Differential effects of hyperphenylalaninemia on the development of the brain in the rat

Abstract

Rats made hyperphenylalaninemic from 13 to 21 days of age by subcutaneous injections of 4 mg/g of l-phenylalanine/day exhibit a 12% reduction in brain weight and a 20.5% reduction in cerebellar weight when compared to control siblings. There was a 29.7% decrease in the DNA content of the cerebellums of the hyperphenylalaninemic animals; the RNA-DNA ratio was slightly elevated when compared to controls but the protein-DNA ratio remained constant. The cerebral hemispheres were examined in 5 severely affected animals and 5 control siblings. The DNA content of the hemispheres was similar in the hyperphenylalaninemic and control groups. In the hyperphenylalaninemic group there was a marked reduction in the cerebral RNA-DNA and protein-DNA ratios, and lipid synthesis was severely curtailed (65.2% of control values). The reduction was most marked in the formation of galactolipids (41.8% of controls) and proteolipid proteins (50.0% of controls), suggesting that the formation of myelin can be significantly reduced in the cerebrum without a decrease in DNA. However, the chemical composition of the myelin membrane isolated from hyperphenylalaninemic animals closely resembles that of controls at 21 days of age. It is suggested that those synthetic processes which take place at the most rapid rate during the experimental period are most vulnerable to the insult.