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MSK1 negatively regulates hippocampal neurogenesis
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Olateju, Oladiran, Morè, Lorenzo, Arthur, J. Simon C. and Frenguelli, Bruno G. (2020) MSK1 negatively regulates hippocampal neurogenesis. Neuroscience . doi:10.1016/j.neuroscience.2020.11.017 (In Press)
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WRAP-MSK1-negatively-regulates-Frenguelli-2020.pdf - Accepted Version Embargoed item. Restricted access to Repository staff only until 24 November 2021. Contact author directly, specifying your specific needs. - Requires a PDF viewer. Available under License Creative Commons Attribution Non-commercial No Derivatives 4.0. Download (2964Kb) |
Official URL: http://dx.doi.org/10.1016/j.neuroscience.2020.11.0...
Abstract
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 BDNF and the activation of the MAPK cascade, which can lead to the stimulation of neurogenesis. 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.
Item Type: | Journal Article | ||||||||||||
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Subjects: | Q Science > QP Physiology | ||||||||||||
Divisions: | Faculty of Science > Life Sciences (2010- ) | ||||||||||||
Library of Congress Subject Headings (LCSH): | Dentate gyrus, Hippocampus (Brain), Nervous system -- Regeneration, Neuroplasticity | ||||||||||||
Journal or Publication Title: | Neuroscience | ||||||||||||
Publisher: | Elsevier | ||||||||||||
ISSN: | 0306-4522 | ||||||||||||
Official Date: | 2020 | ||||||||||||
Dates: |
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Date of first compliant deposit: | 26 November 2020 | ||||||||||||
DOI: | 10.1016/j.neuroscience.2020.11.017 | ||||||||||||
Status: | Peer Reviewed | ||||||||||||
Publication Status: | In Press | ||||||||||||
Access rights to Published version: | Restricted or Subscription Access | ||||||||||||
RIOXX Funder/Project Grant: |
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