p16Ink4a Prevents the Activation of Aged Quiescent Dentate Gyrus Stem Cells by Physical Exercise

Frontiers in Cellular Neuroscience
Laura MicheliFelice Tirone

Abstract

In the neurogenic niches-the dentate gyrus of the hippocampus and the subventricular zone (SVZ) adjacent to lateral ventricles-stem cells continue to divide during adulthood, generating progenitor cells and new neurons, and to self-renew, thus maintaining the stem cell pool. During aging, the numbers of stem/progenitor cells in the neurogenic niches are reduced. The preservation of the neurogenic pool is committed to a number of antiproliferative genes, with the role of maintaining the quiescence of neural cells. The cyclin-dependent kinase inhibitor p16Ink4a, whose expression increases with age, controls the expansion of SVZ aging stem cells, since in mice its deficiency prevents the decline of neurogenesis in SVZ. No change of neurogenesis is however observed in the p16Ink4a-null dentate gyrus. Here, we hypothesized that p16Ink4a plays a role as a regulator of the self-renewal of the stem cell pool also in the dentate gyrus, and to test this possibility we stimulated the dentate gyrus neural cells of p16Ink4a-null aging mice with physical exercise, a powerful neurogenic activator. We observed that running highly induced the generation of new stem cells in the p16Ink4a-null dentate gyrus, forcing them to exit from quiescence. ...Continue Reading

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Citations

Nov 17, 2019·Cells·Christian SchmeerOtto W Witte
Feb 7, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Giorgio D'AndreaFelice Tirone
May 10, 2019·Frontiers in Cell and Developmental Biology·Anja Urbach, Otto W Witte
Jul 30, 2020·Cell Stem Cell·Paloma Navarro NegredoAnne Brunet
Oct 26, 2021·Frontiers in Neuroscience·Alexandra PalmerGareth J Sanger

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Methods Mentioned

BETA
Genotyping
PCR
confocal microscopy
Knockout

Software Mentioned

Power
XLSTAT
Delta
StatView

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