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

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_1E000CE7EA8B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Circadian glucocorticoid oscillations preserve a population of adult hippocampal neural stem cells in the aging brain.
Journal
Molecular psychiatry
Author(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
Publication state
Published
Issued date
07/2020
Peer-reviewed
Oui
Volume
25
Number
7
Pages
1382-1405
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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
Yes
Create date
25/06/2019 13:50
Last modification date
10/07/2020 6:21
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