Valproic acid, a mood stabilizer and anticonvulsant, protects rat cerebral cortical neurons from spontaneous cell death: a role of histone deacetylase inhibition

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• 作者：Jeong ; Mi Ra ; Hashimoto ; Ryota ; Senatorov ; Vladimir V. ; Fujimaki ; Koichiro ; Ren ; Ming ; Lee ; Min Soo ; et. al.
• 关键词：Valproate ; Neuroprotection ; Cerebral cortical neuron ; Histone deacetylase ; Bipolar mood disorder ; Lithium ; CCNs ; cerebral cortical neurons ; HDAC ; histone deacetylase ; MTT ; 3-(4 ; 5-dimethylthiazol-2-yl)-2 ; 5-diphenyltetrazolium bromide ; 2M2P ; 2-methyl-2-pent
• 刊名：FEBS Letters
• 出版年：2003
• 出版时间：May 8, 2003
• 年：2003
• 卷：542
• 期：1-3
• 页码：74-78
• 全文大小：165 K

文摘

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.