title: Effect of experimental hyperphenylalaninemia on myelin metabolism at later stages of brain development.
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 hyperphenylalanimenia (HyPhe) inducing diet of 5% phenylalanine plus 0.4% alpha-methylphenylalanine (alpha MP) 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 hypo-myelination. 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 (t 1/2 = 3 days) from that of the WMC group (t 1/2 = 36 days) or a group treated with only alpha MP (t 1/2 = 26 days).
mesh_terms: D000596:Amino Acids / Q000097:blood; D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000378:metabolism; D005260:Female; D006801:Humans; D009185:Myelin Proteins / Q000378:metabolism*; D009413:Nerve Fibers, Myelinated / Q000378:metabolism; D010649:Phenylalanine / Q000097:blood*; D010661:Phenylketonurias / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000596:Amino Acids; D009185:Myelin Proteins; D010649:Phenylalanine