Mitogen and Stress-activated Protein Kinase 1 negatively regulates hippocampal neurogenesis

Oladiran I. Olateju, Lorenzo Morè, J. Simon C. Arthur, Bruno G. Frenguelli (Lead / Corresponding author)

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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.

Original languageEnglish
Pages (from-to)228-234
Number of pages7
JournalNeuroscience
Volume452
Early online date24 Nov 2020
DOIs
Publication statusPublished - 1 Jan 2021

Keywords

  • MSK1
  • BDNF
  • neurogenesis
  • SGZ
  • environmental enrichment
  • hippocampus

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