Neurochemical and histochemical evidence for an abnormal catecholamine metabolism in the cerebral cortex of the Long-Evans Cinnamon rat before excessive copper accumulation in the brain.
Distributions of norepinephrine (NE), dopamine (DA) and its metabolites in the cerebral cortex in Long-Evans Cinnamon (LEC) rats, an animal model of Wilson's disease, aged 4, 10 (in the early stage of the disease) and 20 weeks (in the advanced stage of the disease) were determined to elucidate the effect of the abnormal copper (Cu) metabolism observed in the LEC rat on the brain catecholamine metabolism. NE depression as well as excessive accumulations of DA and facilitation of the DA catabolic pathway to its acidic metabolites were observed in the cerebral cortex of the LEC rat at 4 and 10 weeks of age. Furthermore, immunohistochemical analysis of the cuproenzyme dopamine-beta-hydroxylase (DBH) showed lower antigenicity of DBH in the cortical neurons in the cerebral cortex of LEC rats aged 4 weeks than in control rats. These results suggest that neurochemical disturbances involved in an abnormal catecholamine metabolism may occur in the cerebral cortex of the LEC rat before excessive Cu accumulation.
Department of Hygiene and Preventive Medicine, Hokkaido University School of Medicine, Sapporo, Japan. taksaito@med.hokudai.ac.jp
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D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D003300:Copper / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006527:Hepatolenticular Degeneration / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011922:Rats, Mutant Strains
D015102:3,4-Dihydroxyphenylacetic Acid; D003300:Copper; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid