Medicine College, Henan University of Chinese Medicine, Zhengzhou, China.
Medicine College, Henan University of Chinese Medicine, Zhengzhou, China.
Behav Brain Res. 2023 Sep 13;453:114598. doi: 10.1016/j.bbr.2023.114598. Epub 2023 Jul 26.
Mental disorders (MD), such as anxiety, depression, and cognitive impairment, are very common during pregnancy and predispose to adverse pregnancy outcomes; however, the underlying mechanisms are still under intense investigation. Although the most common RNA modification in epigenetics, N-methyladenosine (mA) has been widely studied, its role in MD has not been investigated. Here, we observed that fat mass and obesity-associated protein (FTO) are downregulated in the hippocampus of pregnant rats with MD induced by fear stress and demonstrated that FTO participates in and regulates MD induced by fear stress. In addition, we identified four genes with anomalous modifications and expression (double aberrant genes) that were directly regulated by FTO, namely Angpt2, Fgf10, Rpl21, and Adcy7. Furthermore, we found that these genes might induce MD by regulating the PI3K/Akt and Rap1 signaling pathways. It appears that FTO-mediated mA modification is a key regulatory mechanism in MD caused by fear stress during pregnancy.
精神障碍（MD），如焦虑、抑郁和认知障碍，在怀孕期间非常常见，并且容易导致不良的妊娠结局；然而，其潜在的机制仍在深入研究中。尽管最常见的 RNA 修饰在表观遗传学中，N6-甲基腺苷（m6A）已被广泛研究，但它在 MD 中的作用尚未被研究。在这里，我们观察到在由恐惧应激引起的 MD 的孕鼠海马体中，肥胖相关蛋白（FTO）下调，并表明 FTO 参与并调节由恐惧应激引起的 MD。此外，我们鉴定了四个具有异常修饰和表达（双异常基因）的基因，它们被 FTO 直接调控，即 Angpt2、Fgf10、Rpl21 和 Adcy7。此外，我们发现这些基因可能通过调节 PI3K/Akt 和 Rap1 信号通路来诱导 MD。似乎 FTO 介导的 m6A 修饰是妊娠期间恐惧应激引起的 MD 的关键调节机制。
