Department of Occupational and Environmental Health, School of Public Health, China Medical University, PR China.
Department of Occupational and Environmental Health, School of Public Health, China Medical University, PR China.
Brain Res Bull. 2019 Mar;146:270-278. doi: 10.1016/j.brainresbull.2019.01.014. Epub 2019 Jan 17.
Nonylphenol (NP), a global environmental pollutant, has been found to result in impairments of neurodevelopment. However, effects of maternal exposure to NP on learning and memory and the potential mechanisms are largely unexplored. Thus, we treated dams with NP during gestation and lactation to study its effect on learning and memory in offspring. Morris water maze (MWM) task and the electrophysiological recording in the hippocampus were conducted in pups. We also investigated the activation of BDNF-PI3K/Akt signaling and the expression of its target protein PSD-95 in offspring hippocampus, which are curial for the synaptic plasticity and learning and memory. The results showed that maternal exposure to NP led to poor performance in MWM task and especially impairments of long-term potentiation (LTP), although the termination of NP exposure was at the end of lactation. Meanwhile, maternal exposure to NP also decreased the activation of BDNF-PI3K/Akt signaling and the protein level of PSD-95. Taken together, our results support the hypothesis that maternal exposure to NP during gestation and lactation causes damages to learning and memory. In addition, suppressed activation of the BDNF-PI3K/Akt signaling may contribute to these impairments caused by maternal exposure to NP.
壬基酚(NP)是一种全球性的环境污染物,已被发现会导致神经发育受损。然而,母体暴露于 NP 对学习和记忆的影响及其潜在机制在很大程度上尚未得到探索。因此,我们在妊娠和哺乳期用 NP 处理母鼠,以研究其对子代学习和记忆的影响。在幼鼠中进行了 Morris 水迷宫(MWM)任务和海马电生理记录。我们还研究了 NP 暴露后子代海马中脑源性神经营养因子(BDNF)-PI3K/Akt 信号的激活及其靶蛋白 PSD-95 的表达,这对于突触可塑性和学习记忆至关重要。结果表明,母体暴露于 NP 导致 MWM 任务表现不佳,特别是长时程增强(LTP)受损,尽管 NP 暴露的终止时间是哺乳期结束时。同时,母体暴露于 NP 还降低了 BDNF-PI3K/Akt 信号的激活和 PSD-95 的蛋白水平。综上所述,我们的结果支持了母体在妊娠和哺乳期暴露于 NP 会导致学习和记忆受损的假设。此外,BDNF-PI3K/Akt 信号的激活受到抑制可能导致 NP 暴露引起的这些损伤。