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Cited by 262Neuroinflammation and Neurodegeneration MechanismsHistone Deacetylase Inhibitors ResearchParkinson's Disease Mechanisms and Treatments

The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.

Valproic acid and other histone deacetylase inhibitors induce microglial apoptosis and attenuate lipopolysaccharide-induced dopaminergic neurotoxicity

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Chen, P.S., Wang, C.-C., Bortner, C.D., Peng, G.-S., Wu, X., Pang, H., Lu, R.-B., Gean, P.-W., Chuang, D.-M., Hong, J.-S.·2007·Neuroscience
DOI 10.1016/j.neuroscience.2007.06.053PMC PMC2741413
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Abstract

Valproic acid (VPA), a widely prescribed drug for seizures and bipolar disorder, has been shown to be an inhibitor of histone deacetylase (HDAC). Our previous study has demonstrated that VPA pretreatment reduces lipopolysaccharide (LPS)-induced dopaminergic (DA) neurotoxicity through the inhibition of microglia over-activation. The aim of this study was to determine the mechanism underlying VPA-induced attenuation of microglia over-activation using rodent primary neuron/glia or enriched glia cultures. Other histone deacetylase inhibitors (HDACIs) were compared with VPA for their effects on microglial activity. We found that VPA induced apoptosis of microglia cells in a time- and concentration-dependent manner. VPA-treated microglial cells showed typical apoptotic hallmarks including phosphatidylserine externalization, chromatin condensation and DNA fragmentation. Further studies revealed that trichostatin A (TSA) and sodium butyrate (SB), two structurally dissimilar HDACIs, also induced microglial apoptosis. The apoptosis of microglia was accompanied by the disruption of mitochondrial membrane potential and the enhancement of acetylation levels of the histone H3 protein. Moreover, pretreatment with SB or TSA caused a robust decrease in LPS-induced pro-inflammatory responses and protected DA neurons from damage in mesencephalic neuron-glia cultures. Taken together, our results shed light on a novel mechanism whereby HDACIs induce neuroprotection and underscore the potential utility of HDACIs in preventing inflammation-related neurodegenerative disorders such as Parkinson's disease.

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Authors
Chen, P. S., Wang, C.-C., Bortner, C. D., Peng, G.-S., Wu, X., Pang, H., Lu, R.-B., Gean, P.-W., Chuang, D.-M., & Hong, J.-S.
Affiliations
  • National Institutes of Health (US)
  • Tri-Service General Hospital (TW)
  • National Cheng Kung University (TW)
Corresponding author
Hong, J.-S.
ORCID
Venue
Neuroscience
Publisher
Elsevier BV
Published
2007-10
Volume
149
Issue
1
Pages
203-212
ISSN
0306-4522 (ISSN-L)
DOI
10.1016/j.neuroscience.2007.06.053
PMC
PMC2741413
OpenAlex
W2039098916
Cited by
262
References
43
Citations by year
2026: 5 · 2025: 4 · 2024: 10 · 2023: 12 · 2022: 14 · 2021: 14 · 2020: 10 · 2019: 13 · 2018: 13 · 2017: 13 · 2016: 14 · 2015: 22 · 2014: 18 · 2013: 17 · 2012: 16
FWCI
9.57
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Environmental Health Sciences (Z01ES090082)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
  • Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords
valproic acid, histone deacetylase inhibitors, microglial apoptosis, lipopolysaccharide, dopaminergic neurotoxicity, trichostatin A, sodium butyrate, mitochondrial membrane potential, histone H3 acetylation, neuroinflammation, neuroprotection, Parkinson's disease, microglial activation
MeSH terms
Animals, Animals, Newborn, Brain, Cell Cycle, Cells, Cultured, Dopamine, Dose-Response Relationship, Drug, Enzyme Inhibitors, Female, Lipopolysaccharides, Neuroglia, Neurons, Nitrites, Pregnancy, Rats, Inbred F344, Tumor Necrosis Factor-alpha, Valproic Acid, Apoptosis, In Situ Nick-End Labeling, Rats, Histone Acetyltransferases, Membrane Potential, Mitochondrial

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