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Elife. 2017 Sep 6;6. pii: e29996. doi: 10.7554/eLife.29996.

Transient hypothyroidism favors oligodendrocyte generation providing functional remyelination in the adult mouse brain.

Author information

1
Sorbonne Universités, Muséum d'Histoire Naturelle, Paris, France.
2
INSERM U1128, Paris, France.
3
Université Paris Descartes, Paris, France.
4
Mechanisms on Myelin Formation and Repair Lab, Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago, Chile.
5
Sorbonne Universités UPMC Univ Paris 06, Paris, France.
6
Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
7
Department of Medecine, Division of Endocrinology, Diabetes and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, United States.
8
AP-HP, Hôpital Pitié-Salpêtrière, Paris, France.
#
Contributed equally

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. The cellular basis for neuronal versus glial determination in progenitors involves asymmetric partitioning of EGFR and TRα1, expression of which favor glio- and neuro-genesis, 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.

KEYWORDS:

adult neural stem cell; cell fate; developmental biology; mouse; multiple sclerosis; oligodendrocytes; stem cells; thyroid hormone

PMID:
28875931
PMCID:
PMC5779229
DOI:
10.7554/eLife.29996
[Indexed for MEDLINE]
Free PMC Article

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