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

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 number...

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Autores principales: Micheli, Laura, D’Andrea, Giorgio, Ceccarelli, Manuela, Ferri, Alessandra, Scardigli, Raffaella, Tirone, Felice
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374340/
https://www.ncbi.nlm.nih.gov/pubmed/30792628
http://dx.doi.org/10.3389/fncel.2019.00010
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author Micheli, Laura
D’Andrea, Giorgio
Ceccarelli, Manuela
Ferri, Alessandra
Scardigli, Raffaella
Tirone, Felice
author_facet Micheli, Laura
D’Andrea, Giorgio
Ceccarelli, Manuela
Ferri, Alessandra
Scardigli, Raffaella
Tirone, Felice
author_sort Micheli, Laura
collection PubMed
description 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. Stem cells, notably, are not induced to proliferate by running in wild-type (WT) mice. Moreover, p16Ink4a-null progenitor cells were increased by running significantly above the number observed in WT mice. The new stem and progenitor cells generated new neurons, and continued to actively proliferate in p16Ink4a-null mice longer than in the WT after cessation of exercise. Thus, p16Ink4a prevents aging dentate gyrus stem cells from being activated by exercise. Therefore, p16Ink4a may play a role in the maintenance of dentate gyrus stem cells after stimulus, by keeping a reserve of their self-renewal capacity during aging.
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spelling pubmed-63743402019-02-21 p16Ink4a Prevents the Activation of Aged Quiescent Dentate Gyrus Stem Cells by Physical Exercise Micheli, Laura D’Andrea, Giorgio Ceccarelli, Manuela Ferri, Alessandra Scardigli, Raffaella Tirone, Felice Front Cell Neurosci Neuroscience 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. Stem cells, notably, are not induced to proliferate by running in wild-type (WT) mice. Moreover, p16Ink4a-null progenitor cells were increased by running significantly above the number observed in WT mice. The new stem and progenitor cells generated new neurons, and continued to actively proliferate in p16Ink4a-null mice longer than in the WT after cessation of exercise. Thus, p16Ink4a prevents aging dentate gyrus stem cells from being activated by exercise. Therefore, p16Ink4a may play a role in the maintenance of dentate gyrus stem cells after stimulus, by keeping a reserve of their self-renewal capacity during aging. Frontiers Media S.A. 2019-02-07 /pmc/articles/PMC6374340/ /pubmed/30792628 http://dx.doi.org/10.3389/fncel.2019.00010 Text en Copyright © 2019 Micheli, D’Andrea, Ceccarelli, Ferri, Scardigli and Tirone. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Micheli, Laura
D’Andrea, Giorgio
Ceccarelli, Manuela
Ferri, Alessandra
Scardigli, Raffaella
Tirone, Felice
p16Ink4a Prevents the Activation of Aged Quiescent Dentate Gyrus Stem Cells by Physical Exercise
title p16Ink4a Prevents the Activation of Aged Quiescent Dentate Gyrus Stem Cells by Physical Exercise
title_full p16Ink4a Prevents the Activation of Aged Quiescent Dentate Gyrus Stem Cells by Physical Exercise
title_fullStr p16Ink4a Prevents the Activation of Aged Quiescent Dentate Gyrus Stem Cells by Physical Exercise
title_full_unstemmed p16Ink4a Prevents the Activation of Aged Quiescent Dentate Gyrus Stem Cells by Physical Exercise
title_short p16Ink4a Prevents the Activation of Aged Quiescent Dentate Gyrus Stem Cells by Physical Exercise
title_sort p16ink4a prevents the activation of aged quiescent dentate gyrus stem cells by physical exercise
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374340/
https://www.ncbi.nlm.nih.gov/pubmed/30792628
http://dx.doi.org/10.3389/fncel.2019.00010
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