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

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 (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.
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eLife, eLife Sciences Publication, 2017, 6, pp.e29996. 〈10.7554/eLife.29996.001〉
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Sylvie Remaud, Fernando Ortiz, Marine Perret-Jeanneret, Marie-Stéphane Aigrot, Jean-David Gothié, et al.. Transient hypothyroidism favors oligodendrocyte generation providing functional remyelination in the adult mouse brain. eLife, eLife Sciences Publication, 2017, 6, pp.e29996. 〈10.7554/eLife.29996.001〉. 〈hal-01613160〉

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