Sex-specific effects of bisphenol-A on memory and synaptic structural modification in hippocampus of adult mice

Humans are routinely exposed to low levels of bisphenol A (BPA), a synthetic xenoestrogen widely used in the production of polycarbonate plastics. The effects of long-term exposure to BPA on memory and modification of synaptic structure in hippocampus of adult mice were investigated in the present study. The adult mice were exposed to BPA (0.4, 4, and 40 mg/kg/day) or arachis oil for 12 weeks. In open field test, BPA at 0.4, 4, or 40 mg/kg/day increased the frequency of rearing and time in the central area of the males, while BPA at 0.4 mg/kg/day reduced the frequency of rearing in the females. Exposure to BPA (0.4 or 40 mg/kg/day) extended the average escape pathlength to the hidden platform in Morris water maze task and shortened the step-down latency 24 h after footshock of the males, but no changes were found in the females for these measures. Meanwhile, BPA induced a reduced numeric synaptic density and a negative effect on the structural parameters of synaptic interface, including an enlarged synaptic cleft and the reduced length of active zone and PSD thickness, in the hippocampus of the male mice. Western blot analyses further indicated that BPA down-regulated expressions of synaptic proteins (synapsin I and PSD-95) and synaptic NMDA receptor subunit NR1 and AMPA receptor subunit GluR1 in the hippocampus of the males. These results suggest that long-term exposure to low levels of BPA in adulthood sex-specifically impaired spatial and passive avoidance memory of mice. These effects may be associated with the higher susceptibility of the hippocampal synaptic plasticity processes, such as remodeling of spinal synapses and the expressions of synaptic proteins (e.g. synapsin I and PSD-95) and NMDA and AMPA receptors, to BPA in the adult male mice.