Inhibition of c-Jun in AgRP neurons increases stress-induced anxiety and colitis susceptibility.
Inhibition of c-Jun in AgRP neurons increases stress-induced anxiety and colitis susceptibility.
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AgRP 神经元中 c-Jun 的抑制会增加应激引起的焦虑和结肠炎易感性。
DOI：
10.1038/s42003-023-04425-w
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发表时间：
2023-01-14
影响因子：
5.9
通讯作者：
Guo, Feifan
中科院分区：
文献类型：
--
作者：
Jiao, Fuxin;Hu, Xiaoming;Yin, Hanrui;Yuan, Feixiang;Zhou, Ziheng;Wu, Wei;Chen, Shanghai;Liu, Zhanju;Guo, Feifan
精神疾病，如焦虑，与炎症性肠病（IBD）有关，然而，调节这种共病的神经机制尚不清楚。在这里，我们发现下丘脑刺痛相关蛋白（AgRP）神经元活动在慢性约束应激（CRS）下被抑制，这种情况已知会增加焦虑和结肠炎的易感性。一致地，AgRP神经元的化学激活或抑制分别逆转或模仿crs诱导的焦虑样行为和结肠炎易感性的增加。此外，CRS通过抑制c-Jun的表达来抑制AgRP神经元的活性。此外，这些神经元中c-Jun的过表达可保护crs诱导的效应，而AgRP神经元中c-Jun的下调（c-Jun∆AgRP）可促进焦虑和结肠炎易感性。最后，分泌蛋白血栓反应蛋白1 （THBS1）的水平与焦虑和结肠炎的增加呈负相关，补充重组THBS1可以缓解c-Jun∆AgRP小鼠的结肠炎易感性。综上所述，这些结果揭示了下丘脑AgRP神经元衍生的c-Jun在协调应激性焦虑和结肠炎易感性中的关键作用。慢性约束应激诱导焦虑样行为和结肠炎易感性，这是由AgRP神经元c-Jun介导的。
Psychiatric disorders, such as anxiety, are associated with inflammatory bowel disease (IBD), however, the neural mechanisms regulating this comorbidity are unknown. Here, we show that hypothalamic agouti-related protein (AgRP) neuronal activity is suppressed under chronic restraint stress (CRS), a condition known to increase anxiety and colitis susceptibility. Consistently, chemogenic activation or inhibition of AgRP neurons reverses or mimics CRS-induced increase of anxiety-like behaviors and colitis susceptibility, respectively. Furthermore, CRS inhibits AgRP neuronal activity by suppressing the expression of c-Jun. Moreover, overexpression of c-Jun in these neurons protects against the CRS-induced effects, and knockdown of c-Jun in AgRP neurons (c-Jun∆AgRP) promotes anxiety and colitis susceptibility. Finally, the levels of secreted protein thrombospondin 1 (THBS1) are negatively associated with increased anxiety and colitis, and supplementing recombinant THBS1 rescues colitis susceptibility in c-Jun∆AgRP mice. Taken together, these results reveal critical roles of hypothalamic AgRP neuron-derived c-Jun in orchestrating stress-induced anxiety and colitis susceptibility. Chronic restraint stress induces anxiety-like behaviors and colitis susceptibility, which is mediated by c-Jun in AgRP neurons.
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影响因子：
16.2
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