不同剂量异氟醚对中年小鼠认知功能及海马MBP和pNF-H表达的影响
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摘要
目的:探讨异氟醚对中年小鼠认知功能及海马髓磷脂碱性蛋白(MBP, myelin basic protein)和磷酸化神经丝重亚单位(pNF-H,phosphorylated neurofilament heavy chain)表达的影响。方法:给予中年小鼠不同浓度的异氟醚处理,实验分为对照组和异氟醚处理组(0.5ISO,1.0ISO,1.5ISO),其中异氟醚组小鼠细胞分别给予0.5 MAC,1.0 MAC和1.5 MAC三个浓度的异氟醚处理4小时,对照组给予O_2处理4小时,随后通过水迷宫测试检测其学习记忆能力变化,通过免疫荧光检测海马形态结构及髓鞘相关蛋白MBP和pNF-H表达变化。结果:与对照组相比,(1)类临床浓度的异氟醚处理不影响中年小鼠的自发运动能力(总运动距离:sham:7275.17±1732.58; 0.5ISO:8057.58±1732.58; 1.0ISO:7540.98±1401.61; 1.5ISO:8243.79±1257.65;运动速度:sham:116.75±22.35; 0.5ISO:135.45±32.84; 1.0ISO:130.16±21.38; 1.5ISO:142.31±20.58),但1.0 MAC和1.5 MAC的异氟醚处理明显降低了中年小鼠在水迷宫目标象限的活动时间百分比(sham:58.62±13.70; 0.5ISO:48.92±7.22; 1.0ISO:31.23±13.16; 1.5ISO:30.29±15.76)(P <0.05),且高浓度异氟醚作用强于低浓度异氟醚;(2) 1.0 MAC和1.5 MAC的异氟醚处理明显下调了海马的MBP和p NF-H表达(MBP:sham:60.48±8.20; 0.5ISO:56.69±7.86; 1.0ISO:40.15±4.50; 1.5ISO:31.66±5.46; pNF-H:sham:62.23±9.45; 0.5ISO:55.47±6.98; 1.0ISO:40.16±6.97; 1.5ISO:30.94±5.89)(P <0.05),造成了小鼠海马髓鞘结构损伤,且高浓度损伤强于低浓度。结论:异氟醚可能通过下调中年小鼠海马MBP和pNF-H表达,破坏海马髓鞘完整性而损伤小鼠的学习认知能力。
Objective: To investigate the effect of isoflurane(ISO) on the cognitive function and the expression of myelin basic protein(MBP)and phosphorylated neurofilament heavy polypeptide(pNF-H) in the hippocampus of Middle-aged mice. Methods:Twenty-four 8-month-old mice were divided into control and isoflurane groups(0.5ISO, 1.0ISO and 1.5ISO): control group was treated with O_2 for 4 hours and isoflurane treatment groups(0.5ISO, 1.0ISO and 1.5ISO) were treated with 0.5 MAC, 1.0 MAC and 1.5 MAC of isoflurane for 4 hours respectively(n = 6 for each group). After 24 hours of isoflurane treatment, cognitive function was determined by Morris Water Maze(MWM) test, and then mice were perfused and the expression of MBP and pNF-H in the hippocampus were detected by immumofluorescence method. Results: Compared with the control(sham: 0.53 ±0.14),(1) 1.0 MAC(0.31 ±0.13) and 1.5 MAC(0.30 ± 0.16) isoflurane treatment significantly decreased the time spent in target quadrant with the platform of hippocampus of Middle-aged mice(P<0.05);(2) 1.0 MAC and 1.5 MAC isoflurane treatment significantly decreased the expression of MBP( sham: 60.48±8.20; 0.5 ISO: 56.69 ±7.86; 1.0 ISO: 40.15 ±4.50; 1.5 ISO: 31.66 ±5.46) and pNF-H(sham: 62.23 ±9.45; 0.5 ISO: 55.47 ±6.98;1.0 ISO: 40.16 ±6.97; 1.5 ISO: 30.94 ±5.89) in hippocampus of Middle-aged mice(P<0.05). Conclusion: Isoflurane exposure disturbed the expression of MBP and pNF-H in the hippocampus and induced memory impairment in middle-aged mice
Objective: To investigate the effect of isoflurane(ISO) on the cognitive function and the expression of myelin basic protein(MBP)and phosphorylated neurofilament heavy polypeptide(pNF-H) in the hippocampus of Middle-aged mice. Methods:Twenty-four 8-month-old mice were divided into control and isoflurane groups(0.5ISO, 1.0ISO and 1.5ISO): control group was treated with O_2 for 4 hours and isoflurane treatment groups(0.5ISO, 1.0ISO and 1.5ISO) were treated with 0.5 MAC, 1.0 MAC and 1.5 MAC of isoflurane for 4 hours respectively(n = 6 for each group). After 24 hours of isoflurane treatment, cognitive function was determined by Morris Water Maze(MWM) test, and then mice were perfused and the expression of MBP and pNF-H in the hippocampus were detected by immumofluorescence method. Results: Compared with the control(sham: 0.53 ±0.14),(1) 1.0 MAC(0.31 ±0.13) and 1.5 MAC(0.30 ± 0.16) isoflurane treatment significantly decreased the time spent in target quadrant with the platform of hippocampus of Middle-aged mice(P<0.05);(2) 1.0 MAC and 1.5 MAC isoflurane treatment significantly decreased the expression of MBP( sham: 60.48±8.20; 0.5 ISO: 56.69 ±7.86; 1.0 ISO: 40.15 ±4.50; 1.5 ISO: 31.66 ±5.46) and pNF-H(sham: 62.23 ±9.45; 0.5 ISO: 55.47 ±6.98;1.0 ISO: 40.16 ±6.97; 1.5 ISO: 30.94 ±5.89) in hippocampus of Middle-aged mice(P<0.05). Conclusion: Isoflurane exposure disturbed the expression of MBP and pNF-H in the hippocampus and induced memory impairment in middle-aged mice
引文
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[2]Wang H L,Liu H,Xue Z G,et al.Minocycline attenuates postoperative cognitive impairment in aged mice by inhibiting microglia activation[J].J Cell Mol Med,2016,20(9):1632-1639
[3]Culley D J,Boyd J D,Palanisamy A,et al.Isoflurane decreases selfrenewal capacity of rat cultured neural stem cells[J].Anesthesiology,2011,115(4):754-763
[4]Zhu C,Gao J,Karlsson N,et al.Isoflurane anesthesia induced persistent,progressive memory impairment,caused a loss of neural stem cells,and reduced neurogenesis in young,but not adult,rodents[J].J Cereb Blood Flow Metab,2010,30(5):1017-1030
[5]Wang N,Lu Y,Wang K,et al.Simvastatin Attenuates Neurogenetic Damage and Improves Neurocongnitive Deficits Induced by Isoflurane in Neonatal Rats[J].Cell Physiol Biochem,2018,46(2):618-632
[6]Terushkin V,Brauer J,Bernstein L,et al.Effect of General Anesthesia on Neurodevelopmental Abnormalities in Children Undergoing Treatment of Vascular Anomalies With Laser Surgery:ARetrospective Review[J].Dermatol Surg,2017,43(4):534-540
[7]Wang H L,Ma R H,Fang H,et al.Impaired Spatial Learning Memory after Isoflurane Anesthesia or Appendectomy in Aged Mice is Associated with Microglia Activation[J].J Cell Death,2015,8(4):9-19
[8]Tachibana S,Hayase T,Osuda M,et al.Recovery of postoperative cognitive function in elderly patients after a long duration of desflurane anesthesia:a pilot study[J].J Anesth,2015,29(4):627-630
[9]Song X,Han W,He R,et al.Alterations of Hippocampal Myelin Sheath and Axon Sprouting by Status Convulsion and Regulating Lingo-1 Expression with RNA Interference in Immature and Adult Rats[J].Neurochem.Res,2018,43(3):721-735
[10]Tohda C,Naito R,Joyashiki E.Kihi-to,a herbal traditional medicine,improves Abeta(25-35)-induced memory impairment and losses of neurites and synapses[J].BMC Complement Altern Med,2008,8(1):9
[11]Gibson E M,A C Geraghty,M Monje.Bad wrap:Myelin and myelin plasticity in health and disease[J].Dev Neurobiol,2018,78(2):123-135
[12]Cai Y,Peng Z,Guo H,et al.TREK-1 pathway mediates isoflurane-induced memory impairment in middle-aged mice[J].Neurobiol Learn Mem,2017,145:199-204
[13]Zhou C H,Zhang Y H,Xue F,et al.Isoflurane exposure regulates the cell viability and BDNF expression of astrocytes via upregulation of TREK-1[J].Molecular Medicine Reports,2017,16(5):7305-7314
[14]Liu J,Wang P,Zhang X,et al.Effects of different concentration and duration time of isoflurane on acute and long-term neurocognitive function of young adult C57BL/6 mouse[J].Int J Clin Exp Pathol,2014,7(9):5828-5836
[15]Mintz C D,Barrett K M,Smith S C,et al.Anesthetics interfere with axon guidance in developing mouse neocortical neurons in vitro via a gamma-aminobutyric acid type A receptor mechanism[J].Anesthesiology,2013,118(4):825-833
[16]Hao H,Wang S.Hypothermia induced by anesthesia regulates various signals expressions in the hippocampus of animals[J].Biomed.Pharmacother,2017,95(5):1321-1330
[17]Xu J,Mathena R,Xu M,et al.Early Developmental Exposure to General Anesthetic Agents in Primary Neuron Culture Disrupts Synapse Formation via Actions on the mTOR Pathway[J].Int J Mol Sci,2018,19(8):1-16
[18]Stedehouder J,Kushner S.Myelination of parvalbumin interneurons:a parsimonious locus of pathophysiological convergence in schizophrenia[J].Mol.Psychiatry,2017,22(1):4-12
[19]Matsos A,Loomes M,Zhou I,et al.Chemotherapy-induced cognitive impairments:White matter pathologies[J].Cancer Treatment Reviews,2017,61:6-14
[20]Widder K,Tr?ger J,Kerth A,et al.Interaction of Myelin Basic Protein with Myelin-like Lipid Monolayers at Air-Water Interface[J].Langmuir,2018,34(21):6095-6108
[21]Takahashi N,Sakurai T,Davis K L,et al.Linking oligodendrocyte and myelin dysfunction to neurocircuitry abnormalities in schizophrenia[J].Prog Neurobiol,2011,93(1):13-24
[22]Kolomeets N,Uranova N.Reduced oligodendrocyte density in layer5 of the prefrontal cortex in schizophrenia[J].Eur Arch Psychiatry Clin Neurosci,2018,5[Epub ahead of print]
[23]Hamoda H,Makhlouf A,Fitzsimmons J,et al.Abnormalities in thalamo-cortical connections in patients with first-episode schizophrenia:a two-tensor tractography study[J].Brain Imaging Behav,2018,4[Epub ahead of print]
[24]Williams M,Sharma P,Macdonald C,et al.Axonal myelin decrease in the splenium in major depressive disorder[J].Eur Arch Psychiatry Clin Neurosci,2018,7[Epub ahead of print]
[25]Aston C,Jiang L,Sokolov B P.Transcriptional profiling reveals evidence for signaling and oligodendroglial abnormalities in the temporal cortex from patients with major depressive disorder[J].Mol Psychiatry,2005,10(3):309-322
[26]Banasr M,Duman R S.Glial loss in the prefrontal cortex is sufficient to induce depressive-like behaviors[J].Biol Psychiatry,2008,64(10):863-870
[27]Geurts J,B觟L,Roosendaal S,et al.Extensive hippocampal demyelination in multiple sclerosis[J].J Neuropathol Exp Neurol,2007,66(9):819-827
[28]Quintana C,Bellefqih S,Laval J,et al.Study of the localization of iron,ferritin,and hemosiderin in Alzheimer's disease hippocampus by analytical microscopy at the subcellular level[J].J Struct Biol,2006,153(1):42-54
[29]Stefanova N A,Maksimova K Y,Kiseleva E,et al.Melatonin attenuates impairments of structural hippocampal neuroplasticity in OXYS rats during active progression of Alzheimer's disease-like pathology[J].J Pineal Res,2015,59(2):163-177
[30]Brambrink A,Back S,Riddle A,et al.Isoflurane-induced apoptosis of oligodendrocytes in the neonatal primate brain[J].Ann.Neurol,2012,72(4):525-535
[31]Herrera M,Udovin L,Toro-Urrego N,et al.Palmitoylethanolamide ameliorates hippocampal damage and behavioral dysfunction after perinatal asphyxia in the immature rat brain[J].Front Neurosci,2018,12:145
[32]Steinacker P,Semler E,Anderl-Straub S,et al.Neurofilament as a blood marker for diagnosis and monitoring of primary progressive aphasias[J].Neurology,2017,88(10):961-969
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