Kumar Dhiraj, Thakur M K
Biochemistry and Molecular Biology Laboratory, Centre of Advanced Study, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005, India.
Biochemistry and Molecular Biology Laboratory, Centre of Advanced Study, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005, India.
Toxicology. 2017 Mar 1;378:107-113. doi: 10.1016/j.tox.2017.01.010. Epub 2017 Jan 13.
Bisphenol-A (BPA) is a synthetic endocrine disruptor which causes anxiety like behavior in rodents, though the underlying mechanism is not clearly understood. As excitatory-inhibitory synaptic proteins are the key regulators of anxiety, we have examined the effect of perinatal exposure to BPA on this behavior and the expression of excitatory (PSD95), inhibitory (gephyrin) and presynaptic density marker (synaptophysin) proteins in cerebral cortex and hippocampus of 3 and 8 weeks postnatal male mice. In open field (OF) test, BPA exposure reduced the time spent, number of entries and distance travelled in the central zone as compared to control in 8 weeks mice. On the other hand, elevated plus maze (EPM) results showed decrease in time spent and number of entries to the open arms. Immunoblotting and immunofluorescence analysis showed significant downregulation of PSD95 and synaptophysin, but upregulation of gephyrin, leading to reduction in excitatory to inhibitory protein ratio and synaptic density in postnatal 3 and 8 weeks mice. Thus, our findings show that the anxiety like behavior due to perinatal exposure to BPA is associated with decrease in excitatory to inhibitory synaptic density in postnatal male mice.
双酚A(BPA)是一种合成内分泌干扰物,可导致啮齿动物出现类似焦虑的行为,但其潜在机制尚不清楚。由于兴奋性-抑制性突触蛋白是焦虑的关键调节因子,我们研究了围产期暴露于双酚A对出生后3周和8周雄性小鼠的这种行为以及大脑皮层和海马中兴奋性(PSD95)、抑制性(gephyrin)和突触前密度标记物(突触素)蛋白表达的影响。在旷场(OF)试验中,与8周龄对照小鼠相比,暴露于双酚A的小鼠在中央区域花费的时间、进入次数和移动距离减少。另一方面,高架十字迷宫(EPM)结果显示,在开放臂上花费的时间和进入次数减少。免疫印迹和免疫荧光分析显示,PSD95和突触素显著下调,但gephyrin上调,导致出生后3周和8周小鼠的兴奋性与抑制性蛋白比率和突触密度降低。因此,我们的研究结果表明,围产期暴露于双酚A引起的类似焦虑行为与出生后雄性小鼠兴奋性到抑制性突触密度降低有关。