Bisphenol A exposure remodels cognition of male rats attributable to excitatory alterations in the hippocampus and visual cortex

Abstract

Bisphenol A, an environmental xenoestrogen, has been shown sex-specific adverse effects on cognitive function of rodents. However, the specific mechanisms underlying these outcomes remain elusive, limiting our understanding the differences in behavioral impairments due to BPA exposure between genders in humans. The present study chose the juvenile stage (with a stable estrogen level) as the exposure window to explore BPA effects on cognitive behaviors of male and female Sprague-Dawley (SD) rats and related mechanisms. Three dosages of BPA (0.04, 0.4 and 4 mg/kg/day) were chose to make BPA-exposed models. Especially, the mid-dose for rats was close to the current reference daily limit for human exposure given by the U.S. Environmental Protection Agency. Our results showed that male but not female juvenile rats had a marked decline in spatial memory after 0.4 mg/kg/day BPA exposure, which accompanied with downregulation of glutamate receptor (NR2) expression in their hippocampus and primary visual cortex (V1). In the high-dose BPA exposed groups (4 mg/kg/day), there was not only a deficit of spatial memory, but also an anxiety-like behavior of male rats. Additionally, those rats had a significant decline in spine density of pyramidal neurons and a decreased expression of glutamate receptor subtypes (NR2 and GluR1) in the hippocampus. Importantly, such impairments in the hippocampus of male rats were associated with a decrease of glutamate receptor (NR2) expression in the V1, which could perturb the visual information inputs. To some extent, altered ERβ expression within their hypothalamus could contribute to the anxiety-like behavior after high-dose BPA exposure. However, the low-dose BPA exposed juvenile rats didn't present any structural and behavioral changes in our present study. Those results suggests that BPA exerts dose dependent and gender-specific effects on the cognition of juvenile animals. Our findings shed light on mechanisms underlying BPA effects on the juvenile animals.

Keywords: Bisphenol A; Hippocampus; Hypothalamus; Primary visual cortex (V1); Spatial memory.