Transient hypothyroidism favors oligodendrocyte generation providing functional remyelination in the adult mouse brain
- Muséum d'Histoire Naturelle, Sorbonne Universités, France
- INSERM U1128, France
- Sorbonne Universités UPMC Univ Paris 06, Inserm, CNRS, France
- Institute of Experimental Medicine, Hungarian Academy of Sciences, Hungary
Abstract
In the adult brain, both neurons and oligodendrocytes can be generated from neural stem cells located within the Sub-Ventricular Zone (SVZ). Physiological signals regulating neuronal versus glial fate are largely unknown. Here we report that a thyroid hormone (T3)-free window, with or without a demyelinating insult, provides a favorable environment for SVZ-derived oligodendrocyte progenitor generation. After demyelination, oligodendrocytes derived from these newly-formed progenitors provide functional remyelination, restoring normal conduction speed. The cellular basis for neuronal versus glial determination in progenitors involves asymmetric partitioning of EGFR and TRα1, expression of which favor glio-and neurogenesis, respectively. Moreover, EGFR+ oligodendrocyte progenitors, but not neuroblasts, express high levels of a T3-inactivating deiodinase, Dio3. Thus, TRα absence with high levels of Dio3 provides double-pronged blockage of T3 action during glial lineage commitment. These findings not only transform our understanding of how T3 orchestrates adult brain lineage decisions, but also provide potential insight into demyelinating disorders.
Article and author information
Author details
Funding
Association Française contre les Myopathies
- Sylvie REMAUD
- Barbara Demeneix
European Commission
- Barbara Demeneix
Agence Nationale de la Recherche
- Sylvie REMAUD
- Bernard Zalc
- Barbara Demeneix
Fondation pour la Recherche Médicale
- Maria Cecilia Angulo
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experimental procedures involving mice in our study were approved by the French Ministry of Agriculture (authorization number, 01169.02).
Copyright
© 2017, REMAUD et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Transient hypothyroidism favors oligodendrocyte generation providing functional remyelination in the adult mouse brain
eLife 6:e29996.
https://doi.org/10.7554/eLife.29996
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