Vacca-Galloway L L, Ikeda R, Coleman S Y
Department of Anatomy, University of Hong Kong, School of Medicine, Japan.
Cell Tissue Res. 1988 Jul;253(1):251-8. doi: 10.1007/BF00221761.
Several laboratories have reported that N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine causes damage to the nigral dopamine neurons of man, monkey, and mouse. Controversial data suggest that a rat model of Parkinsonism may be possible. Although loss of dopamine cells has not been detected in the rat brain, our immunocytochemical studies show that immunoreactive tyrosine hydroxylase, the rate-limiting enzyme which synthesizes dopamine, is significantly reduced in concentration, or its antigenicity altered, in substantia nigra/pars compacta as well as the caudate nucleus. Optical density measurements demonstrate the reduction or alteration of immunoreactive tyrosine hydroxylase in nigro-striatal neurons, indicating that axonal terminals, as well as parent perikarya, may be sensitive to the drug. After treatment, abnormal morphological remodelling may result in the affected neuronal processes, perhaps indicating sublethal toxicity, followed by slow recovery. Despite the lack of nigral cell death, it is proposed that the present data support the use of the rat as a model to investigate the early effects of Parkinsonism induced by this agent, and the biological mechanisms of cellular recovery.
几个实验室报告称，N-甲基-4-苯基-1,2,3,6-四氢吡啶会对人类、猴子和小鼠的黑质多巴胺神经元造成损害。有争议的数据表明帕金森病大鼠模型可能可行。虽然在大鼠脑中未检测到多巴胺细胞的损失，但我们的免疫细胞化学研究表明，在黑质致密部以及尾状核中，合成多巴胺的限速酶——免疫反应性酪氨酸羟化酶的浓度显著降低，或其抗原性发生改变。光密度测量显示黑质纹状体神经元中免疫反应性酪氨酸羟化酶减少或改变，表明轴突终末以及亲代核周体可能对该药物敏感。治疗后，异常的形态重塑可能导致受影响的神经元突起出现，这可能表明存在亚致死毒性，随后是缓慢恢复。尽管没有黑质细胞死亡，但有人提出，目前的数据支持将大鼠用作模型来研究该药物诱导的帕金森病的早期影响以及细胞恢复的生物学机制。
