Gender influences the effect of perinatal copper deficiency on cerebellar PKC gamma content

Change in cerebellar protein kinase C gamma (PKCgamma) content caused by perinatal copper (Cu) deficiency was determined in 22-day old rats. The offspring of dams with low Cu intake during gestation and lactation exhibited signs characteristic of Cu deficiency including anemia, greater than 90% reduction in liver Cu concentration, and undetectable serum ceruloplasmin. In addition, brain Cu concentrations were reduced 80%. No differences in the signs of Cu deficiency were observed between female and male offspring. However, cerebellar PKCgamma content was reduced 54% (P < 0.05, Tukey's test) in female offspring but only 18% (P > 0.05) in male offspring. Following 6 weeks of Cu supplementation, brain Cu concentrations remained depressed in female and male rats that experienced perinatal Cu deficiency, but cerebellar PKCgamma content was completely restored to control levels. Postnatal expression of PKCgamma in the cerebellum coincides with and regulates cerebellar maturation. The results of the present study indicate perinatal Cu deficiency may impair cerebellar maturation to a greater extent in females than in males. However, it is not clear whether suppression of PKCgamma by perinatal Cu deficiency produces permanent neuropathology in the cerebellum because the effects were reversed by Cu supplementation.