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Decreased Brain Ascorbate Levels in Copper-Deficient Mice and in Brindled Mice¹

Department of Biochemistry, School of Medicine, University of Minnesota, Duluth, Duluth, MN 55812

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 more severe reductions in norepinephrine levels (43%). Older + Cu mice had lower ascorbate and higher norepinephrine levels compared to suckling control mice. Normal adult male mice, injected with diethyldithiocarbamate, an inhibitor of dopamine-ß-monooxygenase, had significant reductions in norepinephrine (40%), while ascorbate was significantly elevated (8%). These results indicate a novel interaction between copper and vitamin C. Copper deficiency in brain is associated with lower tissue ascorbate levels. This reduction, however, may not be responsible for the depression in norepinephrine levels.

KEY WORDS: • copper deficiency • brindled mice • ascorbic acid • HPLC with electrochemical detection • norepinephrine

¹ This research was supported by U.S. Public Health Service grant HD-15491.

Manuscript received 27 June 1983.