title: Reduced myelinogenesis and recovery in hyperphenylalaninemic rats. Correlation between brain phenylalanine levels, characteristic brain enzymes for myelination, and brain development.
abstract: In a previous paper (Burri et al., 1990), we have shown that experimental hyperphenylalaninemia (hyper-Phe) in 3-17 d-old rats leads to reduced myelinogenesis. Such treated rats recover during a 6 w low phenylalanine (Phe) period between days 17 and 59. In order to get more detailed information about the disturbed myelinogenesis and recovery, we measured in hyper-Phe rats the developmental pattern of two brain enzymes typical for myelination, cerebroside sulfotransferase (CST), and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP), and other developmental parameters. Further, we correlated brain Phe levels with the brain damage in hyper-Phe rats, and we measured brain acetylcholinesterase (AChE) as a neuronal marker. Experimental hyper-Phe rats, injected between postnatal days 3 and 17 with alpha-methylphenylalanine and phenylalanine, showed a delayed age-dependent increase of CST activity, compared to that of controls. In hyper-Phe rats, CST peak activity was reached 2-4 d later, and was lower than in controls. The age-dependent decrease of the CST activity, however, started in test and control rats at the same time, at day 21. Between days 24 and 59, hyper-Phe rats had normal CST activity. CNP activity in hyper-Phe rats was lower than in controls from day 10 to 35, and recovered to normal values between days 35 and 59. Our results indicate that recovery from reduced myelinogenesis is possible after the period of fast myelination without compensatory increased CST activity. Further, the brain damage in test rats with Phe levels higher than average is more severe than in test rats with Phe levels lower than average; and there is no effect of hyperphenylalaninemia on brain neurons containing AChE.
authors.affiliation: University of Berne, Department of Pediatrics, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Burri
authors.forename: C
authors.initials: C
authors.lastname: Steffen
authors.forename: S
authors.initials: S
authors.lastname: Stieger
authors.forename: U
authors.initials: U
authors.lastname: Brodbeck
authors.forename: J P
authors.initials: JP
authors.lastname: Colombo
authors.forename: N
authors.initials: N
authors.lastname: Herschkowitz
mesh_terms: D000110:Acetylcholinesterase / Q000032:analysis; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000254:growth & development; D001923:Brain Chemistry; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D009186:Myelin Sheath / Q000502:physiology*; D009474:Neurons / Q000201:enzymology; D010649:Phenylalanine / Q000097:blood*; D010661:Phenylketonurias / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D010649:Phenylalanine; D000110:Acetylcholinesterase