Valproate administration to mice increases histone acetylation and 5-lipoxygenase content in the hippocampus.

Gene expression can be regulated by chromatin remodeling induced by the opposing actions of histone acetyltransferases and histone deacetylases (HDAC). HDAC inhibitors are considered putative anti-cancer drugs, but may also alter gene expression in the brain. Valproic acid (valproate; VPA), a drug used for treatment of bipolar disorder, has been characterized as a HDAC inhibitor. In neuronal cultures, VPA increases the expression of 5-lipoxygenase (5-LOX). Here we show that in vivo treatment of mice with intraperitoneal VPA injections increases the acetylation of histone H3 and the content of 5-LOX immunoreactive protein in the hippocampus. Since the extent of 5-LOX expression may alter mouse behavior, we suggest that VPA-altered chromatin remodeling and 5-LOX expression in the brain may be functionally important.