Copper Deficiency in the Developing Rat Brain: Evidence for Abnormal Mitochondria¹

Copper deficiency was produced in developing rats by feeding a low copper diet to rats during gestation and lactation and providing the offspring the same diet. The progeny developed similar to those of an earlier model based on preconception depletion followed by marginal supplementation during gestation. Copper levels were greatly reduced in the brain, iron levels were slightly depressed, and no differences in zinc content were found. Electron microscopic examination of brain tissue revealed the presence of enlarge mitochondria from copper‐deficient animals. Isolated mitochondria from copper‐deficient rats showed a 30% reduction in the rate of both succinate and glutamate oxidation, and for glutamate, the respiratory control ratio (RCR) was decreased by 60%. Difference spectra displayed a four‐fold reduction in cytochrome a + a 3 and slight increases in cytochrome b , c 1 and c . Enzyme analysis of isolated mitochondria revealed a five‐fold decrease in cytochrome oxidase, slight increases in succinic dehydrogenase and fumarase, and small decreases in hexokinase and monoamine oxidase. No difference in peroxidation of brain lipids was evident. Determination of metabolites from fast frozen tissue suggested that the copper‐deficient brain was in a more reduced state based on a doubling of both the lactate/pyruvate and α‐glycerol‐ P /dihydroxyacetone‐ P ratios. Creatine‐ P , ATP, and ADP levels were not different.