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MPTP对快速老化小鼠SAMP8学习记忆能力及黑质多巴胺神经元的影响
苑振云1,2,顾平2,3,籍文强1,崔冬生2,刘力2,王彦永2,3,耿媛2,王铭维2,3*
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(1.河北医科大学第一医院急诊科,石家庄050031;2.河北省脑老化与认知神经科学实验室,石家庄050031 ; 3.河北医科大学第一医院神经内科,石家庄050031)
摘要:
目的:探讨1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)对SAMP8小鼠空间学习和记忆能力及黑质多巴胺神经元的影响。方法:采用雄性3个月龄 SAMP8小鼠皮下注射MPTP(36 mg/kg),连续5 d。对照组皮下注射生理盐水(NS,36 ml/kg)。用Morris水迷宫测试小鼠的寻找平台潜伏期及搜索策略。免疫组织化学观察黑质酪氨酸羟化酶(TH)阳性多巴胺能神经元变化。结果:MPTP小鼠黑质致密部TH免疫反应阳性神经元数目明显少于对照组(P<0.01)。 Morris水迷宫实验表明MPTP小鼠寻找平台潜伏期较对照组明显延长(P<0.01),在目标象限(第Ⅰ象限)游泳时间比对照组明显降低(P<0.01),在对侧象限(第Ⅳ象限) 游泳时间比对照组明显升高(P<0.05),搜寻策略较对照组变差。 结论:MPTP可造成SAMP8小鼠黑质多巴胺神经元损伤,并出现空间学习记忆能力下降。
关键词:  MPTP  SAMP8  多巴胺能神经元  学习  记忆
DOI:10.3724/SP.J.1008.2008.01337
投稿时间:2008-05-15修订日期:2008-10-13
基金项目:
Effects of MPTP on spatial learning ability/memory and dopaminergic neurons in Nigra of senescence accelerated-prone 8 mice
YUAN Zhen-yun1,2,GU Ping2,3,JI Wen-qiang1,CUI Dong-sheng2 ,LIU Li2,WANG Yan-yong2,3,GENG Yuan2,WANG Ming-wei2,3*
(1.Department of Emergency,First Hospital of Hebei Medical University,Shijiazhuang 050031,China;2.Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province,Shijiazhuang 050031;3.Department of Neurology,First Hospital of Hebei Medical University,Shijiazhuang 050031)
Abstract:
Objective:To observe the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the spatial learning ability/memory and dopaminergic neurons in the Nigra of senescence accelerated-prone 8 (SAMP8) mice.Methods: Three-month old male SAMP8 mice were injected with MPTP (36 mg/kg,s.c.) for 5 days,and animals in the control group were injected with NS (36 ml/kg,s.c.) in the same manner.Morris water maze was used to examine the searching strategy,seeking-platform latency,and the swimming time in the aimed quadrant.Immunohistochernistry was used to observe the changes of TH-ir positive neurons in substantia nigra.Results: The number of TH-ir neurons in substantia nigra pars compacta was significantly reduced in MPTP group compared with the control group(P<0.01).Morris water maze showed that the searching strategy of animals in MPTP group was worse than in the control group,with the seeking-platform latency of MPTP mice significantly prolonged (P<0.01),the time spent in the aimed quadrant significantly decreased (P<0.01) and time in the opposite quadrant significantly prolonged (P<0.05).Conclusion: MPTP can cause damage to the dopaminergic neurons in the substantia nigra of SAMP8 mice,which is subsequently followed by deficit in the spatial learning and memory in the animals.
Key words:  MPTP  SAMP8  dopaminergic neuron  learning  memory