Copper‐status and age alter suckling rodent brain and heart catecholamine levels

Abstract

Mice and rats were compared to determine differences in dietary copper (Cu) deficiency (Cu−) started during late gestation and/or lactation on catecholamine, norepinephrine (NE) and dopamine (DA), content in brain and heart. Limiting dopamine beta-monooxygenase (DBM) results in lower NE and higher DA in Cu− tissues compared to copper adequate (Cu+) tissues. Experiments were performed with Holtzman rats and Hsd:ICR (CD-1) outbred albino mice in which dams were fed a modified AIN-76A diet and drank deionized water or Cu supplemented water. Offspring were sampled at three time points between postnatal age 3 (P3) and P31. NE concentration increased with age in both heart and brain in Cu+ rodents. Cu− pups exhibited signs consistent with Cu deficiency, lower cuproenzyme and copper content, compared to Cu+ pups. For both rat and mouse tissue NE and DA changes were amplified at later ages in Cu− mice when Cu deficiency was limited to lactation only. Although dam Cu restriction began earlier in rats than mice, embryonic day 7 (E7) compared to E17, rat brain NE and DA alterations were not impacted as severely as mouse brain. This pattern was also true for heart NE reduction in Cu− rodents. However, Cu− mouse heart DA was impacted less than Cu− rat heart DA. Both mouse and rat models illustrate limiting DBM when dietary Cu is restricted during perinatal development. Within species, changes were more severe and proportional to the length of Cu deprivation. Both models may be useful to study the impact of Cu deficiency on altered catecholamines and their role in delayed development and altered behavior. Supported by NRI USDA CSR grant 2001-00998 and by NIH grant HD 39708.