Persistent Regional Changes in Brain Copper, Cuproenzymes and Catecholamines Following Perinatal Copper Deficiency in Mice

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Abstract
Copper levels in the central nervous system are influenced by Cu nutriture during perinatal development. A mouse model of dietary Cu deficiency, initiated during late gestation, was employed to examine putative changes in regional levels of brain Cu, norepinephrine, dopamine and selected enzymes of 4-wk-old female and male offspring. Levels of Cu in six different regions of brain from Cu-deficient (-Cu) mice were reduced 80% or greater compared with levels in Cu-adequate (+Cu) controls. One month following Cu repletion, brain regional Cu levels were only half those measured in +Cu mice. Norepinephrine concentrations were significantly lower in all brain regions of -Cu offspring except the hypothalamus of -Cu female mice. Compared with values in +Cu mice, regional brain dopamine in -Cu mice was markedly elevated in cerebellum and medulla, unchanged in cerebrum and striatum, and elevated variably in hypothalamus and midbrain. Copper repletion normalized alterations in brain norepinephrine and dopamine concentrations. Cytochrome c oxidase activity in brain regions of -Cu mice was 29–53% of that measured in +Cu mice; the drop in midbrain was less than in other regions. Cu,Zn-superoxide dismutase activity (Cu,Zn-SOD) in brain regions of -Cu mice was 70–83% of that measured in +Cu mice. Midbrain Cu,Zn-SOD activity was not altered by Cu deficiency. Repletion of -Cu mice reversed brain regional Cu,Zn-SOD activity changes but not cytochrome c oxidase activity changes. These data extend previous observations and suggest that persistent changes to brain may occur following perinatal Cu deficiency. These data also support the hypothesis that there is brain-regional specificity in response to Cu deficiency and repletion.