Open AccessTransient hypothyroidism favors oligodendrocyte generation providing functional remyelination in the adult mouse brain
Author(s) -
Sylvie Remaud,
Fernando López Ortiz,
Marine Perret-Jeanneret,
Marie-Stéphane Aigrot,
Jean-David Gothié,
Ronald M. Lechan,
Zsuzsanna Kvárta-Papp,
Balázs Gereben,
Dominique Langui,
Catherine Lubetzki,
María Cecilia Angulo,
Bernard Zalc,
Barbara A. Demeneix
Publication year - 2017
Publication title -
hal (le centre pour la communication scientifique directe)
Language(s) - English
DOI - 10.7554/elife.29996.001
Subject(s) - remyelination , oligodendrocyte , neuroscience , transient (computer programming) , medicine , psychology , myelin , central nervous system , computer science , operating system
International audienceIn 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 (T 3)-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 TRa1, expression of which favor glio-and neuro-genesis, respectively. Moreover, EGFR + oligodendrocyte progenitors, but not neuroblasts, express high levels of a T 3-inactivating deiodinase, Dio3. Thus, TRa absence with high levels of Dio3 provides double-pronged blockage of T 3 action during glial lineage commitment. These findings not only transform our understanding of how T 3 orchestrates adult brain lineage decisions, but also provide potential insight into demyelinating disorders