He Xiaoman, Li Yuhang, Zhang Nana, Huang Jinfang, Ming Xing, Guo Ruixiao, Hu Yang, Ji Pengfei, Guo Feifei
Pathophysiology Department, School of Basic Medicine, Qingdao University, Qingdao, China.
Department of Clinical Laboratory, the Affiliated Hospital of Qingdao University, Qingdao, China.
Front Pharmacol. 2022 Aug 9;13:906057. doi: 10.3389/fphar.2022.906057. eCollection 2022.
The limbic system plays a pivotal role in stress-induced anxiety and intestinal disorders, but how the functional circuits between nuclei within the limbic system are engaged in the processing is still unclear. In our study, the results of fluorescence gold retrograde tracing and fluorescence immunohistochemistry showed that the melanin-concentrating hormone (MCH) neurons of the lateral hypothalamic area (LHA) projected to the basolateral amygdala (BLA). Both chemogenetic activation of MCH neurons and microinjection of MCH into the BLA induced anxiety disorder in mice, which were reversed by intra-BLA microinjection of MCH receptor 1 (MCHR1) blocker SNAP-94847. In the chronic acute combining stress (CACS) stimulated mice, SNAP94847 administrated in the BLA ameliorated anxiety-like behaviors and improved intestinal dysfunction via reducing intestinal permeability and inflammation. In conclusion, MCHergic circuit from the LHA to the BLA participates in the regulation of anxiety-like behavior in mice, and this neural pathway is related to the intestinal dysfunction in CACS mice by regulating intestinal permeability and inflammation.
边缘系统在应激诱导的焦虑和肠道疾病中起关键作用,但边缘系统内核团之间的功能回路如何参与这一过程仍不清楚。在我们的研究中,荧光金逆行追踪和荧光免疫组织化学结果显示,下丘脑外侧区(LHA)的促黑素细胞激素(MCH)神经元投射到杏仁核基底外侧核(BLA)。MCH神经元的化学遗传学激活和向BLA内微量注射MCH均诱导小鼠出现焦虑症,而向BLA内微量注射MCH受体1(MCHR1)阻断剂SNAP-94847可逆转这一现象。在慢性急性联合应激(CACS)刺激的小鼠中,向BLA注射SNAP94847可改善焦虑样行为,并通过降低肠道通透性和炎症来改善肠道功能障碍。总之,从LHA到BLA的MCH能回路参与调节小鼠的焦虑样行为,并且该神经通路通过调节肠道通透性和炎症与CACS小鼠的肠道功能障碍有关。