Valproic acid, a mood stabilizer and anticonvulsant, protects rat cerebral cortical neurons from spontaneous cell death: a role of histone deacetylase inhibition.
(2003)
Journal - FEBS letters (Netherlands )
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.
| ISSN : | 0014-5793 |
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| Mesh Heading : | Aging Animals Anticonvulsants Antimanic Agents Cell Death Cells, Cultured Cerebral Cortex Dose-Response Relationship, Drug Enzyme Inhibitors Histone Deacetylases Neurons Neuroprotective Agents Rats Valproic Acid drug effects pharmacology cytology enzymology |
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| Mesh Heading Relevant : | pharmacology pharmacology cytology antagonists & inhibitors drug effects pharmacology pharmacology |
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