Valproic acid, a mood stabilizer and anticonvulsant, protects rat cerebral cortical neurons from spontaneous cell death

A role of histone deacetylase inhibition

Mi Ra Jeong, Ryota Hashimoto, Vladimir V. Senatorov, Koichiro Fujimaki, Ming Ren, Min-Soo Lee, De Maw Chuang

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

We studied the neuroprotective effects of valproic acid (VPA), a primary mood stabilizer and anticonvulsant, in cultured rat cerebral cortical neurons (CCNs). CCNs underwent spontaneous cell death when their age increased in culture. As shown by mitochondrial activity and calcein-AM assays, treatment of CCNs with VPA starting from day 9 in vitro markedly increased viability and prolonged the life span of the cultures. The neuroprotective action of VPA was time-dependent and occurred at therapeutic levels with a maximal effect at about 0.5 mM. LiCl (1 mM) also protected CCNs from aging-induced, spontaneous cell death but less effectively. VPA-induced neuroprotection in aging CCN cultures was associated with a robust increase in histone H3 acetylation levels and the protective effect was mimicked by treatment with a histone deacetylase inhibitor, trichostatin A, but not by VPA analogs which are inactive in blocking histone deacetylase. Our results suggest a role of histone deacetylase inhibition in mediating the neuroprotective action of VPA.

Original languageEnglish
Pages (from-to)74-75
Number of pages2
JournalFEBS Letters
Volume542
Issue number1-3
DOIs
Publication statusPublished - 2003 May 8

Fingerprint

Histone Deacetylases
Valproic Acid
Cell death
Anticonvulsants
Neurons
Rats
Cell Death
trichostatin A
Aging of materials
Acetylation
Histone Deacetylase Inhibitors
Neuroprotective Agents
Cell culture
Histones
Inhibition (Psychology)
Assays

Keywords

  • Bipolar mood disorder
  • Cerebral cortical neuron
  • Histone deacetylase
  • Lithium
  • Neuroprotection
  • Valproate

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Valproic acid, a mood stabilizer and anticonvulsant, protects rat cerebral cortical neurons from spontaneous cell death : A role of histone deacetylase inhibition. / Jeong, Mi Ra; Hashimoto, Ryota; Senatorov, Vladimir V.; Fujimaki, Koichiro; Ren, Ming; Lee, Min-Soo; Chuang, De Maw.

In: FEBS Letters, Vol. 542, No. 1-3, 08.05.2003, p. 74-75.

Research output: Contribution to journalArticle

Jeong, Mi Ra ; Hashimoto, Ryota ; Senatorov, Vladimir V. ; Fujimaki, Koichiro ; Ren, Ming ; Lee, Min-Soo ; Chuang, De Maw. / Valproic acid, a mood stabilizer and anticonvulsant, protects rat cerebral cortical neurons from spontaneous cell death : A role of histone deacetylase inhibition. In: FEBS Letters. 2003 ; Vol. 542, No. 1-3. pp. 74-75.
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