Involvement of GSK-3β Phosphorylation Through PI3-K-Akt in Cerebral Ischemia-Induced Neurogenesis in RatsReportar como inadecuado

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Molecular Neurobiology

pp 1–11

First Online: 19 November 2016Received: 28 July 2016Accepted: 02 November 2016


Glycogen synthase kinase GSK-3β, which is abundantly expressed in the central nervous system, regulates various cellular processes including gene expression, cell proliferation, and differentiation. However, involvement of GSK-3β in cerebral ischemia-induced endogenous neurogenesis is not yet fully understood. Appropriate strategies to prevent ischemic cell damage and subsequent severe sequelae are needed. The purpose of the present study was to determine the relationship between pathophysiological alteration of the GSK-3β signaling pathway and cerebral ischemia-induced endogenous neurogenesis in rats. Severe cerebral ischemia was produced by the injection of 700 microspheres into the right internal carotid artery of rats. We demonstrated that phosphorylation of GSK-3β at its Ser9 and that of Akt was significantly enhanced on day 7 after the cerebral ischemia, as was the number of NeuroD-positive cells. Treatment with a phosphatidylinositol 3-kinase PI3-K inhibitor decreased the cerebral ischemia-induced phosphorylation of Akt and that of GSK-3β at its Ser9. In addition, as the protein levels of insulin-like growth factor-1 IGF-1 and brain-derived neurotrophic factor BDNF were decreased, they might not have been essential for activation of the PI3-K-Akt-GSK-3β pathway after severe cerebral ischemia. Although it remains to be determined what factors activate this pathway, our results suggest that PI3K-Akt-dependent GSK-3β signaling and subsequent expression of NeuroD were involved in the neurogenesis elicited by cerebral ischemia.

KeywordsCerebral ischemia Neurogenesis GSK-3β PI3-K-Akt  Download fulltext PDF

Autor: Keishi Kisoh - Hideki Hayashi - Tsuyoshi Itoh - Mayumi Asada - Miho Arai - Bo Yuan - Kouichi Tanonaka - Norio Takagi


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