Effects of alpha-methylphenylalanine plus phenylalanine treatment during development on myelin in rat brain.
The effects of hyperphenylalaninemia induced by treatment with alpha-methylphenylalanine (MPA) plus phenylalanine (PHE) on body and brain weight, on myelin and synaptosome formation, and on the lipids and fatty acids of myelin were studied in rats. The administraton of MPA (2.4 mumol/g body wt) plus PHE (2.6 mumol/g body wt) for 25 and 35 days beginning on the fifth postnatal day did not affect brain development. On doubling the dosage of PHE, body and brain weights and myelin yields were significantly lowered. The lipid composition of myelin from the brains of treated animals was largely unaffected; however, the concentration of sulfatides ws significantly reduced. Unsaturated fatty acid levels in myelin from hyperphenylalaninemic rat brains were reduced while long-chain fatty acids were unaffected. We conclude that as in hyperphenylalaninemia induced by other methods, MPA + PHE treatment impairs body and brain growth, reduces myelin formation, and causes inhibition of fatty acid desaturation in the brain.
D000367:Age Factors; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects / Q000254:growth & development*; D009929:Organ Size; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D013433:Sulfoglycosphingolipids / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects
D005227:Fatty Acids; D013433:Sulfoglycosphingolipids; C012436:alpha-methylphenylalanine; D010649:Phenylalanine