Mitogen and stress-activated protein kinase 1 negatively regulates hippocampal neurogenesis
| Autor: | J. Simon C. Arthur, Bruno G. Frenguelli, Oladiran I. Olateju, Lorenzo Morè |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Doublecortin Protein MSK1 hippocampus B140 Neurogenesis Ribosomal Protein S6 Kinases 90-kDa Subgranular zone Mice 03 medical and health sciences 0302 clinical medicine Neurotrophic factors medicine Animals Mitogen-Activated Protein Kinase 8 Kinase activity Protein kinase A Environmental enrichment MSK1 Mitogen- and Stress-Activated protein Kinase 1 biology General Neuroscience Dentate gyrus DCX doublecortin DG dentate gyrus SGZ subgranular zone MAPK Mitogen-Activated Protein Kinase QP Doublecortin Cell biology BDNF 030104 developmental biology medicine.anatomical_structure nervous system BDNF brain-derived neurotrophic factor environmental enrichment biology.protein SGZ 030217 neurology & neurosurgery Research Article |
| Zdroj: | Neuroscience |
| ISSN: | 0306-4522 |
| Popis: | Graphical abstract The dentate gyrus (DG) in rodent hippocampus is a site of neurogenesis. Newly developing neurons can be identified through immunostaining for doublecortin (DCX). We have found that genetic inactivation of the kinase activity of MSK1 (in red) results in an increase in the number of DCX-positive (DCX+) cells. This suggests that MSK1 negatively regulates neurogenesis in the subgranular zone, potentially to limit the number of new neurons in the dentate gyrus and maintain the stability of neuronal networks. Highlights • Neurogenesis in the subgranular zone of the hippocampal dentate gyrus was examined. • Ki-67 staining was not affected by the loss of MSK1 kinase activity. • DCX staining was increased in the MSK1 kinase dead mutant mouse. • MSK1 may negatively regulate neurogenesis to maintain stable neuronal networks. 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. |
| Databáze: | OpenAIRE |
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