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- W4316096809 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." @default.
- W4316096809 created "2023-01-14" @default.
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- W4316096809 date "2023-01-14" @default.
- W4316096809 modified "2023-09-26" @default.
- W4316096809 title "Inhibition of c-Jun in AgRP neurons increases stress-induced anxiety and colitis susceptibility" @default.
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- W4316096809 doi "https://doi.org/10.1038/s42003-023-04425-w" @default.
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