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 (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 TR?1, 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, TR? 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.

SUBMITTER: Remaud S 

PROVIDER: S-EPMC5779229 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature