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Adult neural stem cell fate is determined by thyroid hormone activation of mitochondrial metabolism.

Abstract：

OBJECTIVE:In the adult brain, neural stem cells (NSCs) located in the subventricular zone (SVZ) produce both neuronal and glial cells. Thyroid hormones (THs) regulate adult NSC differentiation towards a neuronal phenotype, but also have major roles in mitochondrial metabolism. As NSC metabolism relies mainly on glycolysis, whereas mature cells preferentially use oxidative phosphorylation, we studied how THs and mitochondrial metabolism interact on NSC fate determination. METHODS:We used a mitochondrial membrane potential marker in vivo to analyze mitochondrial activity in the different cell types in the SVZ of euthyroid and hypothyroid mice. Using primary adult NSC cultures, we analyzed ROS production, SIRT1 expression, and phosphorylation of DRP1 (a mitochondrial fission mediator) as a function of TH availability. RESULTS:We observed significantly higher mitochondrial activity in cells adopting a neuronal phenotype in vivo in euthyroid mice. However, prolonged hypothyroidism reduced not only neuroblast numbers but also their mitochondrial activity. In vitro studies showed that TH availability favored a neuronal phenotype and that blocking mitochondrial respiration abrogated TH-induced neuronal fate determination. DRP1 phosphorylation was preferentially activated in cells within the neuronal lineage and was stimulated by TH availability. CONCLUSIONS:These results indicate that THs favor NSC fate choice towards a neuronal phenotype in the adult mouse SVZ through effects on mitochondrial metabolism.

journal_name

Mol Metab

journal_title

Molecular metabolism

authors

Gothié JD,Sébillot A,Luongo C,Legendre M,Nguyen Van C,Le Blay K,Perret-Jeanneret M,Remaud S,Demeneix BA

doi

10.1016/j.molmet.2017.08.003

subject

Has Abstract

pub_date

2017-11-01 00:00:00

pages

1551-1561

issue

11

issn

2212-8778

pii

S2212-8778(17)30568-9

journal_volume

6

pub_type

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