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The effects of low molar concentrations of bisphenol A on neuron viability and survival under neurotoxic stress Tong, Jade Pui Wai


Bisphenol A (BPA) is an ubiquitous environmental xenoestrogen excreted in the urine of 95-99\% of humans studied. In this investigation, we examine the effects of 1mM to 10fM concentrations of BPA on the viability of rat cortical neurons under acute (5h) and chronic (DIV3-9, DIV3-15) exposure conditions. Post-exposure, we also challenged the cultures with an oxidative or excitotoxic stress to determine whether BPA conferred neuroprotection, susceptibility or neither to the challenged cultures. Finally, we studied the effects of different concentrations of BPA on the activation of SREBP~1, a transcription factor that regulates many genes with important effects on neuron function. We found that 1mM and 500uM BPA are neurotoxic under chronic exposure, but only 1mM BPA decreased cell viability after 5h. Acute and chronic exposure to BPA conferred neither neuroprotection nor susceptibility to oxidative or excitotoxic stress in the neuron cultures. Five hours exposure to 10pM and 1pM BPA increased SREBP~1 activation two-fold. In DIV9 cultures, 10pM BPA stimulated a maximal three-fold SREBP~1 activation at 8h post exposure, while at DIV15, 10pM BPA stimulated a maximal two-fold SREBP~1 activation at 5h post exposure. High, physiologically irrelevant concentrations of BPA induce neuronal cell death, and while sublethal concentrations do not predispose cultures to oxidative or excitotoxic stress, they also do not confer neuroprotection as a true estrogen, estradiol, would. Sublethal concentrations of BPA activate SREBP~1 in a hormetic manner, resulting in a non-monotonic dose response curve.

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