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Cited by 242Neuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology ResearchPain Mechanisms and Treatments

Glycogen synthase kinase-3 regulates microglial migration, inflammation, and inflammation-induced neurotoxicity

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Yuskaitis, Christopher J., Jope, Richard S.·2009·Cellular Signalling
DOI 10.1016/j.cellsig.2008.10.014PMC PMC2630396
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Abstract

Microglia play a prominent role in the brain's inflammatory response to injury or infection by migrating to affected locations, secreting inflammatory molecules, and phagocytosing damaged tissue. However, because severe or chronic neuroinflammation exacerbates many neurological conditions, controlling microglia actions may provide therapeutic benefits in a diverse array of diseases. Since glycogen synthase kinase-3 (GSK3) promotes inflammatory responses in peripheral immune cells, we investigated if inhibitors of GSK3 attenuated microglia responses to inflammatory stimuli. Treatment of BV-2 microglia with GSK3 inhibitors greatly reduced the migration of microglia in both a scratch assay and in a transwell migration assay. Treatment of BV-2 microglia with lipopolysaccharide (LPS) stimulated the production of interleukin-6 and increased the expression of inducible nitric oxide synthase (iNOS) and NO production. Each of these microglia responses to inflammatory stimulation were greatly attenuated by GSK3 inhibitors. However, GSK3 inhibitors did not cause a general impairment of microglia functions, as the LPS-induced stimulated expression of cyclooxygenase-2 was unaltered. Regulation of microglia functions were also evident in cultured mouse hippocampal slices where GSK3 inhibitors reduced cytokine production and microglial migration, and provided protection from inflammation-induced neuronal toxicity. These findings demonstrate that GSK3 promotes microglial responses to inflammation and that the utilization of GSK3 inhibitors provides a means to limit the inflammatory actions of microglia.

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  • GSK-3 is a major regulator of the balance between pro- and anti-inflammatory mediators in immune cells, including microglia.

    “GSK-3 is a major regulator of the balance between the pro- and anti-inflammatory mediators in immune cells, including microglia [204].”

    From BDNF as a Promising Therapeutic Agent in Parkinson’s Disease (2020) · cites this paper as [204]

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Authors
Yuskaitis, C. J., & Jope, R. S.
Affiliations
University of Alabama at Birmingham (US)
Corresponding author
Jope, Richard S.
ORCID
Yuskaitis, Christopher J.
Venue
Cellular Signalling
Publisher
Elsevier BV
Published
2009-02
Volume
21
Issue
2
Pages
264-273
ISSN
0898-6568 (ISSN-L)
DOI
10.1016/j.cellsig.2008.10.014
PMC
PMC2630396
OpenAlex
W2054780831
Cited by
240
References
66
Citations by year
2026: 7 · 2025: 14 · 2024: 15 · 2023: 11 · 2022: 15 · 2021: 17 · 2020: 13 · 2019: 12 · 2018: 18 · 2017: 9 · 2016: 18 · 2015: 7 · 2014: 24 · 2013: 16 · 2012: 14
FWCI
6.56
Type
journal article
Language
en
Open access
Licence
Locations
  • Cellular Signalling (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • University of Dundee
  • National Institute on Aging (AG021045, R01AG021045)
  • National Institute of Mental Health (MH38752, R56MH038752, R01MH038752)
  • National Institute of Neurological Disorders and Stroke (NS47466, P30NS047466, R01NS037768, P30NS057098, NS3768, NS57098)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Keywords
glycogen synthase kinase-3, GSK-3 inhibitors, microglia, microglial migration, neuroinflammation, lipopolysaccharide, interleukin-6, inducible nitric oxide synthase, nitric oxide, cyclooxygenase-2, hippocampus, BV-2 cells
MeSH terms
Animals, Benzazepines, Cell Movement, Cells, Cultured, Indoles, Lipopolysaccharides, Lithium, Nitric Oxide, Oximes, Interleukin-6, Microglia, Inflammation Mediators, Nitric Oxide Synthase, Glycogen Synthase Kinase 3, Mice

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