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丰富环境对MPTP致快速老化小鼠脑损伤的干预效应
苑振云,王铭维*,顾平,崔冬生,王彦永,耿媛
0
(河北医科大学第一医院,河北省脑老化与认知神经科学实验室,石家庄 050031)
摘要:
[摘要]目的观察丰富环境(EE)对快速老化(SAMP8)小鼠黑质脑源性神经营养因子(BDNF)的影响,探讨EE保护黑质多巴胺神经元降低1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)损伤的机制。 方法80只3个月龄雌性SAMP8小鼠随机分为EE组和标准环境组(SE组)。饲养3个月后,EE组和SE组小鼠分别随机分为MPTP组和生理盐水对照组(NS组),每组20只。 MPTP组小鼠皮下注射MPTP(14 mg/kg每2 h一次,共4次),NS组小鼠皮下注射等量的生理盐水。第7天取鼠脑采用RT-PCR方法观测黑质BDNF mRNA,免疫组织化学方法观察黑质BDNF 免疫反应性的表达。 结果EE+NS组与SE+NS组比较,黑质BDNF mRNA表达增加(P<0.01);黑质区BDNF-ir阳性细胞数及矫正光密度(COD)值均增加(P<0.01)。SE+MPTP组与SE+NS组比较,黑质 BDNF mRNA表达下降(P<0.001);黑质区BDNF-ir阳性细胞数及COD值均下降(P<0.01)。EE+MPTP组与SE+MPTP组比较,黑质BDNF mRNA表达增加(P<0.01);黑质区BDNF-ir阳性细胞数及COD值均增加(P<0.01)。结论EE能增加SAMP8小鼠黑质区BDNF mRNA及BDNF-ir的阳性表达,降低MPTP对SAMP8小鼠黑质的损伤,对黑质有保护作用。
关键词:  丰富环境  1-甲基-4-苯基-1,2,3,6-四氢吡啶  快速老化小鼠  神经营养因子
DOI:10.3724/SP.J.1008.2010.01179
投稿时间:2010-06-29修订日期:2010-09-03
基金项目:河北省自然科学基金(C2009001242),河北省卫生厅课题(20090338).
Intervention effects of enriched environment on brain damage of MPTP-induced senescence-accelerated prone mice
YUAN Zhen-yun, WANG Ming-wei*, GU Ping, CUI Dong-sheng, WANG Yan-yong, GENG Yuan
(First Hospital of Hebei Medical University, Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province, Shijiazhuang 050031, Hebei, China)
Abstract:
[Abstract]ObjectiveTo observe the effects of enriched environmen(EE) on brain-derived neurotrophic factor (BDNF) in substantia nigra (SN) of senescence-accelerated prone mice, so as to explore the possible mechanism of EE in alleviating MPTP-induced damage and in protecting dopaminergic neurons in the SN. MethodsTotally 80 3-month old female SAMP8 mice were averagely assigned to EE and standard environment (SE) groups at random. After three months, the mice in each group were further divided into 2 subgroups at random: MPTP group and NS group (n=20). The MPTP groups received subcutaneous injection of MPTP, and the NS mice were treated with an equal volume of NS. At the seventh day, the mice were sacrificed for RT-PCR and immunohistochemistry staining. RT-PCR was used to examine BDNF mRNA expression and immunohistochemistry staining was used to examine BDNF-ir expression. MethodsCompared with SE+NS mice, EE+NS mice had significantly increased BDNF mRNA expression(P<0.01), and the number of BDNF-ir cell and COD values in SN were also significantly increased (P<0.01). Compared with SE+NS mice, SE+MPTP mice showed significantly decreased BDNF mRNA expression (P<0.001), and the number of BDNF-ir cells and the COD values in SN of mice were significantly decreased (P<0.01). Compared with SE+MPTP mice, EE+MPTP mice showed increased BDNF mRNA expression (P<0.01), and the number of BDNF-ir cells and the COD values in SN were significantly increased (P<0.01).MethodsEE can increase BDNF mRNA expression and BDNF-ir cell number in SN of SAMP8 mice, alleviating MPTP-induced SN damage.
Key words:  enriched environment  1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine  senescence accelerated mouse  neurotrophic factor