Perinatal copper deficiency alters rat cerebellar purkinje cell size and distribution.
Copper is required for activity of several key enzymes and for optimal mammalian development, especially within the central nervous system. Copper-deficient (CuD) animals are visibly ataxic, and previous studies in rats have demonstrated impaired motor function through behavioral experiments consistent with altered cerebellar development. Perinatal copper deficiency was produced in Holtzman rat dams by restricting dietary copper during the last two thirds of gestation and lactation. Male offspring were evaluated at postnatal day 25. Compared to cerebella from copper-adequate pups, the CuD pups had larger Purkinje cell (PC) size and irregularities in the Purkinje cell monolayer. These results suggest that the ataxic behavioral phenotype of CuD rats may result from disrupted inhibitory pathways in the cerebellum. A similar PC phenotype is seen in Menkes disease and in mottled mouse mutants with genetic copper deficiency, suggesting that copper deficiency and not just specific loss of ATP7A function is responsible.
Department of Biochemistry and Molecular Biology, University of Minnesota Medical School Duluth, Duluth, MN 55812, USA.
Jacob A
JA
Lyons
Joseph R
JR
Prohaska
D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology; D048429:Cell Size; D002531:Cerebellum / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology*; D003300:Copper / Q000172:deficiency*; D004195:Disease Models, Animal; D005260:Female; D048070:Fetal Nutrition Disorders / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D005526:Food, Formulated / Q000009:adverse effects; D006801:Humans; D007228:Infant Nutrition Disorders / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007231:Infant, Newborn; D008297:Male; D055495:Neurogenesis / Q000502:physiology*; D011247:Pregnancy; D011689:Purkinje Cells / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003300:Copper