| Autor: |
Jeong, Mi Ra, Hashimoto, Ryota, Senatorov, Vladimir V., Fujimaki, Koichiro, Ren, Ming, Lee, Min Soo, Chuang, De-Maw |
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| Zdroj: |
FEBS Letters; May2003, Vol. 542 Issue 1-3, p74, 5p |
| Abstrakt: |
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. [Copyright &y& Elsevier] |
| Databáze: |
Complementary Index |
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