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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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
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:	Date Event 2020 Published 24 November 2020 Available 10 November 2020 Accepted
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:	Project/Grant ID RIOXX Funder Name Funder ID UNSPECIFIED International Brain Research Organization http://dx.doi.org/10.13039/501100001675 UNSPECIFIED International Society for Neurochemistry http://dx.doi.org/10.13039/501100008992 UNSPECIFIED Anderson Capelli Fund UNSPECIFIED

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