D-penicillamine-induced copper deficiency in suckling mice: neurological abnormalities and brain mitochondrial enzyme activities.
Brain mitochondrial enzyme activities were examined in 15-day-old suckling mice which were daily injected with D-penicillamine (DP), a chelating agent of copper. Newborn mice treated with DP (1 g/kg/day) showed retarded weight gain, hyperelasticity of skin, and a bizarre forelimb posture with subcutaneous edema on experimental day (ED) 7. Paraparesis or dragging of the hindlimbs was observed by ED 15. Brain copper contents of DP-treated mice decreased to 34% of the controls of ED 15. Cytochrome c oxidase activity (complex IV) in the brain showed 51% decrease of the controls, on the contrary, rotenone-sensitive NADH cytochrome c reductase (complex I + III) and succinate cytochrome c reductase (complex II + III) were normal. Histochemistry of cytochrome c oxidase in the cerebellum of DP-treated mice disclosed diffuse reduction of staining, especially in Purkinje cells. These data show that DP-induced copper deficiency in the brain subsequently disturbs mitochondrial electron transport system, selectively cytochrome c oxidase activity. This seems to be a useful animal model not only for Menkes' kinky hair disease but also for mitochondrial encephalomyopathy.
Yamamoto
M
M
Division of Ultrastructural Research, National Institute of Neuroscience, Tokyo, Japan.
Akiyama
C
C
Aikawa
H
H
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003300:Copper / Q000172:deficiency*; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000378:metabolism*; D006651:Histocytochemistry; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D010396:Penicillamine / Q000494:pharmacology*
D003300:Copper; D003576:Electron Transport Complex IV; D010396:Penicillamine