Exposure to bisphenol-A affects fear memory and histone acetylation of the hippocampus in adult mice

Bisphenol-A (BPA), an environmental endocrine disruptor, has been reported to possess weak estrogenic, anti-estrogenic, and anti-androgen properties. Previous evidence indicates that perinatal exposure to low levels of BPA affects anxiety-like and cognitive behaviors in adult rodents. The present study aims to investigate the effect of BPA on emotional memory using the contextual fear conditioning of male mice in adulthood exposed to BPA for 90 days. The results indicated that exposure to BPA increased the freezing time 1 h and 24 h after fear conditioning training. Furthermore, western blot analyses showed that BPA exposure decreased the level of N-methyl-d-aspartic acid (NMDA) receptor subunit NR1 and increased the expression of histone deacetylase 2 (HDAC2) before fear conditioning training in the hippocampus of male mice. One and twenty-four hours after fear conditioning training, BPA enhanced the changes of the expressions of NR1, phosphorylated extracellular regulated protein kinases (ERK1/2), and histone acetylation induced by contextual fear conditioning in the hippocampus. These results suggest that long term exposure to BPA enhanced fear memory by the concomitant increased level of NMDA receptor and/or the enhanced histone acetylation in the hippocampus, which may be associated with activation of ERK1/2 signaling pathway.