Wang Chong, Niu Ruiyan, Zhu Yuchen, Han Haijun, Luo Guangying, Zhou Bingrui, Wang Jundong
Shanxi Key Laboratory of Ecological Animal Science and Environmental Medicine, Shanxi Agricultural University, PR China.
Shanxi Key Laboratory of Ecological Animal Science and Environmental Medicine, Shanxi Agricultural University, PR China.
Toxicology. 2014 Aug 1;322:51-60. doi: 10.1016/j.tox.2014.05.001. Epub 2014 May 10.
Bisphenol A (BPA), a component of polycarbonate and epoxy resins, has been reported to adversely impact the central nervous system, especially with respect to learning and memory. However, the precise effect and specific mechanisms have not been fully elucidated. In the present study, pregnant Sprague-Dawley rats were orally administered with BPA at 0.05, 0.5, 5 or 50mg/kg·body weight (BW) per day from embryonic day 9 (E 9) to E 20. We examined the effects of maternal BPA exposure on memory and synaptic structure in the hippocampus of male offspring at postnatal day (PND) 21. Maternal BPA exposure significantly affected locomotor activity, exploratory habits, and emotional behavior in open field test, and increased reference and especially working memory errors in the radial arm maze during the postnatal developing stage. Maternal BPA exposure had an adverse effect on synaptic structure, including a widened synaptic cleft, a thinned postsynaptic density (PSD), unclear synaptic surface and disappeared synaptic vesicles. Furthermore, maternal BPA exposure decreased the mRNA and protein expressions of synaptophysin, PSD-95, spinophilin, GluR1 and NMDAR1 in the hippocampus of male offspring on PND 21. These results showed that fetal growth and development was more sensitive to BPA exposure. The decreased learning and memory induced by maternal exposure to BPA in this study may be involved in synaptic plasticity alteration.
双酚A(BPA)是聚碳酸酯和环氧树脂的一种成分,据报道会对中枢神经系统产生不利影响,尤其是在学习和记忆方面。然而,其确切作用和具体机制尚未完全阐明。在本研究中,从胚胎第9天(E9)至E20,每天给怀孕的斯普拉格-道利大鼠口服0.05、0.5、5或50mg/kg体重(BW)的双酚A。我们检测了母体双酚A暴露对出生后第21天(PND)雄性子代海马体中记忆和突触结构的影响。母体双酚A暴露显著影响旷场试验中的运动活动、探索习惯和情绪行为,并在出生后发育阶段增加了放射状臂迷宫中的参考记忆尤其是工作记忆错误。母体双酚A暴露对突触结构有不利影响,包括突触间隙增宽、突触后致密物(PSD)变薄、突触表面不清晰和突触小泡消失。此外,母体双酚A暴露降低了出生后第21天雄性子代海马体中突触素、PSD-95、亲棘蛋白、GluR1和NMDAR1的mRNA和蛋白表达。这些结果表明,胎儿生长发育对双酚A暴露更为敏感。本研究中母体暴露于双酚A所致的学习和记忆下降可能与突触可塑性改变有关。