Abstract
Bisphenol-A (BPA, 4, 4′-isopropylidene-2-diphenol), a synthetic xenoestrogen that widely used in the production of polycarbonate plastics, has been reported to impair hippocampal development and function. Our previous study has shown that BPA exposure impairs Sprague-Dawley (SD) male hippocampal dendritic spine outgrowth. In this study, the sex-effect of chronic BPA exposure on spatial memory in SD male and female rats and the related synaptic mechanism were further investigated. We found that chronic BPA exposure impaired spatial memory in both SD male and female rats, suggesting a dysfunction of hippocampus without gender-specific effect. Further investigation indicated that BPA exposure causes significant impairment of dendrite and spine structure, manifested as decreased dendritic complexity, dendritic spine density and percentage of mushroom shaped spines in hippocampal CA1 and dentate gyrus (DG) neurons. Furthermore, a significant reduction in Arc expression was detected upon BPA exposure. Strikingly, BPA exposure significantly increased the mIPSC amplitude without altering the mEPSC amplitude or frequency, accompanied by increased GABAARβ2/3 on postsynaptic membrane in cultured CA1 neurons. In summary, our study indicated that Arc, together with the increased surface GABAARβ2/3, contributed to BPA induced spatial memory deficits, providing a novel molecular basis for BPA achieved brain impairment.
Highlights
Gonadal steroid hormones play pivotal roles in brain development and this influence persists and can even determine behavior patterns throughout life[1,2]
Morris water maze (MWM) test was employed to assay the effect of BPA on spatial memory in SD rats
We found that BPA exposure significantly increased the postsynaptic abundance of GABAA receptor (GABAAR), manifested as increased surface GABAARβ2/3 integrated puncta intensity (Fig. 8B, Control, 0.91 ± 0.02; BPA, 1.12 ± 0.08) assessed by immunofluorescence experiments
Summary
Gonadal steroid hormones play pivotal roles in brain development and this influence persists and can even determine behavior patterns throughout life[1,2]. BPA may exert different effects on male and female rats due to the complicated internal environment, such as different hormone level, hormone type and metabolic rate of BPA. Emerging evidence provided by behavioral studies has linked BPA exposure with memory deficits, but the mechanism still remains elusive. Our previous work has suggested a link between dendritic spine and spatial memory in SD male rats[4]. BPA has long been implicated in the impairment of spine formation and cognition, while whether it functions through Arc has not been reported yet. This study, for the first time, systematically investigated the relationship between BPA induced spatial memory deficits and dendritic development, spine morphology and synaptic transmission, providing novel molecular mechanism for BPA induced cognition deficits
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