PERSISTENT NEUROCHEMICAL CHANGES FOLLOWING PERINATAL COPPER DEFICIENCY IN RATS

Copper (Cu) levels in the central nervous system are known to be influenced by Cu nutriture during perinatal development. A rat model of dietary Cu deficiency (-Cu), initiated during gestation, was employed to examine changes in regional levels of brain Cu, norepinephrine (NE), dopamine (DA) and selected enzymes of month-old female Sprague Dawley offspring. Nutritional repletion of Cu to -Cu rats was studied following 1, 2, or 4 months. Levels of Cu in six different regions of brain from -Cu rats were reduced 80% or greater compared with levels in Cu-adequate (+Cu) controls. Following 4 months of Cu repletion, brain regional Cu levels were still below those measured in +Cu rats. The norepinephrine/dopamine was higher in +Cu compared with -Cu rats for all brain regions except corpus striatum suggesting impairment of dopamine-beta-monooxygenase (DBM). Cu repletion normalized these ratios after 1 month. In vitro DBM activity was higher in samples from -Cu compared with +Cu rats and,these differences were reversed by Cu supplementation. Cytochrome c oxidase (CCO) activity of 1-month-old -Cu rats was 18 to 50% of that measured in +Cu rats. Small differences in CCO activity remained in all regions, except hypothalamus, even after 4 months of repletion. Cu,Zn-superoxide dismutase activity (Cu,Zn-SOD) in -Cu rats was 75 to 91% of that measured in +Cu rats and was equivalent following repletion for 1 month. Four months of Cu repletion were not sufficient to restore brain Cu and CCO levels of I-month-old -Cu rats.