Bisphenol-A Antagonizes the Rapidly Modulating Effect of Dihydrotestosterone on Spinogenesis and Long-Term Potentiation of Hippocampal Neurons

In the 2018 study, researchers found that Bisphenol-A (BPA) rapidly increased dendritic spine and synapse densities in cultured hippocampal neurons of rats at concentrations of 10-100 nM, and this effect was antagonistic to dihydrotestosterone (DHT). BPA's enhancements were blocked by an estrogen receptor antagonist, indicating action through estrogen receptors, and were dependent on ERK1/2 and p38 MAPK pathways. BPA also enhanced long-term potentiation (LTP) in hippocampal slices from younger male rats, an effect not blocked by an androgen receptor antagonist but inhibited by a p38 MAPK inhibitor. The study concluded that BPA can promote spinogenesis and synaptic activity through estrogen receptors and involves ERKs and p38 signaling pathways, while antagonizing the effects of DHT on synaptic plasticity.