Effect of dietary or genetic copper deficiency on brain catecholamines, trace metals and enzymes in mice and rats.
Previous studies by others indicated that alterations in brain catecholamines were different for perinatal copper deficiency produced by diet in rats and that resulting from a genetic mutation of the X-chromosome, Menkes' syndrome in humans and brindled mice. Thus, copper deficiency was studied in a model in which dietary and genetic deficiency (brindled mice) were compared in two strains of the same species. C57BL and C3H/HeJ mice. Dietary copper deficiency was also produced in rats for comparison. In brain, both dietary and genetic copper deficiency resulted in impaired growth, low brain copper levels, greatly decreased norepinephrine concentrations but normal dopamine levels. The activity of brain cytochrome oxidase was greatly depressed following both dietary and genetic copper deficiency, suggesting a functional deficit of copper. However, the activity of another cuproenzyme, dopamine-beta-hydroxylase, was significantly elevated in deficient animals. The elevation was observed when either copper or N-ethylmaleimide was added to inactivate an endogenous inhibitor. The cause of low brain norepinephrine remains unknown; however, depressed brain norepinephrine may be partly responsible for functional changes in the deficient animals, such as hypomyelination, since the activity of the myelin protein, 2',3'-cyclic nucleotide 3'-phosphodiesterase, was lower in the most deficient animals.
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001928:Brain Diseases, Metabolic / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D003300:Copper / Q000172:deficiency* / Q000378:metabolism; D004195:Disease Models, Animal; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism; D008297:Male; D007706:Menkes Kinky Hair Syndrome / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D011919:Rats, Inbred Strains; D014131:Trace Elements / Q000378:metabolism*
D002395:Catecholamines; D014131:Trace Elements; D003300:Copper; D007501:Iron; D005979:Glutathione Peroxidase; D004299:Dopamine beta-Hydroxylase; D003576:Electron Transport Complex IV; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases