTA with a thiol chelator in rats. J Biochem Mol Toxicol. 18,221-233.
[27] Saxena, G, Pathak, U., Flora, S.J.,2005. Beneficial role of monoesters of meso-2,3-dimercaptosuccinic acid in the mobilization of lead and recovery of tissue oxidative injury in rats. Toxicology. 214,39-56.
[28]Almaguer-Melian W, Cruz-Aguado R, Bergado JA. Synaptic plasticity is impaired in rats with a low glutathione content. Synapse, 2000,38:369-374.
[29] Kannan R, Kuhlenkamp JF, Jeandidier E, et al. Evidence for carrier-mediated transport of glutathione across the blood-brain barrier in the rat. J Clin Invest, 1990,85:2009-2013.
[30]Bliss, T. V., Collingridge, G.L., 1993. A synaptic model of memory:long-term potentiation in the hippocampus. Nature. 361, 31-39.
1. Baydas G., Ozveren F, Akdemir I, et al. (2005). Learning and memory deficits in rats induced by chronic thinner exposure are reversed by melatonin. J Pineal Res 39(1),50-56.
2. Gonenc S, Uysal N, Acikgoz O, et al (2005). Effects of melatonin on oxidative stress and spatial memory impairment induced by acute ethanol treatment in rats. Physiol Res 54(3), 341-348.
3.Bliss T V, Lomo T (1973). Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol (London) 232(2),331-356.
4. Wang S Q, Zhang J L (2004). Blood lead levels of Children in China. J Environ Health 21(6), 355-360 (In Chinese).
5. Pueschel S M (1974). Neurological and psychomotor functions in children with an increased lead burden, Environ Health Perspect 7,13-16.
6. Winneke G, Lilienthal H, Kramer U (1996). The neurobehavioural toxicology and teratology of lead, Arch Toxicol Suppl 18,57-70.
7.Baltaci A K, Bediz C S, Mogulkoc R, et al. (2003). Effect of zinc and melatonin supplementation on cellular immunity in rats with toxoplasmosis. Biol Trace Elem Res 96(1-3), 237-245.
8.Kaya O, Gokdemir K, Kilic M, et al. (2006). Melatonin supplementation to rats subjected to acute swimming exercise: Its effect on plasma lactate levels and relation with zinc. Neuro Endocrinol Lett. 27(1-2), 263-266.
9.Wang L M, Suthana N A, Chaudhury D, et al. (2005). Melatonin inhibits hippocampal long-term potentiation. Eur J Neurosci 22(9), 2231 -2237.
10.Collins D R., Davies S N (1997). Melatonin blocks the induction of long-term potentiation in an N-methyl-D-aspartate independent manner. Brain Res 767(1),162-165.
11.Grant S G, O'Dell T J, Karl K A, et al. (1992). Impaired long term potentiation, spatial learning and hippocampal development in fyn mutant mice. Science 258(5090), 1903-1910.
12. Zhang J Y, Zhang J J, Hao S Y, et al. (1988). Effect of intraventricular injection of the melatonin on hippocampal unit activity and memory behavior in the rat (abstract). Chin J Physiol Sci 4,292.
13.Ying S W, Hao S Y, Zhang J Y, et al. (1989). Effects of microiontophoretically applied melatonin on the electrical activity of neurons in the rat hippocampus. Chin J Appli Physiol 5, 187-193(In Chinese).
14.Rosenstein R E, Cardinali, D P (1986). Melatonin increase in vivo GABA accumulation in rat hypothalamus, cerebullum, cerebral cortex and pineal gland. Brain Res, 398(2),403-406.
15.Zeise M L, Semm P (1985). Melatonin lowers excitability of guinea pig hippocampal neurons in vitro. J Comp Physiol [A] 157(1), 23-29.
16.Kuhlmann A C, McGlothan J L, Guilarte T R (1997). Developmental lead exposure causes spatial learning deficits in adult rats. Neurosci Lett 233(2-3),101-104.
17.Yun S, Lannert H, Hoyer S (2000) Chronic exposure to low-level lead impairs learning ability during aging and energy metabolism in aged rat brain. Arch Gerontol Geriatr 30(3), 199-213.
18.Gilbert M E, Kelly M E, Samsam T E (2005). Chronic developmental lead exposure reduces neurogenesis in adult rat hippocampus but does not impair spatial learning. Toxicol Sci 86(2), 365-374.
19. Jett, D A, Kuhlmann A C, Guilarte T R (1997). Intrahippocampal administration of lead (Pb) impairs performance of rats in the Morris water maze. Pharmacol Biochem Behav 57(1-2),263-269.
20. Yang Y, Ma, Y, Ni L, et al. (2003). Lead exposure through gestation-only caused long-term learning/memory deficits in young adult offspring. Exp Neurol 184(1), 489-495.
21.Ruan D Y, Chen J T, Zhao C et al. (1998). Impairment of long-term potentiation and paired-pulse facilitation in rat hippocampal dentate gyrus following developmental lead exposure in vivo. Brain Res 806(2), 196-201.
22.Zhu D M, Wang M, She J Q et al. (2005). Protection by a taurine supplemented diet from lead-induced deficits of long-term potentiation/depotentiation in dentate gyrus of rats in vivo. Neuroscience 134(1): 215-224.
23.She J Q, Wang M, Zhu D M et al (2005). Effect of ganglioside on synaptic plasticity of hippocampus in lead-exposed rats in vivo. Brain. Res. 1060(1-2), 162-169.
24. Alkondon M, Costa A C, Radhakrishnan V, et al, (1990) Selective blockade of NMDA-activated channel currents may be implicated in learning deficits caused by lead. FEBS Lett 261(1),124-130.
25. Guilarte T R, McGlothan J L (2003). Selective decrease in NR1 subunit splice variant mRNA in the hippocampus of Pb2+-exposed rats: implications for synaptic targeting and cell surface expression of NMDAR complexes. Brain Res Mol Brain Res 113(1-2), 37-43.
26.Xiao C, Gu Y, Zhou C Y (2006). Pb~(2+) impairs GABAergic synaptic transmission in rat hippocampal slices: a possible involvement of presynaptic calcium channels. Brain Res 1088(1), 93-100
2.缪锟,孙亮,于莲珍等.1999.腺苷蛋氨酸治疗慢性酒精性肝病合并重度肝内胆汁瘀积的评估.江苏医药.25(12):940-942.
3.柯伟群.2002.新生儿病理性黄疽病因分析.中华中西医结合杂志,2(9):137-139.
4.刘永泉,樊晶光,1997.驱铅治疗辅助药物的研究进展.国外医学卫生学分册.24,10-11.
5.潘小萍.2006.腺苷蛋氨酸佐治新生儿高胆红素血症.儿科药学杂志.12(6):33-35.
6.沈晓明.1996.儿童铅中毒.北京:人民卫生出版社.
7.王慕邀.2000.儿科学.第5版.北京:人民卫生出版社 117-118.8.谢玲琳,朱长虹,田卫群.2003.L-蛋氨酸驱铅对小鼠体内微量元素的影响.中华劳动卫生职业病杂志.2:108-110.
9.颜崇淮,沈晓明.2006.儿童铅中毒处理中值得注意的问题.中国实用儿科杂志,21(3):171—173.
10.袁宝珊,吴宜群.1998.环境铅污染与儿童健康.国外医学卫生学分册,25:193-198.
11.张频,黄砚青,王雪芬,等.2007.腺苷蛋氨酸对酒精性肝损伤大鼠甲硫氨酸代谢和脂质过氧化的影响.临床肝胆病杂志.23(1):158-161.
12.Agricola R,Dalla Verde G,Urani R,et al.1994.S-adenosyl-L-methionine in the treatment of major depression complicating chronic alcoholism.Curr Ther Res.55:83-92.
13.Alvarez E,Udina C,Guillamat R.1987.Shortening of latency period in depressed patients treated with SAMe and other antidepressant drugs.Cell Biol Rev.S1:103-110.
13.Apte M.2002.Oxidative stress:Does it "initiate" hepatic stellate cell activation or only "perpetuate" the process? J Gastroenterol Hepatol,17:1045-1048.
14. Bell KM, Potkin SG, Carreon D ,et al. 1994.S-adenosylmethionine blood levels in major depression: changes with drug treatment. Acta Neurol Scand Suppl. 154:15—18.
15. Bottiglieri T, Godfrey P, Flynn T, et al. 1990. Cerebrospinal fluid S-adenosylmethionine in depression and dementia:effects of treatment with parenteral and oral S-adenosylmethionine.J Neurol Neurosurg Psychiatry .53:1096-1098.
16 . Bressa GM.1994.S-Adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies. Acta Neurol Scand. 154 (suppl):7-14.
17. Burns JM, Baghurst PA, Sawyer MG,et al. 1999.Lifetime low-level exposures to environmental lead and children' s emotional and behavioral development at ages 11～13 years.The Port Pirie Cohort Study. Am J Epidemiol. 149:740-749.
18. Catalino S, Scarponi S, Cesa F, et al. 1992. Efficacy and safety of intravenous S-Adenosyl-L -Methionine in the mangement of intrahepatic cholestasis of pregnancy. Drugs Invest, 4 (Supp 14): 78-82.
19. Cerutti R, Scichel MP, Perin M, et al. 1993. Psychological distress during puerperium: a novel therapeutic approach using S-adenosylmethionine. Curr Ther Res. 53:707-716.
20. Chawla RK, Lewis FW, Kutner M et al. 1984. Plasma cysteine, cystine, and glutathione in cirrhosis.Gastroenterology. 87, 770-776.
21. David M, Maurizio F. 2002.Role of S-adenosyl-L-methionine in the treatment of depression:a review of the evidence. Am J Chin Nutr. 76(5): 1158S-1161S.
22. Di Rocco A, Rogers JD, Brown R, et al. 2000.S-Adenosyl-methionine improves depression in patients with Parkinson's disease in an open-label clinical trial. Mov Disord. 15:1225-1229.
23. Flora GJ, Seth PK. 1999. Beneficial effects of S-adenosyl-L-methionine on aminolevulinic acid dehydrase,glutathione and lipid peroxidation during acute lead-ethanol administration in mice. Alcohol. 18(2—3): 103—108.
24 . Fontanari D, DiPalma C, Giorgetti G, et al. 1994.Effects of S-adenosyl-L-methionine on cognitive and vigilance functions in elderly. CurrTher Res.55:682-689.
25. Frezza M, Pozzato G , Chiesa L. 1984. Reversal of intrahepatic cholestasis ofpregnancy in women after high dose S2adenosyl2L2methionine administration. Hepatology. 4 (2): 274-278.
26. Hill DB,Deaciuc IV, Nanji AA et al. 1998.Mechanisms of hepatic injury in alcoholic liver disease.Clin Liver Dis. 2: 703-721.
27. Horowitz JH, Rypins EB, Henderson JM et al. 1981. Evidence for impairment of transsulfuration pathway in cirrhosis.Gastroenterology. 81, 668-675.
28. Jiang W, Yang CQ, LiuWB, et al. 2004.Blockage of transforming growth factor β recep tors prevents progression of ig serum- induced rat liver fibrosis. World J Gastroenterol, 10(11) : 1634-1638.
29. Kufferle B, Grunberger J. 1982.Early clinical double-blind study with S-adenosyl-L-methionine: a new potential antidepressant. In: Costa E, Racagni G, eds. Typical and atypical antidepressants. New York: Raven Press. 175-180.
30. Lo Russo A, Monaco M, Pani A, et al. 1994. Efficacy of S-adenosyl methionine in relieving psychologic distress associated with detoxification on opiate abusers. Curr Ther Res. 55:905-913.
31 . Manzillo G, Piccinino F, Surrenti C. 1992. Multicenter. double-blind, placebo-controlled study of intravenous and oral S-adenosyl-L-methionine in cholestatic patients with liver disease. Drug Invest. 4 (supp 14):90-100.
32. McClain CJ, Barve S, Deaciuc I et al. 1999.Cytokines in alcoholic liver disease. Semin Liver Dis 19,205-219.
33. McClain C, Barve S, Joahi-Barve S, et al. 2005. Dysregulated cytokine metabolism, altered hepatic methionine metabolism and proteasome dysfunction in alcoholic liver disease. Alcohol Clin Exp Res, 29(11 Suppl):180S-188S
34. McClain CJ, Hill DB,Song Z,et al. 2002. S-Adenosylmethionin, cytokines, and alcoholic liver disease. Alcohol, 27(3): 185-192.
35. Miccoli L, Porro V, Bertolino A. 1978.Comparison between the antidepressant activity of S-adenosyl-L-methionine (SAMe) and that of some tricyclic drugs. Acta Neurol (Napoli).33:243-255.
36. Morrison LD,Smith DD,Kish SJ. 1996.Brain S-adenosylmethionine levels are severely decreased in Alzheimer's disease. J Neurochem. 67(3): 1328-1331.
37. Munoz JJ,Roca C,Santos JL,et al. 1993. Effect of zinc or S-adenosyl-L-methionine on long term administration of low doses of lead to rats.Pharmacol Toxicol, 73:189—191.
38. Nieto N, Cederbaum AI. 2005.S-adenosylmethionine blocks collagen I production by p reventing TGF beta induction of the COL1A2 promoter. Biol Chem, 280(35) : 30963-309674.
39. Nieto N, Friedman SL, Cederbaum AI. 2002. Cytochrome P450 2E12derived oxygen species mediate paracrine stimulation of collagen I protein synthesis by hepatic stellate cells. J Biol Chem, 277 : 9853-9864
40. Parades SR, Kozicki PA, Batlle AM. 1987.S-adenosyl-L-methionine a counter to lead intoxication? Comp Biochem Physiol B, 1985,82(4): 751 -757.
41. Rodncy LL, Barham SB, Jackob M. 1999.Methionine residues may protect proteins from critical oxidative damage. Mech Ageing Dev. 107;323-332
42. Sougioultzis S, Dalakas E,Hayes PC,et al. 2005. Alcoholic hepatitis:from pathogenesis to treatment. Curr Med Res Opin, 21 (9): 1337-1346.
43 . Spillmann M, Fava M. 1996. S-adenosyl-methionine (ademethionine) in psychiatric disorders. CNS Drugs.6:416-425.
44. Svegliati BG, Ambrosio L, Ferretti G, et al. 1998.Fibrogenic effect of oxidative stress on rat hepatic stellate cells. Hepatology.27: 720-726.
45. Tsai SM, Lee KT, Tsai LY. 2001. Effects of S2adenosyl2L2methionine on liver damage in experimental obstructive jaundice. Kaohsiung J Med Sci ,17 : 455-460.
46. Wang X, Cederbaum AI. 2006.S — adenosyl — L — methionine attenuates hepatotoxicity induced by agonistic Jo2 Fas antibody following CYP2E1 induction in mice. J Pharmacol Exp Ther.317: 44252.
47. Wu D , Cederbaum AI. 2006.Opposite action of S2adenosyl methionine and its metabolites on CYP2E12mediated toxicity in pyrazole2induced rat hepatocytes and HepG2 E47 cells. AmJ Physiol Gastrointest Liver Physiol ,290 : 674-684.
48.Xie L,Gao Q,Xu H.2003.Ameliorative effect of L-methionine on Pb-exposed mice.Biol Trace Elem Res.93(1-3):227-236.
49.Yatsuqi S,Yamamoto T,Ohno.M,et al.1989.Effect of S-adenosyl-L-methionine on impairment of working memory induced in rats by cerebral ischemia and scopolamine.Eur J Pharmacol.166(2):231-239.
1.安继业,姚梅玲,冯彩英等.2007.早期教育对婴幼儿神经心理发育影响的探讨.医药论坛杂志.28(2):16—19
2.鲍秀兰.10～3岁儿童教育的重要性.实用儿科临床杂志.2003,(4):243
3.曹云,邵肖海等,2000.环境刺激对缺氧缺血性脑损伤鼠突触结构的影响,中国生育健康杂志.11(3):104—106.
4.郭建华,满立新,甘晓虹等2007.驱铅合并感觉统合训练治疗感觉统合失调儿童的临床疗效.中国行为医学科学.16(1):35—38.
5.胡君,林秋君,陈燕惠.等.2004.早期干预对脑损伤大鼠学习记忆及神经生长因子的影响.中国心理卫生杂志.18(7):491—494.
6.李亚,吴馥梅.1999.突触后致密结构的一些研究进展.神经解剖学杂志.15(3):293-295.
7.李雪梅,蒲昭霞,周晓军.2008.环境刺激对缺氧缺血性脑损伤新生大鼠海马微管相关蛋白-2表达的影响,中国新生儿科杂志.23(1):15-18
8.李松,洪世欣,王大海,等.2003.早产儿和低体重及小于胎龄儿与脑瘫发生的关系.中华儿科杂志.41:344-347.
9.鲁利群,赵聪敏,蒲昭霞.2006.环境刺激对缺氧缺血性脑损伤大鼠海马巢蛋白表达及学习记忆的影响.第三军医大学学报.28(8):804-806.
10.潘嘉敏.2004.幼儿血铅水平与环境因素的相关性研究.中国妇幼保健.19(16):32—34.
11.施莉萍.2002.如何促进儿童智力发展.现代特殊教育.6:6—7.
12.沈晓明.2006.儿童脑科学研究的临床和教育意义:研究到应用.中国儿童保健杂志.14(1):1.
13.吴馥梅,杜红燕,章子贵.等.1994.突触界面曲率及其生理意义.神经解剖 杂志,10(1):89-92.
14.徐海青,张晓蓉,陈自励.1999.环境因素对早产低体重儿智能发育的影响.中国儿童保健杂志.7(4):235—237.
15.杨玉华.2005.家庭环境对儿童全血铅的影响.微量元素与健康研究.22(1):36—39.
16.Adembri C,Venturi L,Tani A,et al.2006.Neuroprotective effects of propofol in models of cerebral ischemia:inhibition of mitochondrial swelling as a possible mechanism.Anesthesiology.104(1):80-89.
17.Alkondon M.,Costa AC,Radhakrishnan V et al.1990.Selective blockade of
NMDA-activated channel currents may be implicated in learning deficits caused by
lead.FEBS Lett.261,124-130.
18.Aunt JV,Gooper BAB,Today WA.1988.Very low—brith—weight infant at 8and 11 years of age:role of neonatal illness and family status.Pediatrics.82:596-561.
19.Bai G.,Kusiak JW.1995.Functional analysis of the proximal 5-flanking region of the N-methyl-D-aspartate receptor,subunit gene,NMDAR1.J Biol Chem.270:7737-7744.
20.Bai G.,Kusiak JW.1997.Nerve growth factor up-regulate the N-methyl-D-aspartate receptor subunit 1 promotor,in PC12 cells.J Biol Chem.272:5936-5942.
21.Bellinger DC.2000.Effect modification in epidemiologic studies of low-level neurotoxicant exposures and health outcomes.Neurotoxicol.Teratol.22:133-140.
22.Bellinger DC,Leviton A,Waternaux C.et al.1988.Low-level lead exposure,social class,and infant development.Neurotoxicol.Teratol.10:497-503.
23.Bennett JC,McRae PA,Levy LJ et al.2006.Long-term continuous,but not daily,environmental enrichment reduces spatial memory decline in aged male mice.Neurobiol Learn Mem.85(2):139-152.
24.Bleecker ML,Lindgren KN,Ford DP,et al.2002.The interaction of education and cumulative lead exlposue on the Mini-Mental State Examination.J Occup Environ Med.44(6):574-578.
25 . Bona E, Johansson BB, Hagberg H. 1997.Sensorimotor function and neuropathology five or six weeks after hypoxic-ischemia in seven-day-old rats. Pediatr Res. 42: 678-683.
26. Bruno W, Rodrigur G, Christian K, et al. 2004. Recovery from brain injury in animals:relative efficacy of environmental enrichment, physical exercise or formal training(1990-1992).Progress in Neurobiol. 72:167-82.
27. Buchhold B, Mogoanta L, Suofu Y et al. 2007.Environmental enrichment improves functional and neuropathological indices following stroke in young and aged rats.Restor Neurol Neurosci. 25(5-6):467-84o
28. Cui MH, Yang Y, Yang JL et al. Enriched environment experience overcomes the memory deficits and depressive-like behavior induced by early life stress, Neuroscience Letters.2006,404: 208-212.
29. Day JC, Koehl M., Deroche V et al. 1998. Prenatal stress enhances stress- and corticotropin-releasing factor-induced stimulation of hippocampal acetylcholine release in adult rats, Journal of Neuroscience. 18:1886-1892.
30. Duffy SN, Craddock KJ, Abel T et al. 2001. Environmental enrichment modifies the PKA-dependence of hippocampal LTP and improves hippocampus-dependent memory. Learning & Memory. 8: 26-34.
31. Falkenberg T, Mohammed AK, Henriksson B. 1992. Increased expression of brain-derived neurotrophic factor mRNA in rat hippocampus is associated with improved spatial learning and enriched environment. Neuroscience Lett. 138:153-156.
32. Flahelty EG. 1995. Risk of lead poisoning in abused and neglected children.Clin Pediat. 34:128-132.
33. Guilarte, TR, Toscano CD, McGlothan JL et al. 2003. Environmental enrichment neurotrophic factor reverses cognitive and molecular deficits induced by developmental lead exposure. Ann Neurol. 53, 50-56.
34. Gobbo OL, O' Mara SM. 2004.Impact of enriched-environment housing on brain-derived and on cognitive performance after a transientglobal ischemia.Behav Brain Res. 152:231-241.
35. Hanas JS, Rodgers JS, Bantle JA.et al. 1999.Lead inhibition of DNA-binding mechanism of Cys (2) His (2) Zinc finger proteins.Mol Pharmacol. 56:982-988.
36 . Harburger LL, Lambert TJ,Firck KM 2007. Age-dependent effects of environmental enrichment on spatial reference memory in male mice. Behav Brain Res. 185(1):43-48.
37. Kawasaki T, Nishio T, Kawaguchi S, et al. 2001. Spatiotemporal distribution of GAP-43 in the developing rat spinal cord: a histological and quantitative immunofluorescence study. Neurosci Res. 39(3):347-358.
38. Koenig JI., Elmer G.I., Shepard PD et al. 2005.Prenatal exposure to a repeated variable stress paradigm elicits behavioral and neuroendocrinological changes in the adult offspring: potential relevance to schizophrenia. Behavioural Brain Research. 156:251-261.
39. Hayashi A, Nagaoka M, Yamada K et al. 1998.Maternal stress induces synaptic loss and developmental disabilities of offspring. International Journal of Developmental Neuroscience. 16:209-216.
40. Huang EJ, Reichardt LF 2001. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 24: 677-736
41. Kinnunen AK., Koenig JI. and G. Bilbe. 2003. Repeated variable prenatal stress alters pre- and postsynaptic gene expression in the rat frontal pole. Journal of Neurochemistry. 86: 736-748.
42. Koo JW, Park CH, Choi SH.et al. 2003.The postnatal environment can counteract prenatal effects on cognitive ability, cell proliferation, and synaptic protein expression, The FASEB Journal. 17:1556-1558.
43 . Kwon BK, Tetzlaff W. 2001. Spinal cord regeneration; from gene to transplants.Spine. 26(24 Suppl): 13-22.
44. Jodi E. Gresac K, Kristin M. et al. 2007.Life-long environmental enrichment differentially affects the mnemonic response to estrogen in young, middle-aged, and aged female mice.Neurobiol Learn Mem. 88(4):393-408.
45. Lauren L. Harburger, Talley J.et al. 2007.Age-dependent effects of environmental enrichment on spatial reference memory in male mice.Behav Brain Res. 185(1):43-48.
46. Leggio MG, Mandolesi L, Federico F et al. 2005. Environmental enrichment promotes improved spatial abilities and enhanced dendritic growth in the rat. Behavioural Brain Research. 163:78-90.
47. Lemaire V, Lamarque S, Moal ML et al. 2006. Postnatal stimulation of the pups counteracts prenatal stress-induced deficits in hippocampal neurogenesis. Biological Psychiatry. 59:786-792.
48. Liu A,Prenger MS, Norton DD. 2001. Nerve growth factor uses Ras/ERK and phosphatidylinositol 3-kinase cascades to up-regulate the N-methyl-D-aspartate receptor 1 promotor. J Biol Chem. 276:45372-45379.
49. Lordi B. Lordi, Patin V., Protais P.et al. 2000. Chronic stress in pregnant rats: effects on growth rate, anxiety and memory capabilities of the offspring, International Journal of Psychophysiology 37:195-205.
50. Maccari S., Darnaudery M., Morley-Fletcher S et al. 2003. Prenatal stress and long-term consequences: implications of glucocorticoid hormones, Neuroscience and Biobehavioral Reviews. 27:119-127.
51. Mayer SJ. 2005.The early evolution of Jean Piaget 's clinical method. Hist Psychol. 8 (4): 362-382
52. Markus EJ, Petit TL. 1989.Synaptic structural plasticity: role of synaptic shape.3(1):1-11.
53. Melman ST, Nimeh JW,Anbar RD. 1998.Prevalence of elevated blood lead levels in an inner citty pediatric popunation .Environment health perspect. 106:655-657.
54. Morley-Fletcher S, Rea M, Maccari S et al.. 2003. Environmental enrichment during adolescence reverses the effects of prenatal stress on play behaviour and HPA axis reactivity in rats. The European Journal of Neuroscience. 18: 3367-3374.
55. Murakami Y, Furukawa S, Nitta A, et al. 2002. Accumulation of nerve growth factor protein at both rostral and caudal stumps in the transected rat spinal cord.Neurol Sci, 198 (1-2): 63-69.
56. Nihei MK, Desmond NL, McGlothan JL et al. 2000.NMDA receptor subunit changes are associated with Pb~(2+) -induced deficits of LTP and spatial learning. Neuroscienc. 99:233-242.
57. Pascura R, Ftgueroa H. 1996.Effects of preweaning sensornigotor stimulation on behavioral and neuronal development in motor and visual of the rat1 Biol Neonate, 69: 399
58. Rampon C, Jiang CH, Dong H et al. 2000.Effects of environmental enrichment on gene expression in the brain, Proceedings of the National Academy of Sciences of the United States of America. 97:12880-12884.
59. Robinson S, Petelenz K, Li Q, et al.2005.Developmental changes induced by graded prenatal systemic hypoxic-ischemic insults in rats. Neurobiol Dis. 18(3): 568-581.
60. Rzmey CT, Ramey SL. 1998.Prevention of intellectual disabilties: early interventions of imp rove cognitive development 1PrevMed, 27 (2) :224-229
61. Schneider J.S, Lee MH., Anderson DW et al. 2001 .Enriched environment during development is protective against lead-induced neurotoxicity. Brain Research. 896:48-55.
62. Segvoia G,Del Arco A, Garrido P,et al. 2008.Environmental enrichment reduces the response to stress of the cholinergic system in the prefrontal cortex during aiging.Neurochem Int. 52(6): 1198-203.
63. van Praag H,Kempermann G, Gage FH. 2000.Neural consequences of environmental enrichment. Nat Rev Neurosce. 1:191-198.
64. Wolf SA,Kronenberg G, Lehmann K.et al. 2006.Cognitive and physical activity differently modulate disease progression in the amyloid precursor protein (APP)-23 model of Alzheimer's disease.Biol Psychiatry. 60(12):1314-1323.
65 . Wadhwa PD. 2005.Psychoneuroendocrine processes in human pregnancy influence fetal development and health. Psychoneuroendocrinology . 30: 724-743.
66. Weinstock M. 2001 .Alterations induced by gestational stress in brain morphology and behaviour of the offspring. Progress in Neurobiology. 65: 427-451.
67. Weinstock M., Poltyrev T., Schorer-Apelbaum D.et al. 1998.Effect of prenatal stress on plasma corticosterone and catecholamines in response to footshock in rats, Physiology & Behavior. 64: 439-444.
68. Yamauchi T. 2002. Molecular constituents and phosphorylation-dependent regulation of the postsynaptic density .Mass Spectrom Rev., 21 (4):266-286.
69. Yang JL, Han HL, Cao J et al. 2006.Prenatal stress modifies hippocampal synaptic plasticity and spatial learning in young rat offspring. Hippocampus. 16:431-436.
70. Yang J, Hou C, Ma N et al. 2007.Enriched environment treatment restores impaired hippocampal synaptic plasticity and cognitive deficits induced by prenatal chronic stress.Neurobiology of Learning and Memory. 87:257-264.
71.."Zawia NH, Sharan R, Brydie M. 1998. Spl as a target for metal-induced perturbations of transcriptional regulation of developmental brain gene expression. Dev Brain Res. 107:291-298.
72. Zhang XY, Liu AP, Ruan DY. et al. 2002.Effect of developmental lead exposure on the expression of specific NMDA receptor subunit mRNA in the hippocampus of neonatal rats by digoxigenin-labeled in situ hybridization histochemistry. Neurotoxicol Teratol. 24:149-160.
1.胡前胜,董胜章,任铁铃等.1999.儿童齿铅于智商知系的流行病学研究.环境与健康杂志.16(1):16—19.
2.李勇辉.2001.低浓度血铅对儿童神经心理的影响.湖南师范大学社会科学学报.30(S2):340-342.
3.李沛,董胜璋.1996.环境铅接触对儿童智力与行为影响的调查.环境与健康杂志.13(4):158-160.
4.秦锐,刘昔荣,周鸣等.2004.孕期铅暴露不同示标的意义及与婴儿神经行为发育.中国儿童保健杂志,12(2):99-102.
5.苏丽,吴清,李凤芝.2003.孕母中期血铅水平对妊娠结局影响的初探.广东微量元素科学.10(12):28—30.
6.沈晓明,颜崇淮.1996.低水平铅暴露对早期婴儿发育的影响1中华儿科杂志.34(4):255—257.
7.沈晓明 主编.1996.儿童铅中毒[M].北京:人民卫生出版社,:100-101
8.沈彤,朱中平,俞翠莲等.2006.铅暴露对婴幼儿发育商数影响的队列研究,22(8):906—908.
9.王郁文,程舜华;宋秀珍等.1996.铅暴露与儿童行为异常.中华预防医学杂志.30(3):147—152.
10.颜崇淮,沈晓明,敖黎明等.1997.上海市新生儿脐血铅水平及其影响因素.中华预防医学志.31(1):9-12.
11.俞苏蒙,王振刚,陈美娟等.1995.铅污染地区学龄儿童血铅水平与智商及神经行为功能关系的研究.环境与健康杂志.12(4):158-161.
12.张敬旭,符绍莲,胡江等.1997.脐血铅含量与新生儿神经行为发育的关系.中华预防医学杂志.31(4):215-217.
13.Belling D,Leviton A1987.Longitudinai analgses of prenatal lead exposure and postnatal lead exposure and early connitive development.N Eng L J Med.316:1037
14. Bellinger DC, Stilfs KM, Needleman HL, 1992.Low-level lead exposure, intelligence and academic achievement: a long-term follow-up study. Pediatrics, 90:855-861.
15. Busselberg D, Platt B, Michael D,et al. 1994. Mammalian voltage-activated calcium channel currents are blocked by Pb~(++),Zn~(++),and Al~(3+). J Neurophysiol 71: 234-245.
16. Canfield RL, Henderson CR, Cory - Slechta DA, et al. 2003. Intellectual impairment in children with blood lead concentrations below 10 μg per eciliter. N Engl J Med. 17(16): 1517-1526.
17. Environmental Protection Agency, 1986. Air Quality Criteria for Lead, Office of Health and Environmental Assessment. Research Trangle Park. NC.
18. Finkelstein Y, Sternfeld M, Flechter S. 1990. Septal dopaminergic-chilinergic interactions during stress. Stress Med. 6:3-7.
19 . Finkelstein Y, Markowitz ME, Rosen JF. 1998.Low-level lead-induced neurotoxicity in children: an update on central nevous system effects(Review). Brain Res Rev, 168-176.
20. Gardella C. 2001. Lead exposure in pregnancy:a review of the literature and argument for routine prenatal screening. Obstet. Gynecol. Surv. 56(4):231-238.
21. Ge SY, Ruan DY, Yu K, et al. 2001.Effects of Fe~(2+) on ion channels:Na~+ channel, delayed rectified and transient outward K~+ channels. Food Chem Toxicol. 39:1271-1278.
22. Gomaa A, Hu H, Bellinger D. et al. 2002.Maternal bone lead as anlindependent risk factor for fetal neurotoxicity: A p rospectivestudy. Pediatrics. 110: 110-118.
23. Guilarte TR, RC Miceli. 1992.Age-dependent effects of lead on [3H]MK-801 binding to the NMDA receptor-gated ionophore: in vitro and in vivo studies. Neurosci Lett. 148:27-30.
24. Hansen O, Trillngsgaard A, Beese I et al. 1987.Neuropsychological study of children with elevated dentine lead level. In Lindberg S, Hutchinson T(Eds.) Proceedings of the 6th International Conference on Heavy Metals in the Environment, CEP Consultants. Edinburgh 54-57.
25. Herschkowitz N, 1988. Brain development in the fetus, neonate and infant. Biol Neonate. 54:1-19.
26. Hunter J,Urbanowicz MA, Yule W,et al. 1985. Automated testing of reaction time and its assiciation with lead in children. Int. Arch. Occup. Enviro. Health. 57:27-34.
27. Ishihara K, Alkondon M, Montes JG et al. 1995. Ontogenically related properties of N-methyl-D-aspartate receptors in rat hippocampal neuros and the age-specific sensitivity of developing neurons to lead. J Pharmacol Exp Ther. 273:1459-1470.
28. Jett DA, Kuhlmann AC, Guilarte TR. 1997. Intrahippocampal administration of lead (Pb) impairs performance of rats in the Morris water maze. Pharmacol Biochem Behav.57(1-2):263-269.
29. Jett DA, Kuhlmann AC, Farmer SJ et al. 1997. Age-dependent effects of developmental lead exposure on performance in the Morris water maze. Pharmacol Biochem Behav . 57(1-2):271-279.
30. Kuhlmann, AC, McGlothan, JL, Guilarte, TR. 1997.Developmental lead exposure causes spatial learning deficits in adult rat. Neurosci Lett. 233:101-104.
31. Lasley SM. 1992. Regulation of dopaminergic activity, but not tyrosine hydroxylase, is diminished after chronic inorganiclead exposure. NeuroToxicology. 13:625-636.
32. LeMoal M, Simon H. 1991.Mesocorticolimbic dopaminergic network: functional and regulatory roles. Physiol.Rev. 17:155-234.
33. Mayfield S. 1983. Language and speech behaviors of children with undue lead absorption: a review of the literature. J Speech Hear Res. 26:362-378.
34. Minnema DJ. 1988.Calcium influx and neurotransmitter release from rat hippocampal synaptosomes exposed to lead. Toxicol App Pharmacol.92,351-357.
35. Needleman HL. 1992. Effects of low levels of lead exposure. Science. 256:294-295.
36. Needleman HL, Landrigan PJ. 2004. What level of lead in blood is toxic for a child. Am J Public Health. 94: 8-9.
37. Otto DA, Fox DA. 1993.Auditory and visual dysfunction following lead exposure. Neurotoxicology.14:191-208.
38. Patel AB,MamtaniMR, Thakre TP et al. 2006. Association of umbilicalcord blood lead with neonatal behavior at varying levels of exposure. Behav Brain Funct. 2:22-28.
39. Pirkle JL. 1994.The decline in blood lead levels in the United StateslJAMA. 272: 284
40. Pocock SJ, Smith M, Baghurst P. 1994. Encironmental lead and children's entelligence:a systematic review of ht epidemiological evidence. BMJ. 309:1189-1197.
41. Schwartz J. 1993 .Beyond LOEL's p-values and vote counting: methods for looking at the shapes and strength of associations. Neurotoxicology . 14:237-248.
42. Schwartz J , Otto DA. 1987.Blood lead, hearing thresholds and neurobehavioral development in children and youth. Arch Environ.Health 42:153-160.
43 . Schwartz J,Otto DA. 1991. Lead and minor hearing impairment. Arch. Environ.Health 46:300-305.
44. Richard L, Canfield Ph.D. 2003.Intellectual impairment in children with blood lead concentrations below 10 μg/dl.The New England Journal of Medicine. 348(16): 1517-1523
4.5. Rosen JF.1992.Effects of low levels of lead exposure. Science. 256(1):294—299.
46. Ruan DY,Chen JT,Zhao C, et al.1998.Impairment of long-term potentiation and paired-pulse facilitation in rat hippocampal dentate gyms following developmental lead exposure in vivo. Brain Res. 806:196-201.
47. Schanne FA, Long GL, Rosen JF. 1997.Lead induced rise in intracellular free calcium in mediated through protein kinase C in osteoblastic bone cells. Biochem BiophysActa 1360:247-254.
48. Shen XM, Rosen JF, Guo D, et al. 1996. Childhood lead poisoning in China. Sci Total Enviro. 181:101-109.
49. Shellenberger M, 1998.Effects of early lead exposure on neurotransmitter systems in the brain: a review with commentary. Neurotoxicol 45,117-122.
50 . Sibergeld EK, Goldberg AM, 1975. Pharmacological and neurochemical
investigations of lead induced hyperactivity.. Neuropharmacology . 14:434-444.
51. Smith M. 1989.The effects of low- level lead exposure on children In:Smith MA, Grant LD.Eds.Lead Exposure and Child Development: An Internation Assessment.Dordrecht: Kluwer Academic Publishers:3-47
52. Sui L,Ge SY, Ruan DY, et al. 2000. Age-related impairment of long-term depression in area CA1 and dentate gyrus of rat hippocampus following developmental lead exposure in vitro. Neurotoxicol Teratol. 22:381-387.
53. Ujihara H, Sasa M, Ban T. 1995.Selective blockade of P-type calcium channels by lead in cultured hippocampal neurons. Jpn J Pharmacol. 67:267-269.
54. Winneke G, Beginn U, Ewert T,et al. 1985. Comparing the effects of perinatal and later childhood lead exposure on neuropsychological outcome. Environ. Res. 38:155-167.
55. Xu YZ, Ruan DY, Wu Y, et al. 1998.Nitric oxide affects LTP in area CA1 and CA3 of hippocampus in low-level lead-exposed rat.Neurotoxicol Teratol. 20:69-73.
56. Yang Y,Ma Y,Ni L et al. 2003. Lead exposure through gestation-only caused long-term learning/memory deficits in young adult offspring.Experimental Neurology. 184:489-495.
57. Zhao WF,Ruan DY, Xu YZ, et al. 1999. The effects of chronic lead exposure on long-term depression in area CA1 and dentate gyrus of rat hippocampus in vitro. Brain Res. 818:153-159.
[1] Khan, N.Z., & Khan,A.H. (1999).Lead poisoning and psychomotor delay in Bangladeshi children. Lancet, 353, 754.
[2] Mushak, P., Davis, J.M., Crocetti, A.F., Grant, L.D. (1989). Prenatal and postnatal effects of low-level lead exposure: integrated summary of a report to the US Congress on childhood lead poisoning. Environ Res, 50, 11-36.
[3] Winneke, G, Lilienthal, H., Kramer, U. (1996). The neurobehavioural toxicology and teratology of lead, Arch.Toxicol. 18(Suppl.),57-70
[4] Yang, Y, Ma, Y, Ni, L., Zhao, S., Li, L, Zhang, J, Fan, M., Liang, C, Cao, J., Xu, L.(2003).Lead exposure through gestation-only caused long-term learning/memory deficits in young adult offspring, Experimental Neurology, 184, 489-495.
[5] Kuhlmann, A.C, McGlothan, J.L., Guilarte, T.R. (1997). Developmental lead exposure causes spatial learning deficits in adult rat. Neurosci Lett, 233,101-104.
[6] Alfano, D.P., Petit,T.L.(1982).Neonatal lead exposue alters the dendritic development of hippocampal dentate granule cells. Exp. Neurol,75,275-288
[7] Petit, T.L., Alfano, D.P., LeBoutillier J.C.(1983).Early lead exposure and the hippocampus :a review and recent advance, Neurotoxicology, 4,79-94
[8] Bellinger,D.C. (2000). Effect modification in epidemiology studies of low-level neurotoxicant exposure and health outcomes, Neurotoxicol.Teratol.22,133-140
[9] Bellinger,D.C, Leviton, A., Waternaux ,C.,Needleman ,H., Rabinowitz M.M.(1988). Low-level lead exposure , social class, and infant development. Neurotoxicol.Teratol 10,497-503
[10] Fox, C, Merali,Z., Harrison, C.(2006).Therapeutic and protective effect of environmental enrichment against psychogenic and neurogenic stress. Behav.Brain Res,175,l-8
[11]Schneider, J.S., Lee, M.H., Anderson, D.W., Zuck, L., Lidsky, T. I. (2001). Enriched environment during development is protective against lead-induced neurotoxicity. Brain Research, 896, 48-55.
[12]Guilarte, T.R., Toscano, C.D., McGlothan, J. L, Weaver, S.A. (2003). Environmental enrichment reverses cognitive and molecular deficits induced by developmental lead exposure. Ann Neurol,53, 50-56.
[13] Bliss, T. V., & Collingridge, G. L. (1993). A synaptic model of memory:long-term potentiation in the hippocampus. Nature, 361,31 -39.
[14] Ruan, D.Y., Chen, J.T., Zhao, C, Xu,Y.Z., Wang, M., Zhao,W.F. (1998). Impairment of long-term potentiation and paired-pulse facilitation in rat hippocampal dentate gyrus following developmental lead exposure in vivo. Brain Res, 806,196-201.
[15] She, J.Q, Wang, M., Zhu, D.M., Sun, L.G., Ruan,D.Y. (2005). Effect of ganglioside on synaptic plasticity of hippocampus in lead-exposed rats in vivo. Brain. Research, 1060,162-169.
[16] Zhu, D.M., Wang, M., She, J.Q., Yu, K., Ruan, D.Y. (2005). Protection by a taurine supplemented diet from lead-induced deficits of long-term potentiation/depotentiation in dentate gyrus of rats in vivo. Neuroscience,134, 215-224.
[17] Alkondon, M., Costa, A.C., Radhakrishnan, V., Aronstam, R.S., Albuquerque, E.X. (1990). Selective blockade of NMDA-activated channel currents may be implicated in learning deficits caused by lead. FEBS Lett, 261,124-130.
[18] Guilarte,T.R., & Miceli,R.C. (1992). Age-dependent effects of lead on [~3H] MK-801 binding to the NMDA receptor-gated ionophore: in vitro and in vivo studies. Neurosci Letters, 148,27-30.
[19] Nihei, M.K., Desmond, N.L., McGlothan, J.L. Kuhlmann A.C, Guilarte T.R. (2000). NMDA receptor subunit changes are associated with Pb~(2+) -induced deficits of LTP and spatial learning. Neuroscienc, 99,233-242.
[20] Zhang, X.Y., Liu,A.P., Ruan, D.Y, Liu, J. (2002). Effect of developmental lead exposure on the expression of specific NMDA receptor subunit mRNA in the hippocampus of neonatal rats by digoxigenin-labeled in situ hybridization histochemistry. Neurotoxicol Teratol, 24,149-160.
[21]Bai, G.,Kusiak J.W.(1995).Functional analysis of the proximal 5-flanking region of the N-methyl-D-aspartate receptor subunit gene, NMDAR1. J Biol Chem.270,7737-7744.
[22] Hanas,.J.S.,Rodgers, J.S, Bantle, J.A.,Cheng ,Y.G.(1999). Lead inhibition of DNA-binding mechanism of Cys2His2 Zinc finger proteins.Mol Pharmacol.56,982-988.
[23]Zawia N.H., Sharan R., Brydie M.(1998). Sp1 as a target for metal-induced perturbations of transcriptional regulation of developmental brain gene expression. Dev Brain Res. 107,291-298.
[24] van Praag H., Kempermann G, Gage F.H.(2000). Neural consequences of environmental enrichment. Nat Rev Neurosce. 1,191-198.
[25]Falkenberg T., Mohammed A.K., Henriksson B.(1992). Increased expression of brain-derived neurotrophic factor mRNA in rat hippocampus is associated with improved spatial learning and enriched environment. Neuroscience Lett 138,153-156.
[26]Bai G, Kusiak J.W.(1997).Nerve growth factor up-regulate the N-methyl-D-aspartate receptor subunit 1 promotor in PC12 cells. J Biol Chem.272,5936-5942.
[27] Liu A.,Prenger M.S., Norton DD.(2001). Nerve growth factor uses Ras/ERK and phosphatidylinositol 3-kinase cascades to up-regulate the N-methyl-D-aspartate receptor 1 promotor. J Biol Chem. 276,45372-45379.
[28]Korte, M, Carroll, P., Wolf, E, Brem, G, Thoenen, H, Bonhoeffer, T.(1995). Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor. Proc Natl Acad Sci U S A, 92, 8856-8860.
[29] Patterson, S.L., Grover, L.M., Schwartzkroin, P.A., Bothwell, M. (1992). Neurotrophin expression in rat hippocampal slices: a stimulus paradigm inducing LTP in CA1 evokes increases in BDNF and NT-3 mRNAs. Neuron, 9,1081-1088.
[30] Rex, C.S., Lin, C.Y., Kramar, E.A., Chen, L.Y., Gall, C.M., Lynch, G. (2007). Brain-derived neurotrophic factor promotes long-term potentiation-related cytoskeletal changes in adult hippocampus. J Neurosci, 14,3017-3029.
[31] Cui, M.H, Yang, Y, Yang, J.L., Zhang, J.C., Han, H.L., Ma, W.P., Li, H.B., Mao, R.R., Xu, L., Hao, W., Cao, J. (2006). Enriched environment experience overcomes the memory deficits and depressive-like behavior induced by early life stress. Neurosci Letters, 404,208-212.
[32] Duffy, S.N.,Craddock, K.J.,Abel,T., Nguyen, P.V.(2001). Environmental enrichment modifies the PKA-dependence of hippocampal LTP and improves hippocampus-dependent memory. Learn.Mem,8,26-34
[33] Leggio, M.G., Mandolesi, L, Federico, F., Spirito, R, Ricci, B., Gelfo, R, Petrosini,L. (2005). Environmental enrichment promotes improved spatial abilities and enhanced dendritic growth in the rat. Behav.Brain Res, 163,78-90.
[34] Perrot-Sinal, T.S, Kostenuik M.A., Ossenkopp, K.P., Kavaliers, M.(1996). Sex differences in performance in the Morris water maze and the effects of initial nonstationary hidden platform training. Behav Neurosci, 110,1309-1320.
[35] Roof, R.L., & Stein, D.G..(1999). Gender differences in Morris water maze performance depend on task parameters. Physiol Behav, 68,81-86.
[1]袁宝珊,吴宜群.环境铅污染与儿童健康.国外医学卫生学分册,1998,25:193-198.
[2]Burns JM,Baghurst PA,Sawyer MG,et al.Lifetime low-level exposures to environmental lead arid children' s emotional and behavioral development at ages 11-13 years.The Port Pirie Cohort Study.Am J Epidemiol,1999,149:740-749.
[3]沈晓明.儿童铅中毒.北京:人民卫生出版社,1996.
[4].DC Bellinger,H Hu,K Kalaniti,N Thomas,P Rajan,S Sambandam,P Ramaswamy,K Balakrishnan:A pilot study of blood lead levels and neurobehavioral function in children living in Chennai,India.Int J Occup Environ Health 2005,11:138-43.
[5].M De Marco,R Halpern,HM Barros:Early behavioral effects of lead perinatal exposure in rat pups.Toxicology 2005,211:49-58.
[6].MD Ris,KN Dietrich,PA Succop,OG Berger,RL Bornschein:Early exposure to lead and neuropsychological outcome in adolescence.J Int Neuropsychol Soc 2004,10:261-70.
[7].L Schnaas,SJ Rothenberg,MF Flores,S Martinez,C Hernandez,E Osorio,SR Velasco,E Perroni:Reduced intellectual development in children with prenatal lead exposure.Environ Health Perspect 2006,114:791-7.
[8].GA Wasserman,X Liu,D Popovac,P Factor-Litvak,J Kline,C Waternaux,N LoIacono,JH Graziano:The Yugoslavia Prospective Lead Study:contributions of prenatal and postnatal lead exposure.
[9]RL Canfield,CR Henderson,Jr.,DA Cory-Slechta,C Cox,TA Jusko,BP Lanphear:Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter.N Engl J Med 2003,348:1517-26.
[10]HL Needleman,CA Gatsonis:Low-level lead exposure and the IQ of children.A meta-analysis of modern studies.Jama 1990,263:673-8.
[11]Ruan DY,Chen JT,Zhao C,et al.Impairment of long-term potentiation and paired-pulse facilitation in rat hippocampal dentate gyrus following developmental lead exposure in vivo.Brain Res,1998,806:196-201.
[12]Yu SS,Wang M,Li XM,et al.Influences of different developmental periods of taurine supplements on synaptic plasticity in hippocampal CA1area of rats following prenatal and perinatal lead exposure.BMC Dev Biol,2007,7:51-58.
[13]颜崇淮,沈晓明.儿童铅中毒处理中值得注意的问题.中国实用儿科杂志,2006,21:171-173.
[14]Munoz JJ,Roca C,Santos JL,et al.Effect of zinc or S-adenosyl-Lmethionine on long term administration of low doses of lead to rats.Pharmacol Toxicol,1993,73(4):189-191.
[15]Parades SR,Kozicki PA,Batlle AM.S-adenosyl-L-methionine a counter to lead intoxication? Comp Biochem Physiol B,1985,82:751-757.
[16]Paredes SR,Juknat de Geralnik AA,Batlle AM,et al.Beneficial effect of S-adenosyl-L-methionine in lead intoxication.Another approach to clinical therapy.Int J Biochem,1985,17:625-629.
[17]Paredes SR,Fukuda H,Kozicki PA,et al.S-adenosyl-L-methionine and lead intoxication:its therapeutic effect varying the route of administration.Ecotoxicol Environ Saf,1986,12:252-260.
[18]Xie L,Gao Q,Xu H.Ameliorative effect of L-methionine on Pb-exposed mice.Biol Trace Elem Res,2003,93(1/3):227-236.
[19]Kachru DN,Khandelwal S,Tandon SK.Influence of.methionine supplementation in chelation of lead in rats.Biomed Environ Sci,1989,2(3):265-270.
[20]Katz B,Miledi R.The role of calcium in neuromuscular facilitation.J Physiol,1968,195:481-492.
[21]Zhu,D.M.,Wang,M.,She,J.Q.,Yu,K.,Ruan,D.Y.2005.Protection by a taurine supplemented diet from lead-induced deficits of long-term potentiation/depotentiation in dentate gyrus of rats in vivo.Neuroscience.134,215-224.
[22] She, J.Q., Wang, M., Zhu, D.M., Sun, L.G., Ruan,D.Y. 2005. Effect of ganglioside on synaptic plasticity of hippocampus in lead-exposed rats in vivo. Brain. Research. 1060,162-169.
[23]Busselberg, D., Michael, D., Platt, B., 1994. Pb~(2+) reduces voltage- and N-methyl-D-aspartate (NMDA)-activated calcium channel currents. Cell Mol Neurobiol. 14,711-722.
[24] Alkondon, M., Costa, A.C., Radhakrishnan, V., Aronstam, R.S., Albuquerque, E.X., 1990. Selective blockade of NMDA-activated channel currents may be implicated in learning deficits caused by lead. FEBS Lett .261,124-130.
[25] Nakaqawa, K., 1992. Modification by phenobarbital of decreased glutathione content and glutathione S-transferase activity in livers of lead-treated mice. Toxicol Lett. 62,63-71.
[26] Saxena, G, Flora, S.J., 2004. Lead-induced oxidative stress and hematological alterations and their response to combined administration of calcium disodium EDTA with a thiol chelator in rats. J Biochem Mol Toxicol. 18,221-233.
[27] Saxena, G, Pathak, U., Flora, S.J.,2005. Beneficial role of monoesters of meso-2,3-dimercaptosuccinic acid in the mobilization of lead and recovery of tissue oxidative injury in rats. Toxicology. 214,39-56.
[28]Almaguer-Melian W, Cruz-Aguado R, Bergado JA. Synaptic plasticity is impaired in rats with a low glutathione content. Synapse, 2000,38:369-374.
[29] Kannan R, Kuhlenkamp JF, Jeandidier E, et al. Evidence for carrier-mediated transport of glutathione across the blood-brain barrier in the rat. J Clin Invest, 1990,85:2009-2013.
[30]Bliss, T. V., Collingridge, G.L., 1993. A synaptic model of memory:long-term potentiation in the hippocampus. Nature. 361, 31-39.
1. Baydas G., Ozveren F, Akdemir I, et al. (2005). Learning and memory deficits in rats induced by chronic thinner exposure are reversed by melatonin. J Pineal Res 39(1),50-56.
2. Gonenc S, Uysal N, Acikgoz O, et al (2005). Effects of melatonin on oxidative stress and spatial memory impairment induced by acute ethanol treatment in rats. Physiol Res 54(3), 341-348.
3.Bliss T V, Lomo T (1973). Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol (London) 232(2),331-356.
4. Wang S Q, Zhang J L (2004). Blood lead levels of Children in China. J Environ Health 21(6), 355-360 (In Chinese).
5. Pueschel S M (1974). Neurological and psychomotor functions in children with an increased lead burden, Environ Health Perspect 7,13-16.
6. Winneke G, Lilienthal H, Kramer U (1996). The neurobehavioural toxicology and teratology of lead, Arch Toxicol Suppl 18,57-70.
7.Baltaci A K, Bediz C S, Mogulkoc R, et al. (2003). Effect of zinc and melatonin supplementation on cellular immunity in rats with toxoplasmosis. Biol Trace Elem Res 96(1-3), 237-245.
8.Kaya O, Gokdemir K, Kilic M, et al. (2006). Melatonin supplementation to rats subjected to acute swimming exercise: Its effect on plasma lactate levels and relation with zinc. Neuro Endocrinol Lett. 27(1-2), 263-266.
9.Wang L M, Suthana N A, Chaudhury D, et al. (2005). Melatonin inhibits hippocampal long-term potentiation. Eur J Neurosci 22(9), 2231 -2237.
10.Collins D R., Davies S N (1997). Melatonin blocks the induction of long-term potentiation in an N-methyl-D-aspartate independent manner. Brain Res 767(1),162-165.
11.Grant S G, O'Dell T J, Karl K A, et al. (1992). Impaired long term potentiation, spatial learning and hippocampal development in fyn mutant mice. Science 258(5090), 1903-1910.
12. Zhang J Y, Zhang J J, Hao S Y, et al. (1988). Effect of intraventricular injection of the melatonin on hippocampal unit activity and memory behavior in the rat (abstract). Chin J Physiol Sci 4,292.
13.Ying S W, Hao S Y, Zhang J Y, et al. (1989). Effects of microiontophoretically applied melatonin on the electrical activity of neurons in the rat hippocampus. Chin J Appli Physiol 5, 187-193(In Chinese).
14.Rosenstein R E, Cardinali, D P (1986). Melatonin increase in vivo GABA accumulation in rat hypothalamus, cerebullum, cerebral cortex and pineal gland. Brain Res, 398(2),403-406.
15.Zeise M L, Semm P (1985). Melatonin lowers excitability of guinea pig hippocampal neurons in vitro. J Comp Physiol [A] 157(1), 23-29.
16.Kuhlmann A C, McGlothan J L, Guilarte T R (1997). Developmental lead exposure causes spatial learning deficits in adult rats. Neurosci Lett 233(2-3),101-104.
17.Yun S, Lannert H, Hoyer S (2000) Chronic exposure to low-level lead impairs learning ability during aging and energy metabolism in aged rat brain. Arch Gerontol Geriatr 30(3), 199-213.
18.Gilbert M E, Kelly M E, Samsam T E (2005). Chronic developmental lead exposure reduces neurogenesis in adult rat hippocampus but does not impair spatial learning. Toxicol Sci 86(2), 365-374.
19. Jett, D A, Kuhlmann A C, Guilarte T R (1997). Intrahippocampal administration of lead (Pb) impairs performance of rats in the Morris water maze. Pharmacol Biochem Behav 57(1-2),263-269.
20. Yang Y, Ma, Y, Ni L, et al. (2003). Lead exposure through gestation-only caused long-term learning/memory deficits in young adult offspring. Exp Neurol 184(1), 489-495.
21.Ruan D Y, Chen J T, Zhao C et al. (1998). Impairment of long-term potentiation and paired-pulse facilitation in rat hippocampal dentate gyrus following developmental lead exposure in vivo. Brain Res 806(2), 196-201.
22.Zhu D M, Wang M, She J Q et al. (2005). Protection by a taurine supplemented diet from lead-induced deficits of long-term potentiation/depotentiation in dentate gyrus of rats in vivo. Neuroscience 134(1): 215-224.
23.She J Q, Wang M, Zhu D M et al (2005). Effect of ganglioside on synaptic plasticity of hippocampus in lead-exposed rats in vivo. Brain. Res. 1060(1-2), 162-169.
24. Alkondon M, Costa A C, Radhakrishnan V, et al, (1990) Selective blockade of NMDA-activated channel currents may be implicated in learning deficits caused by lead. FEBS Lett 261(1),124-130.
25. Guilarte T R, McGlothan J L (2003). Selective decrease in NR1 subunit splice variant mRNA in the hippocampus of Pb2+-exposed rats: implications for synaptic targeting and cell surface expression of NMDAR complexes. Brain Res Mol Brain Res 113(1-2), 37-43.
26.Xiao C, Gu Y, Zhou C Y (2006). Pb~(2+) impairs GABAergic synaptic transmission in rat hippocampal slices: a possible involvement of presynaptic calcium channels. Brain Res 1088(1), 93-100
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |