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Oligodendrocyte development and myelinogenesis are not impaired by high concentrations of phenylalanine or its metabolites
Author(s) -
Schoemans Renaud,
Aigrot MarieStéphane,
Wu Chaohong,
Marée Raphaël,
Hong Pengyu,
Belachew Shibeshi,
Josse Claire,
Lubetzki Catherine,
Bours Vincent
Publication year - 2010
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-010-9052-3
Subject(s) - myelinogenesis , phenylalanine , hyperphenylalaninemia , phenylalanine hydroxylase , oligodendrocyte , myelin , corpus callosum , medicine , endocrinology , myelin basic protein , enzyme , biology , biochemistry , chemistry , amino acid , neuroscience , central nervous system
Phenylketonuria (PKU) is a metabolic genetic disease characterized by deficient phenylalanine hydroxylase (PAH) enzymatic activity. Brain hypomyelination has been reported in untreated patients, but its mechanism remains unclear. We therefore investigated the influence of phenylalanine (Phe), phenylpyruvate (PP), and phenylacetate (PA) on oligodendrocytes. We fisrt showed in a mouse model of PKU that the number of oligodendrocytes is not different in corpus callosum sections from adult mutants or from control brains. Then, using enriched oligodendroglial cultures, we detected no cytotoxic effect of high concentrations of Phe, PP, or PA. Finally, we analyzed the impact of Phe, PP, and PA on the myelination process in myelinating cocultures using both an in vitro index of myelination, based on activation of the myelin basic protein (MBP) promoter, and the direct quantification of myelin sheaths by both optical measurement and a bioinformatics method. None of these parameters was affected by the increased levels of Phe or its derivatives. Taken together, our data demonstrate that high levels of Phe, such as in PKU, are unlikely to directly induce brain hypomyelination, suggesting involvement of alternative mechanisms in this myelination defect.