A review of experimental methylmercury toxicity in rats: neuropathology and evidence for apoptosis.
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.
Nagashima
K
K
Department of Pathology, Hokkaido University School of Medicine, Sapporo, Japan. knagasi@med.hokudai.ac.jp
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001933:Brain Stem / Q000187:drug effects / Q000473:pathology; D002531:Cerebellum / Q000187:drug effects / Q000473:pathology; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D017950:Ganglia, Sensory / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008630:Mercury Poisoning / Q000473:pathology*; D008767:Methylmercury Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D017933:Peripheral Nervous System / Q000187:drug effects / Q000473:pathology; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology
D008767:Methylmercury Compounds; D004247:DNA