Abstract
Myelination is the most important process in postnatal maturation of the nervous system and during this period the growing infant passes through a “vulnerable period” during which irreversible brain damage can occur if the neonate is subjected to a potential neurotoxin. This study was undertaken to investigate the mechanisms by which chronic hyperphenylalaninemia interferes with myelin metabolism, beyond the neonatal period of rapid myelination, at a time when myelin continues to accumulate. Rats of 25 days of age were placed on a hyperphenylalaninemia (HyPhe) inducing diet of 5 % phenylalanine plus 0.4%α-methylphenylalanine (αMP) at 25 days of age to approximate plasma phenylalanine levels of an untreated human PKU patient (1.5 mM).
The HyPhe group exhibited approximately a 15% decrease in the amount of myelin protein throughout the 70 days of the study. The rate of incorporation of 3H-lysine into both TCA precipitable whole brain proteins or myelin proteins did not vary from the HyPhe group and a weight matched control group (WMC). Therefore, this loss of myelin could not be attributed to a hypomyelination. The turnover of whole brain proteins also was unaffected by the HyPhe treatment; however, the turnover of myelin proteins in the HyPhe group was dramatically different (t1/2 = 3 days) from that of the WMC group (t1/2 = 36 days) or a group treated with only αMP (t1/2 = 26 days).