Valproic Acid, a Mood Stabilizer and Anticonvulsant, Protects Rat
FEBS Letters 542 (2003) 74^78 FEBS 27183 View metadata, citation and similar papers at core.ac.uk brought to you by CORE Valproic acid, a mood stabilizer and anticonvulsant, protects ratprovided cerebralby Elsevier - Publisher Connector cortical neurons from spontaneous cell death: a role of histone deacetylase inhibition Mi Ra Jeonga, Ryota Hashimotoa, Vladimir V. Senatorova, Koichiro Fujimakia, Ming Rena, Min Soo Leeb, De-Maw Chuanga;Ã aMolecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, Bldg. 10, Rm. 4C-206, 10 Center Dr MSC 1363, Bethesda, MD 20892-1363, USA bDepartment of Psychiatry, College of Medicine, Korea University, Seoul 136-701, South Korea Received 15 March 2003; revised 27 March 2003; accepted 28 March 2003 First published online 11 April 2003 Edited by Jesus Avila phylaxis for both manic and depressive phases of this mood Abstract We studied the neuroprotective e¡ects of valproic acid (VPA), a primary mood stabilizer and anticonvulsant, in disorder. Despite intensive research, the mechanisms under- cultured rat cerebral cortical neurons (CCNs). CCNs underwent lying the therapeutic e¡ects of VPA remain obscure. Since spontaneous cell death when their age increased in culture. As clinical e⁄cacy for VPA requires chronic treatment, it has shown by mitochondrial activity and calcein-AM assays, treat- been postulated that drug-induced changes in gene expression ment of CCNs with VPA starting from day 9 in vitro markedly are required for its therapeutic actions [3]. Recently, VPA was increased viability and prolonged the life span of the cultures. reported to directly inhibit histone deacetylase (HDAC) at The neuroprotective action of VPA was time-dependent and therapeutic levels (with an IC50 = 0.4 mM), causing histone occurred at therapeutic levels with a maximal e¡ect at about hyperacetylation [4,5].
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