Ma Kai-Li, Gao Jia-Hong, Huang Zhang-Qiong, Zhang Ying, Kuang De-Xuan, Jiang Qin-Fang, Han Yuan-Yuan, Li Cong, Wang Wen-Guang, Huang Xiao-Yan, Xu Juan, Tong Pin-Fen, Yin Xing-Xiao, Dai Jie-Jie
Center for Drug Safety Evaluation and Research, Institute of Medical Biology, Chinese Academy of Medical Science and Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Diseases, No. 935, Jiaoling Road, Kunming, 650118, Yunnan, China,
Neurochem Res. 2013 Jun 25. doi: 10.1007/s11064-013-1099-8.
The tree shrew, a new experimental animal model, has been used to study a variety of diseases, especially diseases of the nervous system. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is the gold standard for toxin-based animal models of Parkinson's disease (PD) because MPTP treatment replicates almost all of the pathological hallmarks of PD. Therefore, in this study, the effects of MPTP on the motor function of the tree shrew were examined. After five daily injections of a 3 mg/kg dose of MPTP, the motor function of MPTP-injected tree shrews decreased significantly, and the classic Parkinsonian symptoms of action and resting tremor, bradykinesia, posture abnormalities, and gait instability were observed in most MPTP-injected tree shrews. HPLC results also showed significantly reduced striatal dopamine and 3,4-dihydroxyphenylacetic acid levels in tree shrews after MPTP injection. Increased oxidative stress levels are usually considered to be the cause of dopaminergic neuron depletion in the presence of MPTP and were observed in the substantia nigra of MPTP-treated tree shrews, as indicated by a significant reduction in superoxide dismutase and glutathione peroxidase activity and increased levels of malondialdehyde. In addition, elevated α-synuclein mRNA levels in the midbrain of MPTP-treated tree shrews were observed. Furthermore, MPTP-treated tree shrews showed the classic Parkinsonian symptoms at a lower MPTP dosage compared with other animal models. Thus, the MPTP-treated tree shrew may be a potential animal model for studying the pathogenesis of PD.
树鼩作为一种新型实验动物模型，已被用于研究多种疾病，尤其是神经系统疾病。1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）是帕金森病（PD）基于毒素的动物模型的金标准，因为MPTP处理几乎能重现PD的所有病理特征。因此，在本研究中，检测了MPTP对树鼩运动功能的影响。每天注射3mg/kg剂量的MPTP，连续注射五天后，注射MPTP的树鼩运动功能显著下降，大多数注射MPTP的树鼩出现了典型的帕金森症状，如动作性和静止性震颤、运动迟缓、姿势异常和步态不稳。高效液相色谱结果还显示，注射MPTP后树鼩纹状体多巴胺和3,4-二羟基苯乙酸水平显著降低。氧化应激水平升高通常被认为是MPTP存在时多巴胺能神经元耗竭的原因，在MPTP处理的树鼩黑质中观察到了这种情况，表现为超氧化物歧化酶和谷胱甘肽过氧化物酶活性显著降低以及丙二醛水平升高。此外，在MPTP处理的树鼩中脑观察到α-突触核蛋白mRNA水平升高。此外，与其他动物模型相比，MPTP处理的树鼩在较低的MPTP剂量下就出现了典型的帕金森症状。因此，MPTP处理的树鼩可能是研究PD发病机制的潜在动物模型。
