title: Ribosomal S6 kinase regulates ischemia-induced progenitor cell proliferation in the adult mouse hippocampus.
abstract: Ischemia-induced progenitor cell proliferation is a prominent example of the adult mammalian brain's ability to regenerate injured tissue resulting from pathophysiological processes. In order to better understand and exploit the cell signaling mechanisms that regulate ischemia-induced proliferation, we examined the role of the p42/44 mitogen-activated protein kinase (MAPK) cascade effector ribosomal S6 kinase (RSK) in this process. Here, using the endothelin-1 ischemia model in wild type mice, we show that the activated form of RSK is expressed in the progenitor cells of the subgranular zone (SGZ) after intrahippocampal cerebral ischemia. Further, RSK inhibition significantly reduces ischemia-induced SGZ progenitor cell proliferation. Using the neurosphere assay, we also show that both SGZ- and subventricular zone (SVZ)-derived adult neural stem cells (NSC) exhibit a significant reduction in proliferation in the presence of RSK and MAPK inhibitors. Taken together, these data reveal RSK as a regulator of ischemia-induced progenitor cell proliferation, and as such, suggest potential therapeutic value may be gained by specifically targeting the regulation of RSK in the progenitor cell population of the SGZ.
authors.affiliation: Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Kate
authors.initials: K
authors.lastname: Karelina
authors.affiliation: Division of Pharmacology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Diego
authors.initials: D
authors.lastname: Alzate-Correa
authors.affiliation: Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA. Electronic address: obrietan.1@osu.edu.
authors.forename: Karl
authors.initials: K
authors.lastname: Obrietan
mesh_terms: D053687:Adult Stem Cells / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D002545:Brain Ischemia / Q000139:chemically induced / Q000473:pathology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000009:adverse effects / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005452:Fluoresceins; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*; D013997:Time Factors
chemical_list: D019332:Endothelin-1; D004791:Enzyme Inhibitors; D005452:Fluoresceins; D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins; C435731:fluoro jade; D019893:Ribosomal Protein S6 Kinases; D001973:Bromodeoxyuridine
keywords: Adult progenitor cell proliferation; Endothelin-1; Ischemia; RSK