Copper deficiency alters the neurochemical profile of developing rat brain.
Copper deficiency is associated with impaired brain development and mitochondrial dysfunction. Perinatal copper deficiency was produced in Holtzman rats. In vivo proton NMR spectroscopy was used to quantify 18 cerebellar and hippocampal metabolites on postnatal day 21 (P21). Copper status was evaluated in male copper-adequate (CuA) and copper-deficient (CuD) brothers at P19 and at P23, 2 days following NMR experiments, by metal and in vitro metabolite data. Compared to CuA pups, CuD pups had lower ascorbate concentration in both brain regions, confirming prior HPLC data. Both regions of CuD rats also had lower N-acetylaspartate levels consistent with delayed development or impaired mitochondrial function similar to prior work demonstrating elevated lactate and citrate. For other metabolites, the P21 neurochemical profile of CuD rats was remarkably similar to CuA rats but uniquely different from iron-deficient or chronic hypoxia models. Further research is needed to determine the neurochemical consequences of copper deficiency.
Department of Biochemistry and Molecular Biology, University of Minnesota Medical School, Duluth, Minnesota 55812, USA.
Anna A
AA
Gybina
Ivan
I
Tkac
Joseph R
JR
Prohaska
D000375:Aging; D000818:Animals; D001205:Ascorbic Acid / Q000032:analysis; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000032:analysis; D001921:Brain / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D001923:Brain Chemistry; D002531:Cerebellum / Q000737:chemistry; D019343:Citric Acid / Q000032:analysis; D003300:Copper / Q000032:analysis / Q000172:deficiency*; D003401:Creatine / Q000032:analysis; D005260:Female; D006624:Hippocampus / Q000737:chemistry; D019344:Lactic Acid / Q000032:analysis; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008928:Mitochondria / Q000502:physiology; D010725:Phosphocreatine / Q000032:analysis; D051381:Rats
D010725:Phosphocreatine; D019343:Citric Acid; D001224:Aspartic Acid; D019344:Lactic Acid; D003300:Copper; C000179:N-acetylaspartate; D003401:Creatine; D001205:Ascorbic Acid