2. Academic Validation
  3. 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

  • Commun Biol. 2023 Jan 14;6(1):50. doi: 10.1038/s42003-023-04425-w.
Fuxin Jiao 1 2,  Xiaoming Hu 1,  Hanrui Yin 2,  Feixiang Yuan 1,  Ziheng Zhou 2,  Wei Wu 3,  Shanghai Chen 1,  Zhanju Liu 4,  Feifan Guo 5
Affiliations

Affiliations

  • 1 Zhongshan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200032, China.
  • 2 CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Innovation Center for Intervention of Chronic Disease and Promotion of Health, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
  • 3 Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, 200072, China.
  • 4 Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, 200072, China. [email protected].
  • 5 Zhongshan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200032, China. [email protected].
PMID: 36641530 DOI: 10.1038/s42003-023-04425-w
Abstract

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.

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