Nagashima K
Department of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
Toxicol Pathol. 1997 Nov-Dec;25(6):624-31. doi: 10.1177/019262339702500613.
As an animal model for examining the pathogenicity of human organic mercury intoxication, rats have been used for the reproduction of human neurologic diseases. Rats experimentally exposed to methylmercury chloride showed clinical signs of neurologic dysfunction characterized by ataxic behavior. Neuropathology of the diseased animals consisted of lesions such as: (a) degeneration of the peripheral nerve and sensory root nerve with preservation of the motor root nerve; (b) degeneration of the posterior funiculus of the spinal cord; and (c) degeneration of cerebellar granule cells with preservation of Purkinje cells. These findings suggest the human neuropathology of this toxicity. The degeneration was characterized by nerve fiber damage or neuronal cell death accompanied by astrocytic gliosis and activated macrophages or microglias. For the cerebellar granule cells, the mechanism of neuronal cell death was shown to be apoptosis. This fact was verified by histologic and ultrastructural findings as well as by in situ nick-end labeling and electrophoretic methods. Evidence of apoptosis involvement in cerebellar degeneration would provide a new viewpoint from which to analyze the selected degeneration of the nervous system in neurotoxicology.
作为研究人类有机汞中毒致病性的动物模型，大鼠已被用于重现人类神经疾病。实验性暴露于氯化甲基汞的大鼠表现出以共济失调行为为特征的神经功能障碍临床症状。患病动物的神经病理学表现为以下病变：(a) 周围神经和感觉神经根神经变性，运动神经根神经保留；(b) 脊髓后索变性；(c) 小脑颗粒细胞变性，浦肯野细胞保留。这些发现提示了这种毒性的人类神经病理学特征。这种变性的特点是神经纤维损伤或神经元细胞死亡，伴有星形胶质细胞增生和活化的巨噬细胞或小胶质细胞。对于小脑颗粒细胞，神经元细胞死亡的机制被证明是凋亡。这一事实通过组织学和超微结构发现以及原位缺口末端标记和电泳方法得到了证实。凋亡参与小脑变性的证据将为分析神经毒理学中神经系统的特定变性提供一个新的视角。
