Effects of protein energy malnutrition on rat brain: Studies on free amino acids, serotonin and norepinephrine.

The effects of protein-energy malnutrition on the concentrations of free amino acids, serotonin and norepinephrine in the brains of rats have been studied. The concentrations of glutamic acid, aspartic acid, GABA, glutamine and serotonin have been measured in the forebrain, cerebellum and brainstem of the rat between 7 and 120 days of age. DNA content was studied as a measure of cell number. Maternal protein deficiency from the 5th day of gestation did not result in any significant changes in the concentrations of glutamic acid, aspartic acid, GABA, serotonin and norepinephrine in the whole brain of one day old rats. Pre- and post-natal maternal protein deficiency, on the other hand, resulted in an increase in the concentration of aspartic acid and a decrease in that of glutamic acid in the forebrain, and an increase in the concentration of aspartic acid and in that of GABA in the cerebellum of offspring at 21 d of age. The activity of the enzyme glutamic acid decarboxylase was higher in the cerebellum of the malnourished rats at this age. The entry of U-C[14]-D-glucose was depressed in the forebrain and cerebellum in these animals. The free amino acid concentration in the brain returned to normal after rehabilitation for 120 d whereas the DNA content and cholesterol concentration did not. In male weanling rats fed a low protein diet for 56 days, the composition of the free amino acid was changed. There were differences between the different parts of the brain but the concentration of histidine and methionine were increased in each part studied. In rats fed a high protein diet of equal energy content, the free amino acid pool in the three brain parts was also altered, but not in the same way as in the animals that had eaten the low protein diet. The in vivo uptakes of C[14]-methionine and H[3]-histidine were increased. The incorporation of C[14]-methionine into brain protein was also increased. Giving a low protein diet to weanling rats also depressed the serotonin concentration in the forebrain and brainstem. The in vivo uptake of H[3]-tryptophan into the brain and its incorporation into brain protein was depressed in rats on a low protein diet, but not in those on a restricted high protein diet. Insulin injection enhanced the uptake of H[3]-tryptophan and its incorporation into brain protein in low protein animals. The possible relevance of this work to brain function and to the malnourished child is discussed