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

在1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）诱发的猴帕金森病模型中，观察了鞘内注射脑源性神经营养因子（BDNF）的作用。将9只日本猕猴随机分为3组：未处理对照组（n=3）、BDNF组（n=3）和非BDNF组（n=3）。BDNF组的动物接受连续鞘内输注10 ml含有总共10 μ g BDNF蛋白的细胞培养基，而非BDNF组接受鞘内输注不含BDNF的相同培养基。为了诱导帕金森综合征，在BDNF组和非BDNF组中每只猴子静脉内给予总共1 mg/kg MPTP。监测猴的神经系统体征2周，并根据猴帕金森病评定量表进行评分; BDNF治疗的动物在第一周期间保持无症状，在第二周期间显示轻度帕金森综合征，而非BDNF组在第一周期间显示典型的帕金森综合征，在第二周恶化。黑质的组织学损害与临床特征相关。在重度帕金森病动物（非BDNF组）中观察到黑质神经元细胞严重丢失，而在BDNF组中观察到该区域的损伤明显减轻。这些结果表明BDNF可能对MPTP诱导的帕金森病猴的神经系统综合征和黑质组织学损伤具有预防作用。

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.