Brain Development in Experimental Hyperphenylalaninaemia: Myelination

Abstract

The influence of hyperphenylalaninaemia on the formation and composition of myelin has been investigated in forebrain and spinal cord of young rats (10-60 days p.p.). The injection of α-methylphenylalanine plus phenylalanine in 12 hour intervals (from 3rd day post partum) resulted in decreased wet weights of brain and spinal cord and reduced myelin yields; both were more pronounced in the forebrain. Myelination was initially delayed in the forebrain but thereafter the rate of myelination was the same in both control and hyperphenylalaninaemic rats. Transient alterations of several parameters of myelination were observed during early stages of development. Myelin isolated from the CNS of hyperphenylalaninaemic rats at 10 and 20 days p.p. was slightly more mature with respect to sedimentation characteristics, protein pattern, fatty acid composition of certain myelin lipids, and electron microscopic structure of myelin preparations. No significant changes in the myelin composition of the preparations of both forebrain and spinal cord were found at later developmental stages (30 and 60 days p.p.). The findings are discussed in relation to alterations in the axonal outgrowth rather than to a specific effect of hyperphenylalaninaemia on myelin formation.

Key words

Phenylketonuria - Hyperphenylalaninaemia - Myelin - Brain development