Gender-Dependent Actions of the Histone Deacetylase Blocker Sodium Valproate on Olfactory Learning in 129Sv Mice during the Early Postnatal Period

Abstract

The processes of histone acetylation in the brain underlie both the mechanisms supporting the long-term stable effects of early experience, transmitted to offspring generations by epigenetic inheritance, and learning. However, the role of acetylation in learning has previously been studied only in adult animals: high levels of learning can be linked with high levels of histone H3 acetylation in the brain. The role of acetylation processes in the mechanisms of early learning has not been addressed. We report here our studies of the effects of blockade of histone deacetylation with sodium valproate, which increases the level of acetylation of histone H3, on the outcome of training to olfactory discrimination in 8-day-old mice of strain 129Sv, which have low levels of learning with simulation of maternal grooming. Four doses of sodium valproate, given from day 3 to day 6 of postnatal development, were found to have gender-dependent actions: there were selective improvements in learning in males but not females, though females showed this seen after repeated administration of physiological saline. The possible epigenetic mechanisms underlying these gender-related differences are discussed.