Protective action of recombinant neurturin on dopaminergic neurons in substantia nigra in a Rhesus monkey model of Parkinson's disease
Protective action of recombinant neurturin on dopaminergic neurons in substantia nigra in a Rhesus monkey model of Parkinson's disease
复制标题
重组neurturin对帕金森病恒河猴模型黑质多巴胺能神经元的保护作用
作者：
Hongjun Li;Zhanlong He;Ting Su;Yanbing Ma;Shuaiyao Lu;C. Dai;Mao
帕金森病（Parkinson 'sDisease，PD）是一种神经退行性疾病，其主要特征是黑质-纹状体系统多巴胺（Dopamine，DA）缺乏，导致多巴胺能神经元变性、坏死，导致肌肉震颤麻痹。Neurturin（NTN）是一种特异性作用于中脑多巴胺能神经元的神经保护剂。本研究采用1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）诱发恒河猴帕金森病模型。将恒河猴随机分为PD模型组、NTN治疗组和正常对照组。NTN治疗组给予E.在注射MPTP前48 h，将来源于大肠杆菌的重组人NTN注入脑室。结果表明，PD模型组的恒河猴获得了PD症状，并随着时间的推移而逐渐加重，而NTN治疗组的猴子则不太明显或没有症状。用荧光分光光度法测定了模型组猴黑质、壳核和尾状核内多巴胺（DA）、5-羟色胺（5-HT）和5-羟吲哚乙酸（5-HIAA）含量，结果表明，模型组猴黑质、壳核和尾状核内DA、5-HT和5-HIAA含量均显著低于正常对照组。NTN治疗组DA、5-HT和5-HIAA含量均高于PD模型组，与正常对照组比较差异无显著性。光镜下观察到PD模型组猴黑质神经元数量明显减少，而NTN治疗组未见明显减少，神经元数量与正常对照组相似。这些结果表明，重组人NTN可以预防PD症状，以及保护多巴胺能神经元和保护DA含量在中脑黑质暴露于MPTP的恒河猴。
Abstract Parkinson's disease (PD) is a neurodegenerative disease characterized by muscular trembling palsy due to lack of dopamine (DA) in the substantia nigra-striatum (nigrostriatal) system resulting from the degeneration and necrosis of dopaminergic neurons. No effective cure has been found. Neurturin (NTN) has been demonstrated to act specifically on midbrain (mesencephalic) dopaminergic neurons with protective actions specifically. In the present study, we induced rhesus monkey model of Parkinson's disease by injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Rhesus monkeys were randomly divided into a PD model group, NTN treatment group and normal control groups. In the NTN treatment group, 1 mg of E. coli- derived recombinant human NTN was injected into the cerebral ventricles 48 h before the injection of MPTP. Results indicated that Rhesus monkeys in the PD model group acquired PD symptoms that increasingly aggravated over time, while monkeys treated with NTN had less apparent or no symptoms. Using fluorospectrophotometry, the dopamine (DA), 5, 5-hydroxytrytamine (5-HT) and the 5-hydroxyindoleacetic acid (5-HIAA) contents of DA, 5-HT and 5-HIAA in substantia nigra, putamen and caudate nucleus in monkeys from the model group was found to be significantly lower than in the normal control group. While no significant differences were found between monkeys treated with NTN and normal control groups, the contents of DA, 5-HT and 5-HIAA in the NTN treatment group were higher than those observed in the PD model group. A dramatic loss of neurons in the substantia nigra in monkeys in the PD model group was observed by light microscopy, while no obvious loss was observed in the NTN treatment group in which the numbers of neurons were similar to those in normal controls. These results indicate that recombinant human NTN can prevent PD symptoms as well as protect dopaminergic neurons and preserve DA content in midbrain substantia nigra in rhesus monkeys exposed to MPTP.
影响因子：
56.9
作者：
BARR, E;LEIDEN, JM
通讯作者：
LEIDEN, JM