期刊
NEUROCHEMISTRY INTERNATIONAL
卷 61, 期 5, 页码 666-671出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2012.07.003
关键词
GSK-3; Lithium; Glia; Cytokine; beta-Catenin; Lipopolysaccharide
资金
- Research Council for Science, Engineering and Technology
- Science Foundation Ireland
Neuroinflammation has been shown to contribute to neurodegenerative and psychiatric disorders such as Alzheimer's disease and major depression due to the inappropriate release of pro-inflammatory cytokines from activated microglia. The precise molecular events that mediate cytokine release from glia remain unknown but we suggest that the serine/threonine kinase glycogen synthase kinase-3 (GSK-3) may be involved. The aim of this study therefore was to investigate the effect of lipopolysaccharide (LPS) on expression and activity of the GSK-3 beta isoform in glia, and to assess if GSK-3 mediates the LPS-induced change in inflammatory cytokine levels in culture medium from rat glial-enriched cortical cultures. GSK-3 beta was expressed in microglia and astrocytes, and stimulation of these cultures with LPS induced an increase in GSK-3 beta expression and activity, and in pro-inflammatory cytokine levels in culture media. We show that GSK-3 inhibition using a small molecule inhibitor SB216763 or the mood stabiliser lithium chloride reduced the LPS-induced elevated levels of pro-inflammatory cytokines present in culture media from rat glial-enriched cortical cultures. These results demonstrate a role for GSK-3 as a modulator of inflammatory cytokine levels in the brain, and contribute to a mechanistic insight into neurological disorders in which neuroinflammation is a characteristic feature. (C) 2012 Elsevier Ltd. All rights reserved.
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