Intracellular Ca2+ signaling plays an essential role in synaptic plasticity. This study examined the effect of BPA on concentration of intracellular Ca2+ ([Ca2+]i) by measuring fluorescence intensity of Ca2+ in hippocampal neurons in vitro. The results showed that BPA for 30 min exerted dose-dependently dual effects on glutamate-elevated [Ca2+]i: BPA at 1-10 μM suppressed but at 1-100 nM enhanced glutamate-raised [Ca2+]i. BPA-potentiated [Ca2+]i was blocked by the antagonist of NMDA receptor and was eliminated by an estrogen-related receptor gamma (ERRγ) antagonist rather than an AR antagonist. Both inhibitors of MAPK/ERKs and MAPK/p38 blocked BPA-enhanced [Ca2+]i. Co-treatment of BPA with 17β-E2 or DHT eliminated the enhancement of 17β-E2, DHT, and BPA in glutamate-elevated [Ca2+]i. These results suggest that BPA at nanomole level rapidly enhances Ca2+ influx through NMDA receptor by ERRγ-mediated MAPK/ERKs and MAPK/p38 signaling pathways. However, BPA antagonizes both estrogen and androgen enhancing NMDA receptor-mediated Ca2+ influx in hippocampal neurons.
Keywords: Bisphenol-A; Hippocampal neuron; Intracellular Ca(2+); MAPK/ERKs; MAPK/p38.
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