Decreased brain ascorbate levels in copper-deficient mice and in brindled mice

Mutant brindled mice, which exhibit signs of copper deficiency, were compared to their normal brothers as well as to age-matched suckling mice that were copper-deficient (-Cu) because their dams were consuming a copper-deficient diet, and a fourth group of copper-supplemented (+Cu) suckling mice, which served as dietary controls. Copper deficiency, genetic and dietary, resulted in mice with smaller brains (87 and 75%) and lower levels of the serum cuproprotein ceruloplasmin (10 and 6.1%) when compared to their respective controls. Brain ascorbic acid concentrations were determined in these mice by high performance liquid chromatography with electrochemical detection, and levels in brindled mice and -Cu mice were significantly lower (81 and 80%) than those measured in their respective controls. Injection of cupric chloride into -Cu pups raised brain ascorbate to levels found in +Cu mice and returned catecholamine levels to normal by raising norepinephrine from a major deficit (91%) and decreasing dopamine from an excess (22%). In another study, dietary copper deficiency was produced beginning at birth and continued for 7 weeks. These older -Cu mice had minor reductions in brain ascorbate (10%) and more severe reductions in norepinephrine levels (43%). Older +Cu mice had lower ascorbate and higher norepinephrine levels compared to suckling control mice.(ABSTRACT TRUNCATED AT 250 WORDS)