Journal of Inherited Metabolic Disease

, Volume 33, Issue 2, pp 113–120 | Cite as

Oligodendrocyte development and myelinogenesis are not impaired by high concentrations of phenylalanine or its metabolites

  • Renaud Schoemans
  • Marie-Stéphane Aigrot
  • Chaohong Wu
  • Raphaël Marée
  • Pengyu Hong
  • Shibeshi Belachew
  • Claire Josse
  • Catherine Lubetzki
  • Vincent Bours
Original Article


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.


Corpus Callosum Myelin Basic Protein Myelin Sheath Large Neutral Amino Acid Oligodendrocyte Development 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

List of abbreviations




Phenylalanine hydroxylase










Large neutral amino acids


Oligodendrocyte progenitor cells


Subventricular zone



The authors thank the Imaging Platform, the SPF Animal Facility, and the Neurosciences Department from GIGA-Research for their experimental help. We also thank Olympus Belgium N.V. for providing the Cell^R system.

Competing interest

None declared.


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Copyright information

© SSIEM and Springer 2010

Authors and Affiliations

  • Renaud Schoemans
    • 1
  • Marie-Stéphane Aigrot
    • 2
  • Chaohong Wu
    • 3
  • Raphaël Marée
    • 4
  • Pengyu Hong
    • 3
  • Shibeshi Belachew
    • 5
  • Claire Josse
    • 1
  • Catherine Lubetzki
    • 2
  • Vincent Bours
    • 1
    • 6
    • 7
  1. 1.Human Genetics, GIGA-ResearchUniversity of LiègeLiègeBelgium
  2. 2.Cr-Icm, Inserm 711, UPMCParisFrance
  3. 3.Michtom School of Computer Science, Volen Center for Complex Systems, Room 261Brandeis UniversityWalthamUSA
  4. 4.Bioinformatics platform, GIGA-ResearchUniversity of LiègeLiègeBelgium
  5. 5.Neurosciences, GIGA-ResearchUniversity of LiègeLiègeBelgium
  6. 6.Genetics Center, CHU LiègeLiègeBelgium
  7. 7.Department of Genetics, CHU LiègeUniversité de Liège B34Liège, BelgiqueBelgium

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