Experimental hyperphenylalaninemia: Effect on central nervous system myelin subfractions

Abstract

We examined the effects of experimental hyperphenylalaninemia on the formation of subfractions of myelin in the central nervous system of 18- to 110-day-old rats. Hyperphenylalaninemia was induced by giving rats daily subcutaneous injections of α-methylphenylalanine and phenylalanine from the 3rd to the 15th postnatal day. A mixture of [ 3H]glycine and [ 14C]glucose was injected intraventricularly into 17-, 20-, and 24-day-old control and experimental rats 18 h prior to the isolation and subfractionation of CNS myelin. Nonradioactive myelin subfractions were isolated from 43- and 110-day-old rats. Animals that had been hyperphenylalaninemic between the 3rd and 15th postnatal day exhibited a deficiency of total myelin protein throughout the study. With the exception of one age, these rats had a deficit of the classical, mature light myelin. The light and medium myelin subfractions from 18- to 43-day-old experimental rats and heavy myelin from the 25- and 43-day-old experimental rats had a deficiency of myelin basic proteins and an excess of the high molecular weight proteins. Nonetheless, previously hyperphenylalaninemic rats incorporated more [ 3H]glycine into the basic proteins of all myelin subfractions. The proportion of total brain [ 3H] glycine and [ 14C]glucose that was incorporated into combined (total) myelin subfractions was near normal in rats that were hyperphenylalaninemic between the 3rd and 15th postnatal day. However, these rats demonstrated decreased 3H and 14C incorporation into light myelin at 21 and 25 days, increased 3H and 14C incorporation into medium myelin at 25 days, and increased incorporation into heavy myelin at 21 days.