Effects of Early-Life Stress and HDAC Inhibition on Maternal Behavior in Mice

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Despite the well-established fact that maternal care plays a pivotal role in the offspring development, little is known about the effects of disruption of maternal care early in life on the development of this behavior in the offspring. Using brief repeated maternal separation (45 min/day on postnatal Days 3–6), which represents a model of early life stress, we found behavioral changes in adult female mice offspring. The decrease in home cage exploratory behavior (both pup-directed and nonpup-directed) was revealed later in adulthood without changes in maternal care level. Maternal separation coupled with pain exposure caused by subcutaneous saline injection procedure had a cumulative resulting effect, which was manifested in the decreased level of nursing associated with licking-grooming in adult females. The behavioral changes found in adult female offspring could be triggered by identified changes in the behavior of their mothers, while alterations of the level of histone H3 acetylation in the neonatal brain were not detected. Histone deacetylase inhibitor sodium valproate was used in order to study the possibility of preventing the effects of early life stress through involvement of epigenetic mechanisms. Despite the increase in the level of histone H3 acetylation in the neonatal brain caused by valproate, its behavioral effects were barely detectable. These effects were reflected in prevention of the reduction of nursing associated with licking-grooming induced by maternal separation, accompanied by pain exposure. The data are discussed in terms of the possible application to the studies of mechanisms underlying long-term effects of human early life trauma.

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