title: Mitogen and stress-activated kinases 1/2 regulate ischemia-induced hippocampal progenitor cell proliferation and neurogenesis.
abstract: Pathophysiological conditions such as cerebral ischemia trigger the production of new neurons from the neurogenic niche within the subgranular zone (SGZ) of the dentate gyrus. The functional significance of ischemia-induced neurogenesis is believed to be the regeneration of lost cells, thus contributing to post-ischemia recovery. However, the cell signaling mechanisms by which this process is regulated are still under investigation. Here, we investigated the role of mitogen and stress-activated protein kinases (MSK1/2) in the regulation of progenitor cell proliferation and neurogenesis after cerebral ischemia. Using the endothelin-1 model of ischemia, wild-type (WT) and MSK1(-/-)/MSK2(-/-) (MSK dKO) mice were injected with BrdU and sacrificed 2 days, 4 weeks, or 6 weeks later for the analysis of progenitor cell proliferation, neurogenesis, and neuronal morphology, respectively. We report a decrease in SGZ progenitor cell proliferation in MSK dKO mice compared to WT mice. Moreover, MSK dKO mice exhibited reduced neurogenesis and a delayed maturation of ischemia-induced newborn neurons. Further, structural analysis of neuronal arborization revealed reduced branching complexity in MSK dKO compared to WT mice. Taken together, this dataset suggests that MSK1/2 plays a significant role in the regulation of ischemia-induced progenitor cell proliferation and neurogenesis. Ultimately, revealing the cell signaling mechanisms that promote neuronal recovery will lead to novel pharmacological approaches for the treatment of neurodegenerative diseases such as cerebral ischemia.
authors.affiliation: Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: K
authors.initials: K
authors.lastname: Karelina
authors.affiliation: Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Division of Pharmacology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: D
authors.initials: D
authors.lastname: Alzate-Correa
authors.affiliation: Division of Pharmacology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Wheaton
authors.affiliation: Division of Pharmacology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Hoyt
authors.affiliation: MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom.
authors.forename: J S C
authors.initials: JS
authors.lastname: Arthur
authors.affiliation: Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA. Electronic address: obrietan.1@osu.edu.
authors.forename: K
authors.initials: K
authors.lastname: Obrietan
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology* / Q000473:pathology; D018891:Dentate Gyrus / Q000201:enzymology* / Q000473:pathology; D004195:Disease Models, Animal; D019332:Endothelin-1; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000201:enzymology* / Q000473:pathology; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism*; D055153:Stem Cell Niche / Q000502:physiology
chemical_list: D019332:Endothelin-1; D049452:Green Fluorescent Proteins; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C485459:Rps6ka4 protein, mouse; C116919:mitogen and stress-activated protein kinase 1
keywords: MAPK; MSK; hippocampus; ischemia; neurogenesis; subgranular zone