The DOI matches its Crossref record; 65 of the 66 references it cites were found in a registry or an index.
Glycogen synthase kinase-3 regulates microglial migration, inflammation, and inflammation-induced neurotoxicity
Open accessAbstract
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 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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Metadata
- Authors
- Yuskaitis, C. J., & Jope, R. S.
- Affiliations
- University of Alabama at Birmingham (US)
- Corresponding author
- Jope, Richard S.
- Venue
- Cellular Signalling
- Publisher
- Elsevier BV
- Published
- 2009-02
- Volume
- 21
- Issue
- 2
- Pages
- 264-273
- ISSN
- 0898-6568 (ISSN-L)
- 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
- green
- www.ncbi.nlm.nih.gov
- 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 (medical) › 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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