The Rapid Effect Of Bisphenol-a On Long-Term Potentiation In The Hippocampus Of Young Rats

Background:Biphenol A (BPA), as a typical environmental endocrine disruptors (EEDs), has estrogenic and antiestrogenic dual functions. Synaptic plasticity plays a key role in the process of storing information during the formation of memory. Estrogen direct induces axon and dentron growth, synapse formation and plasticity maintenance, which relay on the neuroprotective role and neurotrophic effect induced by rapid activation of signaling molecule after the interaction between Estrogen and receptor on the membrane. BPA can affect synaptic structure and plasticity, but the mechanism is unclear. First, we study the effect of different concentrations of BPA on Long-term potentiation (LTP) Then, we investigate whether estrogen receptor (ER) Extracellular signal-regulated kinases (ERK) signaling participates in the effects of BPA on LTP, and explore the potential role of BPA on LTP.Methods:Electrophysiological techniques were used to record the field excitatory postsynaptic potential (fEPSP) and LTP of hippocampal dentate gyrus (DG). All experiments were carried on the transverse hippocampal slices of the Wistar rats (males, aged 4-5 weeks). The brains were rapidly removed after decapitation and placed in Artificial cerebro-spinal fluid (ACSF) saturated by mixture gas contained 95% oxygen and 5% carbon dioxide for 1 h, and continuously superfused in the recoding chamber at properly flowing speed and temperature. Hippocampal slices was perfused with 1,10,100,1000 nM BPA for 30 min before test stimulation (TS) (0.033 Hz). Two trains HFS (100 Hz) was applied to induced LTP. P-CLAMP 10.3 was used to analyze the recordings andcalculated the amplitude of LTP. To calculate the ratio of HFS after 60 min created the average amplitude by the EPSP and the initial slope of the EPSP by basis to stimulate in the 30 min, which to be the amplitude of LTP. The data were shown by the means±S.E.M. and in order to statistical comparison, we analyzed the date by one-way ANOVA.Results:1. Our results shown that BPA (1-1000 nM) dose-dependently decreased the peak value after HFS; but 100 nM BPA significantly enhances LTP, maintenance while 1000 nM BPA inhibits LTP maintenance.2. As one of Estrogen receptor blocking pharmacon, ICI 182,780 could block the LTP enhance induced by 100 nM BPA, pretreatment with U0126, a blocker of MEK1/2, LTP could not be induced after HFS, but BPA plus U0126 could inhibit the LTP enhance induced by BPA partly.3.100 nM BPA plus 10 nM 17β-E2 could completely inhibit the base EPSP enhance induced by E2 and decrease the LTP enhance induced by BPA after HFS.Conclusions:Our results suggest that BPA has dose-dependent dual functions on LTP of hippocampal DG, which mediated by ER/ERK signaling; however, antiestrogenic effect was observed in presence of BPA and estrogen.