Valproic acid (VPA) is an anticonvulsant and one of the primary drugs used to treat bipolar mood disorder. It is also known to have teratogenetic side effects and to cause fetal valproate syndrome. VPA was recently found to be a direct inhibitor of histone deacetylase (HDAC). The hyperacetylation of histone induced by HDAC inhibitors causes anti-proliferation, thereby possibly affect developmental processes of brains. We previously found that VPA had opposing actions on the viability of immature and mature cerebellar granule cells (CGCs)(Kanai H et al., SFN abstract, 2002). VPA induced neurotoxicity in CGC cultures 0-4 days after plating, but was neuroprotective against excitotoxicity after more than 7 days in vitro (Kanai H et al., Pharmacogenomics J, 2004). This neurotoxic effect of VPA was concentration-dependent and correlated inversely with the age of the cultures. In this study, we hypothesized that HDAC inhibition of VPA causes neurotoxic effects in immature brains, and therefore explored VPA-induce...