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Mitogen and Stress-activated Protein Kinase 1 Negatively Regulates Hippocampal Neurogenesis

Neurogenesis in the subgranular zone (SGZ) of the adult hippocampus can be stimulated by a variety of means, including via exposure of experimental animals to an enriched environment that provides additional sensory, social, and motor stimulation. Tangible health and cognitive benefits accrue in enr...

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Autores principales: Olateju, Oladiran I., Morè, Lorenzo, Arthur, J. Simon C., Frenguelli, Bruno G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810160/
https://www.ncbi.nlm.nih.gov/pubmed/33246062
http://dx.doi.org/10.1016/j.neuroscience.2020.11.017
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author Olateju, Oladiran I.
Morè, Lorenzo
Arthur, J. Simon C.
Frenguelli, Bruno G.
author_facet Olateju, Oladiran I.
Morè, Lorenzo
Arthur, J. Simon C.
Frenguelli, Bruno G.
author_sort Olateju, Oladiran I.
collection PubMed
description Neurogenesis in the subgranular zone (SGZ) of the adult hippocampus can be stimulated by a variety of means, including via exposure of experimental animals to an enriched environment that provides additional sensory, social, and motor stimulation. Tangible health and cognitive benefits accrue in enriched animals, including the amelioration of signs modelling psychiatric, neurological and neurodegenerative conditions that affect humans, which may in part be due to enhanced production of neurons. A key factor in the neuronal response to enrichment is the release of brain-derived neurotrophic factor (BDNF) and the activation of the Mitogen-Activated Protein Kinase (MAPK) cascade, which can lead to the stimulation of neurogenesis. Mitogen- and Stress-Activated protein Kinase 1 (MSK1) is a nuclear enzyme downstream of BDNF and MAPK that regulates transcription. MSK1 has previously been implicated in both basal and stimulated neurogenesis on the basis of studies with mice lacking MSK1 protein. In the present study, using mice in which only the kinase activity of MSK1 is lacking, we show that the rate of cellular proliferation in the SGZ (Ki-67 staining) is unaffected by the MSK1 kinase-dead (KD) mutation, and no different from controls levels after five weeks of enrichment. However, compared to wild-type mice, the number of doublecortin (DCX)-positive cells was greater in both standard-housed and enriched MSK1 KD mice. These observations suggest that, while MSK1 does not influence the basal rate of proliferation of neuronal precursors, MSK1 negatively regulates the number of cells destined to become neurons, potentially as a homeostatic control on the number of new neurons integrating into the dentate gyrus.
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spelling pubmed-78101602021-01-22 Mitogen and Stress-activated Protein Kinase 1 Negatively Regulates Hippocampal Neurogenesis Olateju, Oladiran I. Morè, Lorenzo Arthur, J. Simon C. Frenguelli, Bruno G. Neuroscience Research Article Neurogenesis in the subgranular zone (SGZ) of the adult hippocampus can be stimulated by a variety of means, including via exposure of experimental animals to an enriched environment that provides additional sensory, social, and motor stimulation. Tangible health and cognitive benefits accrue in enriched animals, including the amelioration of signs modelling psychiatric, neurological and neurodegenerative conditions that affect humans, which may in part be due to enhanced production of neurons. A key factor in the neuronal response to enrichment is the release of brain-derived neurotrophic factor (BDNF) and the activation of the Mitogen-Activated Protein Kinase (MAPK) cascade, which can lead to the stimulation of neurogenesis. Mitogen- and Stress-Activated protein Kinase 1 (MSK1) is a nuclear enzyme downstream of BDNF and MAPK that regulates transcription. MSK1 has previously been implicated in both basal and stimulated neurogenesis on the basis of studies with mice lacking MSK1 protein. In the present study, using mice in which only the kinase activity of MSK1 is lacking, we show that the rate of cellular proliferation in the SGZ (Ki-67 staining) is unaffected by the MSK1 kinase-dead (KD) mutation, and no different from controls levels after five weeks of enrichment. However, compared to wild-type mice, the number of doublecortin (DCX)-positive cells was greater in both standard-housed and enriched MSK1 KD mice. These observations suggest that, while MSK1 does not influence the basal rate of proliferation of neuronal precursors, MSK1 negatively regulates the number of cells destined to become neurons, potentially as a homeostatic control on the number of new neurons integrating into the dentate gyrus. Elsevier Science 2021-01-01 /pmc/articles/PMC7810160/ /pubmed/33246062 http://dx.doi.org/10.1016/j.neuroscience.2020.11.017 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Olateju, Oladiran I.
Morè, Lorenzo
Arthur, J. Simon C.
Frenguelli, Bruno G.
Mitogen and Stress-activated Protein Kinase 1 Negatively Regulates Hippocampal Neurogenesis
title Mitogen and Stress-activated Protein Kinase 1 Negatively Regulates Hippocampal Neurogenesis
title_full Mitogen and Stress-activated Protein Kinase 1 Negatively Regulates Hippocampal Neurogenesis
title_fullStr Mitogen and Stress-activated Protein Kinase 1 Negatively Regulates Hippocampal Neurogenesis
title_full_unstemmed Mitogen and Stress-activated Protein Kinase 1 Negatively Regulates Hippocampal Neurogenesis
title_short Mitogen and Stress-activated Protein Kinase 1 Negatively Regulates Hippocampal Neurogenesis
title_sort mitogen and stress-activated protein kinase 1 negatively regulates hippocampal neurogenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810160/
https://www.ncbi.nlm.nih.gov/pubmed/33246062
http://dx.doi.org/10.1016/j.neuroscience.2020.11.017
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