Abstract:

Bisphenol-A (BPA), an environmental endocrine disruptor used in the production of plastics, has been reported to possess weakly estrogenic and anti-androgenic properties. The present study aims to investigate the effect of BPA on fear memory of male mice exposed to BPA in adulthood. Nine-week-old male mice were orally exposed (ig) to BPA (0.4, 4, or 40 mg/kg/d) for 90d, and then received contextual fear conditioning test. The total time of freezing was measured 1 h and 24 h after training. At the same time, the hippocampus of mice before or 1 hr, 24 hr after fear conditioning training were dissociated for western blot analyses. The results showed that adulthood exposure to BPA (4 and/or 40 mg/kg/d) increased the freezing time 1 hr and 24 hr 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. One and 24 hr after fear conditioning training, BPA enhanced the increases of the levels of NR1, histone acetylation, and extracellular regulated protein kinases (ERK1/2) phosphorylation in hippocampus induced by fear conditioning training. These results suggest that long term exposure to BPA enhanced acquisition and retention of fear memory by concomitant the increases of histone acetylation and the level of NMDA receptor which may be associated with activation of ERK1/2 signaling pathway.

Key words: bisphenol-A, contextual fear conditioning, histone acetylation, extracellular regulated protein kinases (ERKs)