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Effects of Brain-Derived Neurotrophic Factor (BDNF) on 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP)-induced Parkinsonism in Monkeys

脑源性神经营养因子 (BDNF) 对 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP) 诱导的猴帕金森病的影响

基本信息

批准号：
04670880
负责人：
TSUKAHARA Tetsuya
金额：
$ 1.28万
依托单位：
National cardiovascular Center, Research Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

项目摘要

The effects of intrathecal infusion of brain-derived neurotrophic factor (BDNF) were examined in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropiridine (MPTP)-induced parkinsonian model in monkeys. Nine Japanese monkeys were divided randomly into three groups : untreated control (n=3) ; BDNF group (n=3) ; and non-BDNF group(n=3). Animals in the BDNF group reccived continuous intrathecal infusion of 10 ml of cell culture medium containing a total of 10 mug of BDNF protein ; while the non-BDNF group reccived intrathecal infusion of the same culture medium not containing no BDNF.To induce Parkinsonian syndromcs, a total of 1mg/kg MPTP was administered intravenously to each monkey in both BDNF and non-BDNF groups. Neurological signs in the monkeys were monitored for 2 weeks and scored according to the monkey Parkinsonism rating scale ; histological changes in the substantia nigra were evaluated after the 2-week observation period.The BDNF-treated animals remained asymptomatic during the first week and showed mild parkinsonism during the second week, whereas the non-BDNF group showed typical Parkinsonian syndrome during the first week, with deterioration in the second week. Histological damage in the substantia nigra correlated well with the clinical features. Severe neuronal cell loss in the substantia nigra was observed in animals with severe Parkinsonism(those in the non-BDNF group), while significantly less damage was observed in this region in the BDNF group.These findings suggest that BDNF may have a preventive effect on the neurological syndrome and the histological damage of the substantia nigra in MPTP-induced Parkinsonism in monkeys.

在1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的猴帕金森模型中，研究鞘内输注脑源性神经营养因子（BDNF）的作用。9只日本猴子随机分为三组：未治疗对照组（n=3）；BDNF组，n=3；非bdnf组（n=3）。BDNF组连续鞘内输注含有10杯BDNF蛋白的细胞培养基10 ml；而非BDNF组则在鞘内输注不含BDNF的相同培养基。为了诱导帕金森综合征，在BDNF组和非BDNF组中，每只猴子静脉注射1mg/kg MPTP。监测2周后，根据猴帕金森病评定量表进行评分；观察2周后观察黑质组织学变化。bdnf治疗的动物在第一周无症状，第二周表现出轻度帕金森病，而非bdnf组在第一周表现出典型的帕金森病，第二周病情恶化。黑质组织学损伤与临床表现密切相关。在患有严重帕金森病的动物（非BDNF组）中，观察到黑质中严重的神经元细胞损失，而BDNF组在该区域观察到的损伤明显较小。这些发现提示BDNF可能对mptp诱导的帕金森猴神经系统综合征和黑质组织学损伤具有预防作用。