Reference : Oligodendrocyte development and myelinogenesis are not impaired by high concentration...
Scientific journals : Article
Human health sciences : Neurology
Oligodendrocyte development and myelinogenesis are not impaired by high concentrations of phenylalanine or its metabolites.
Schoemans, Renaud [> > > >]
Aigrot, Marie-Stephane [> > > >]
Wu, Chaohong [> > > >]
Marée, Raphaël [Université de Liège - ULiège > > GIGA-Management : Plateforme bioinformatique >]
Hong, Pengyu [> > > >]
Belachew, Shibeshih mailto [Université de Liège - ULiège > Département des sciences cliniques > Neurologie >]
Josse, Claire [Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique générale et humaine >]
Lubetzki, Catherine [> > > >]
Bours, Vincent [Centre Hospitalier Universitaire de Liège - CHU > > Génétique >]
Journal of Inherited Metabolic Disease
Kluwer Academic Publishers
Yes (verified by ORBi)
The Netherlands
[en] Animals ; Cells, Cultured ; Corpus Callosum/metabolism/pathology ; Disease Models, Animal ; Lac Operon ; Mice ; Mice, Mutant Strains ; Mice, Transgenic ; Myelin Basic Proteins/genetics/metabolism ; Myelin Sheath/metabolism/pathology ; Oligodendroglia/cytology/drug effects/metabolism ; Phenylalanine/metabolism/pharmacology ; Phenylalanine Hydroxylase/genetics/metabolism ; Phenylketonurias/metabolism/pathology/physiopathology ; Promoter Regions, Genetic/physiology ; Rats ; Rats, Wistar
[en] 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 first 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.

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