Department of Neonatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Maternal and Infant Health Research Institute and Medical College, Northwestern University, Xi'an, China.
Stress. 2021 Sep;24(5):612-620. doi: 10.1080/10253890.2021.1942829. Epub 2021 Jun 29.
Prenatal stress (PS) affects neurodevelopment and increases the risk for anxiety in adolescence in male offspring, but the mechanism is still unclear. N-Cadherin regulates the expression of AMPA receptors (AMPARs), which mediate anxiety by modulating network excitability in the prefrontal cortex (PFC). Our results revealed that in adolescent male, but not female, offspring rats, PS induced anxiety-like behavior, as assessed by the open field test (OFT). Furthermore, N-cadherin and AMPAR subunit GluA1 were colocalized in the PFC, and the expression of the N-cadherin and the GluA1 decreased following PS exposure in male offspring rats. We also found that the AMPAR agonist CX546 did not alleviate anxiety-like behavior in adolescent male offspring rats; however, it increased the expression of GluA1 in the PFC but did not alter the expression of N-cadherin. In conclusion, our study suggested that the N-cadherin-GluA1 pathway in the PFC mediates anxiety-like behavior in adolescent male offspring rats and that N-cadherin might be required for sex differences in the effect of PS on adolescent offspring.
产前应激（PS）会影响神经发育，并增加雄性后代青春期焦虑的风险，但具体机制尚不清楚。N-钙黏蛋白调节 AMPA 受体（AMPARs）的表达，通过调节前额叶皮层（PFC）的网络兴奋性来介导焦虑。我们的研究结果表明，在青春期雄性而非雌性后代大鼠中，PS 诱导了类似焦虑的行为，通过旷场试验（OFT）进行评估。此外，N-钙黏蛋白和 AMPAR 亚基 GluA1 在 PFC 中存在共定位，并且在雄性后代大鼠暴露于 PS 后，N-钙黏蛋白和 GluA1 的表达减少。我们还发现，AMPA 受体激动剂 CX546 不能缓解青春期雄性后代大鼠的类似焦虑行为；然而，它增加了 PFC 中 GluA1 的表达，但没有改变 N-钙黏蛋白的表达。总之，我们的研究表明，PFC 中的 N-钙黏蛋白-GluA1 通路介导了青春期雄性后代大鼠的类似焦虑行为，并且 N-钙黏蛋白可能是 PS 对青春期后代影响存在性别差异的原因。
