Perinatal exposure to bisphenol-A impairs learning-memory by concomitant down-regulation of N-methyl-D-aspartate receptors of hippocampus in male offspring mice.
ABSTRACT Bisphenol-A (BPA) has been shown to influence development of the brain and behaviors. The purpose of the present report was to investigate the effects of perinatal exposure to BPA on learning/memory and its mechanism of action, especially focusing on N-methyl-d-aspartate receptor (NMDAR). Perinatal maternal exposure to BPA at 0.5, 5, and 50mg/kg/d significantly extended the escape length to find the hidden platform in Morris water maze, and BPA at 0.5 or 5mg/kg/d markedly decreased the percentage of time spent in the quadrant where the platform had been during training both in postnatal day (PND) 21 and PND 56 mice. The results of passive avoidance test showed that the error frequency to step down from a platform after received footshock was significantly increased, and the latency of the step-down response onto the grid floor 24h after received footshock was obviously reduced by exposure to BPA at 5 and 50mg/kg/d (P<0.01) in the PND 21 offspring or at 50mg/kg/d in the PND 56 offspring (P<0.01). Furthermore, perinatal exposure to BPA significantly inhibited the expressions of NMDAR subunits NR1, NR2A, and 2B in the hippocampus during the development stage, especially in PND 56 mice. The expressions of estrogen receptor beta (ERbeta) in both PND 21 and PND 56 mice were markedly down-regulated by BPA at 0.5, 5, and 50mg/kg/d. These results indicate that perinatal exposure to BPA affects normal behavioral development in both spatial memory and avoidance memory, and also permanently influences the behavior of offspring in adulthood. The inhibition of expressions of NMDAR subunits and ERbeta in hippocampus during postnatal development stage may be involved.
Article: Bisphenol A depresses compound action potential of frog sciatic nerve in vitro involving Ca(2+)-dependent mechanisms.[show abstract] [hide abstract]
ABSTRACT: Bisphenol-A (BPA), a toxic chemical from polycarbonate plastics, is known for behavioural and neural abnormalities. These neuro-behavioural changes reflect the changes in neural activity. However the effect of BPA on nerve action potential is not available. Therefore, present investigation was undertaken to study the effect of BPA on compound action potential (CAP) of frog sciatic nerve. Bundle containing small group of nerve fibres in a sciatic nerve was dissected and placed in a Perspex chamber perfused with Ringer solution. Suction electrodes were applied to the cut ends of the nerve for stimulating and recording purposes. The stimulation of one end (with supramaximal strength) produced CAP in the recording electrode. BPA (1-100 μM) decreased the amplitude and repolarization time of CAP in a concentration-dependent manner, without any alteration in latency, rise time and threshold. The decrease in amplitude was directly correlated with decrease in repolarization time (r=0.76). The BPA-induced decreases were absent in Ca(2+)-free medium or in presence of L-type Ca(2+)-channel antagonist (nifedipine/deltiazem). T and P type Ca(2+) channel antagonist (Ni(2+)) failed to block the BPA-induced responses. Pre-treatment with an Erα antagonist (tamoxifen) blocked the BPA-induced decrease in CAP parameters. These observations indicate that the BPA decreased the amplitude and repolarization time of CAP involving L-type Ca(2+)-channel dependent mechanisms. Further involvement of Erα in the modulation of Ca(2+) channels is a possibility.Neuroscience Letters 04/2012; 517(2):128-32. · 2.11 Impact Factor
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ABSTRACT: Bisphenol A (BPA) is a man-made compound used to make polycarbonate plastics and epoxy resins; public health concerns have been fueled by findings that BPA exposure can reduce sex differences in brain and some behaviors. We asked if a low BPA dose, within the range measured in humans, ingested during pregnancy, would affect social behaviors in prepubertal mice. We noted sex differences in social interactions whereby females spent more time sitting side-by-side, while males engaged in more exploring and sitting alone. In addition BPA increased display of nose-to-nose contacts, play solicitations and approaches in both sexes. Interactions between sex and diet were found for self grooming, social interactions while sitting side-by-side and following the other mouse. In all these cases interactions were produced by differences between control and BPA females. We examined brains from embryos during late gestation to determine if gene expression differences might be correlated with some of the sexually dimorphic or BPA affected behaviors we observed. Because BPA treatments ended at birth we took the brains during embryogenesis to increase the probability of discovering BPA mediated effects. We also selected this embryonic age (E18.5) because it coincides with the onset of sexual differentiation of the brain. Interestingly, mRNA for the glutamate transporter, Slc1a1, was enhanced by exposure to BPA in female brains. Also we noted that BPA changed the expression of two of the three DNA methyltransferase genes, Dnmt1 and Dnmt3a. We propose that BPA affects DNA methylation of Sc1a1 during neural development. Sex differences in juvenile social interactions are affected by BPA and in particular this compound modifies behavior in females.PLoS ONE 01/2011; 6(9):e25448. · 4.09 Impact Factor