Valproate protects dopaminergic neurons in midbrain neuron/glia cultures by stimulating the release of neurotrophic factors from astrocytes

P. S. Chen, G. S. Peng, G. Li, S. Yang, X. Wu, C. C. Wang, B. Wilson, R. B. Lu, P. W. Gean, D. M. Chuang, J. S. Hong

研究成果: Article同行評審

277 引文 斯高帕斯(Scopus)

摘要

Valproate (VPA), one of the mood stabilizers and antiepileptic drugs, was recently found to inhibit histone deacetylases (HDAC). Increasing reports demonstrate that VPA has neurotrophic effects in diverse cell types including midbrain dopaminergic (DA) neurons. However, the origin and nature of the mediator of the neurotrophic effects are unclear. We have previously demonstrated that VPA prolongs the survival of midbrain DA neurons in lipopolysaccharide (LPS)-treated neuron-glia cultures through the inhibition of the release of pro-inflammatory factors from microglia. In this study, we report that VPA upregulates the expression of neurotrophic factors, including glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) from astrocytes and these effects may play a major role in mediating VPA-induced neurotrophic effects on DA neurons. Moreover, VPA pretreatment protects midbrain DA neurons from LPS or 1-methyl-4- phenylpyridinium (MPP+)-induced neurotoxicity. Our study identifies astrocyte as a novel target for VPA to induce neurotrophic and neuroprotective actions in rat midbrain and shows a potential new role of cellular interactions between DA neurons and astrocytes. The neurotrophic and neuroprotective effects of VPA also suggest a utility of this drug for treating neurodegenerative disorders including Parkinson's disease. Moreover, the neurotrophic effects of VPA may contribute to the therapeutic action of this drug in treating bipolar mood disorder that involves a loss of neurons and glia in discrete brain areas.

原文English
頁(從 - 到)1116-1125
頁數10
期刊Molecular Psychiatry
11
發行號12
DOIs
出版狀態Published - 2006 十二月

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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