Effects of bisphenol-a on vasopressin regulating synaptic plasticity of hippocampus

The neuropeptide arginine vasopressin (AVP) plays an important role in the hippocampus by regulating neuronal excitability, synaptic plasticity, and other processes. Activity of AVP is regulated by sex hormones. The present study investigated the effects of bisphenol-A (BPA), a environmental endocrine disruptor, on AVP regulating synaptic plasticity of hippocamus. AVP at 10-100 nM significantly increased the dendrite complexity and dendrite spine density of hippocampal neurons in vitro, which was partially eliminated by AVP receptor 1a (V1aR) antagonist (RG7713) or oxytocin receptor (OTR) antagonist (L368-899). BPA at 10 nM increased neuronal dendritic complexity and spine density, which was partially eliminated by estrogen receptor (ERs) antagonist (ICI182,780) but completely abolished by antagonist of both ERs and ERRγ (Tamoxifen). BPA at 10 nM did not affect the effect of AVP (100 nM) on the dendrite complexity and spine density, but eliminated the promoting effects of DHT + AVP on the dendritic complexity. BPA at 1000 nM not only inhibited the dendritic complexity but also eliminated the promoting effects of AVP, 17β-estradiol (17β-E₂) + AVP, and 11-ketodihydrotestosterone (DHT) + AVP on the dendritic complexity. In addition, BPA at 1000 nM down-regulated the levels of V1aR and OTR protein expressions. Meanwhile, BPA at 10 nM promoted the maintenance of LTP of CA2 in the hippocampal slices, but co-treatment of BPA eliminated the effect of 17β-E₂ or DHT on LTP. BPA (10 nM) did not affect the promotion of long-term potentiation (LTP) by AVP, but eliminated the promotion of LTP by DHT + AVP. These results suggest that BPA at nanomoles levels affected AVP regulating modification of dendrite morphology and synaptic plasticity of hippocampus mainly by disrupting the effects of 17β-E₂ and/or DHT on AVP activity.