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Sci Rep. 2017 Aug 29;7(1):9794. doi: 10.1038/s41598-017-09621-3.

AhR-deficiency as a cause of demyelinating disease and inflammation.

Author information

1
INSERM UMR-S1124, Toxicologie Pharmacologie et Signalisation cellulaire, Paris, France.
2
Université Paris Descartes, 45 rue des Saints-Pères, 75006, Paris, France.
3
CNRS UMR8119, Centre de Neurophysique, Physiologie, Pathologie, Paris, France.
4
CNRS FR 3636, Glia-Glia and Glia-Neuron Interactions Group, Paris, France.
5
CNRS UMR8638 Chimie Organique, Médicinale et Extractive et Toxicologie Expérimentale, Paris, France.
6
Plate-Forme Séquençage et Génomique, Institut Cochin, Paris, France.
7
INSERM UMR-S1124, Toxicologie Pharmacologie et Signalisation cellulaire, Paris, France. xavier.coumoul@parisdescartes.fr.
8
Université Paris Descartes, 45 rue des Saints-Pères, 75006, Paris, France. xavier.coumoul@parisdescartes.fr.

Abstract

The Aryl hydrocarbon Receptor(AhR) is among the most important receptors which bind pollutants; however it also regulates signaling pathways independently of such exposure. We previously demonstrated that AhR is expressed during development of the central nervous system(CNS) and that its deletion leads to the occurrence of a congenital nystagmus. Objectives of the present study are to decipher the origin of these deficits, and to identify the role of the AhR in the development of the CNS. We show that the AhR-knockout phenotype develops during early infancy together with deficits in visual-information-processing which are associated with an altered optic nerve myelin sheath, which exhibits modifications in its lipid composition and in the expression of myelin-associated-glycoprotein(MAG), a cell adhesion molecule involved in myelin-maintenance and glia-axon interaction. In addition, we show that the expression of pro-inflammatory cytokines is increased in the impaired optic nerve and confirm that inflammation is causally related with an AhR-dependent decreased expression of MAG. Overall, our findings demonstrate the role of the AhR as a physiological regulator of myelination and inflammatory processes in the developing CNS. It identifies a mechanism by which environmental pollutants might influence CNS myelination and suggest AhR as a relevant drug target for demyelinating diseases.

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