Valproic acid induces microglial dysfunction, not apoptosis, in human glial cultures
Open accessAbstract
Valproic acid (VPA) is widely used for the treatment of mood disorders and epilepsy, but its mechanism of action is unclear. In vivo and in vitro studies using rodent models have demonstrated that VPA has both neuroprotective and neurotrophic effects. These beneficial effects are, in part, through modulation of glial cell function. Recently, we and others have shown that VPA selectively induces caspase-3 mediated apoptosis in rodent microglial cells. However, the effect of VPA on human microglia has not been tested. In this study, using microglia derived from adult human brains, we demonstrate that VPA does not induce microglial apoptosis as determined by the absence of caspase-3 cleavage. However, VPA does partially decrease the expression of the microglial markers PU.1 and CD45, as well as dramatically reducing microglial phagocytosis. Due to the many roles of microglia in the brain, these VPA-induced alterations in microglial phenotype could potentially have major effects on physiological and pathological actions of these cells.
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Microglial phagocytosis is regulated via an epigenetic mechanism.
“suggesting the its regulation of microglial phagocytosis via epigenetic mechanism [36-38].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [38]
Valproic acid treatment of primary adult human microglia reduces phagocytic capacity and expression of PU.1 and CD45.
“Valproic acid treatment, which selectively inhibits the catalytic activity of class I HDACs and induces proteasomal degradation of HDAC2, of primary adult human microglia reduces phagocytic capacity and expression of PU.1 and CD45, suggesting the its regulation of microglial phagocytosis via epigenetic mechanism [36-38].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [38]
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- Authors
- Gibbons, H. M., Smith, A. M., Teoh, H. H., Bergin, P. M., Mee, E. W., Faull, R. L. M., & Dragunow, M.
- Affiliations
- University of Auckland (NZ)
- Corresponding author
- Dragunow, Mike
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 41
- Issue
- 1
- Pages
- 96-103
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W1998694769
- Cited by
- 49
- References
- 46
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 7 · 2013: 9 · 2012: 2
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- ResearchSpace (University of Auckland) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- valproic acid, microglial dysfunction, microglial apoptosis, caspase-3, human microglia, microglial phagocytosis, PU.1, CD45, microglial phenotype, glial cells, epilepsy, mood disorders
- MeSH terms
- Proto-Oncogene Protein Spi-1, Adult, Anticonvulsants, Cells, Cultured, Humans, Phagocytosis, Proto-Oncogene Proteins, Valproic Acid, Trans-Activators, Apoptosis, Leukocyte Common Antigens, Microglia, Caspase 3
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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