Circadian glucocorticoid oscillations preserve a population of adult hippocampal neural stem cells in the aging brain.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_1E000CE7EA8B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Circadian glucocorticoid oscillations preserve a population of adult hippocampal neural stem cells in the aging brain.
Périodique
Molecular psychiatry
Auteur⸱e⸱s
Schouten M., Bielefeld P., Garcia-Corzo L., Passchier EMJ, Gradari S., Jungenitz T., Pons-Espinal M., Gebara E., Martín-Suárez S., Lucassen P.J., De Vries H.E., Trejo J.L., Schwarzacher S.W., De Pietri Tonelli D., Toni N., Mira H., Encinas J.M., Fitzsimons C.P.
ISSN
1476-5578 (Electronic)
ISSN-L
1359-4184
Statut éditorial
Publié
Date de publication
07/2020
Peer-reviewed
Oui
Volume
25
Numéro
7
Pages
1382-1405
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
A decrease in adult hippocampal neurogenesis has been linked to age-related cognitive impairment. However, the mechanisms involved in this age-related reduction remain elusive. Glucocorticoid hormones (GC) are important regulators of neural stem/precursor cells (NSPC) proliferation. GC are released from the adrenal glands in ultradian secretory pulses that generate characteristic circadian oscillations. Here, we investigated the hypothesis that GC oscillations prevent NSPC activation and preserve a quiescent NSPC pool in the aging hippocampus. We found that hippocampal NSPC populations lacking expression of the glucocorticoid receptor (GR) decayed exponentially with age, while GR-positive populations decayed linearly and predominated in the hippocampus from middle age onwards. Importantly, GC oscillations controlled NSPC activation and GR knockdown reactivated NSPC proliferation in aged mice. When modeled in primary hippocampal NSPC cultures, GC oscillations control cell cycle progression and induce specific genome-wide DNA methylation profiles. GC oscillations induced lasting changes in the methylation state of a group of gene promoters associated with cell cycle regulation and the canonical Wnt signaling pathway. Finally, in a mouse model of accelerated aging, we show that disruption of GC oscillations induces lasting changes in dendritic complexity, spine numbers and morphology of newborn granule neurons. Together, these results indicate that GC oscillations preserve a population of GR-expressing NSPC during aging, preventing their activation possibly by epigenetic programming through methylation of specific gene promoters. Our observations suggest a novel mechanism mediated by GC that controls NSPC proliferation and preserves a dormant NSPC pool, possibly contributing to a neuroplasticity reserve in the aging brain.
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/06/2019 13:50
Dernière modification de la notice
10/07/2020 6:21
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