Engineering Research Center of Bio-process, Ministry of Education, Hefei University of Technology, 193 Tunxi Road, Hefei, Anhui 230009, PR China; School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui 230009, PR China.
School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui 230009, PR China.
Toxicol Appl Pharmacol. 2021 Sep 1;426:115641. doi: 10.1016/j.taap.2021.115641. Epub 2021 Jul 7.
Bisphenol-A (BPA) is an environmental endocrine disruptor and impairs learning and memory. However, the direct evidence for BPA exposure affecting neural circuits has been limited. In this study, a virus tracing assay has been established to explore the brain's neural circuits. Thy1-Cre mice were used to investigate the effects of BPA on the neural projection of glutamatergic pyramidal neurons in hippocampal CA1 based on Thy1 promoter. These transgenic mice were orally exposed to BPA (0, 0.5 mg/kg/day) from postnatal day (PND) 0 to PND60 and then subjected to behavioral tests. Morris water maze(MWM)and Barnes maze's showed that the spatial memory was seriously impaired in BPA exposed Thy1-Cre mice. Virus tracing assay indicated that CA1 pyramidal neurons mainly received neural inputs from hippocampal CA3, entorhinal cortex (EC), and medial septum (MS). The analysis showed that BPA reduced the number of RV neurons in CA3 and EC but not MS. The immunohistochemistry experiment displayed that BPA decreased the percentage of CaMKII cells in CA3 and EC. The results demonstrated that the synaptic connection of upstream glutamatergic neurons and CA1 pyramidal cells was weakened by BPA exposure. These point to potentially detrimental effects of BPA exposure on the excitatory neural circuit of CA3-CA1 and EC-CA1 in memory formation. Thus, our findings revealed that the decrease in excitatory neural circuits of CA3-CA1 and EC-CA1 contribute to the BPA-induced spatial memory deficits in Thy1-Cre mice.
双酚 A（BPA）是一种环境内分泌干扰物，会损害学习和记忆。然而，BPA 暴露影响神经回路的确切证据一直有限。在这项研究中，建立了一种病毒追踪测定法来探索大脑的神经回路。使用 Thy1-Cre 小鼠，基于 Thy1 启动子，研究 BPA 对海马 CA1 区谷氨酸能锥体神经元神经投射的影响。这些转基因小鼠从出生后第 0 天（PND）到 PND60 每天经口暴露于 BPA（0、0.5mg/kg/天），然后进行行为测试。Morris 水迷宫（MWM）和 Barnes 迷宫实验表明，BPA 暴露的 Thy1-Cre 小鼠的空间记忆严重受损。病毒追踪测定表明，CA1 锥体神经元主要接收来自海马 CA3、内嗅皮层（EC）和中隔（MS）的神经输入。分析表明，BPA 减少了 CA3 和 EC 中的 RV 神经元数量，但对 MS 没有影响。免疫组织化学实验显示，BPA 减少了 CA3 和 EC 中的 CaMKII 细胞的百分比。结果表明，BPA 暴露削弱了上游谷氨酸能神经元和 CA1 锥体细胞之间的突触连接。这些结果表明，BPA 暴露对 CA3-CA1 和 EC-CA1 兴奋性神经回路可能产生有害影响，从而导致 Thy1-Cre 小鼠空间记忆缺陷。因此，我们的研究结果表明，CA3-CA1 和 EC-CA1 兴奋性神经回路的减少导致了 Thy1-Cre 小鼠的 BPA 诱导的空间记忆缺陷。
