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)诱导的猴帕金森病模型上，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)、脑源性神经营养因子组(n=3)和非脑源性神经营养因子组(n=3)。脑源性神经营养因子组大鼠鞘内持续输注10ml细胞培养液，细胞培养液中含BDNF蛋白10µg，非脑源性神经营养因子组大鼠鞘内输注不含脑源性神经营养因子的培养液，每只猴静脉注射MPTP 1 mg/kg。观察2周后观察神经体征，根据帕金森病评定量表进行评分，观察2周后黑质组织学变化，BDNF治疗组动物1周无症状，2周出现轻度帕金森病，而非BDNF组1周出现典型的帕金森综合征，2周后病情加重。黑质的组织学损害与临床特征密切相关。重度帕金森病动物(非BDNF组)黑质神经元严重丢失，而BDNF组黑质神经元损伤明显减轻，提示BDNF可能对MPTP诱导的帕金森病猴的神经症状和黑质组织学损伤有预防作用。

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.