Crhr1, short for corticotropin releasing hormone receptor 1, is a G protein-coupled receptor. It is crucial in the hypothalamic-pituitary-adrenal (HPA) axis, where corticotropin-releasing hormone (CRH) acts as a neuromodulator to initiate basal and stress-related reactions [1]. CRH-Crhr1 signaling also participates in various extrahypothalamic brain circuits, organizing behavioral and humoral responses to stress, and is involved in multiple physiological and pathophysiological processes.

Genetic studies on Crhr1 have provided significant insights. In mice, the Crhr1 antagonist antalarmin alleviated LPS-induced depression-like behavior, suggesting that Crhr1/nectin3 signaling may play a key role in depression-like behaviors [2]. In another study, stress-induced gut dysbiosis in mice was found to be mediated by the CRH-Crhr1-mitochondria pathway. Antagonizing Crhr1 expression or activating mitochondria respiration could improve gut dysbiosis, indicating the importance of Crhr1 in stress-induced gastrointestinal diseases [3].

In conclusion, Crhr1 is essential for the regulation of stress-related physiological and behavioral responses. Studies using mouse models, especially those targeting Crhr1 through antagonist use or genetic modification, have revealed its significance in diseases such as depression and stress-induced gut dysbiosis. These findings provide potential therapeutic targets for stress-related disorders.

References:

1. Dos Santos Claro, Paula A, Silbermins, Micaela, Inda, Carolina, Silberstein, Susana. 2022. CRHR1 endocytosis: Spatiotemporal regulation of receptor signaling. In Progress in molecular biology and translational science, 196, 229-260. doi:10.1016/bs.pmbts.2022.07.015. https://pubmed.ncbi.nlm.nih.gov/36813360/

2. Sun, Jie, Qiu, Lili, Zhang, Hui, Ju, Lingsha, Yang, Jiaojiao. 2023. CRHR1 antagonist alleviates LPS-induced depression-like behaviour in mice. In BMC psychiatry, 23, 17. doi:10.1186/s12888-023-04519-z. https://pubmed.ncbi.nlm.nih.gov/36624454/

3. Zhang, Yiming, Li, Xiaoang, Lu, Siqi, Pei, Fei, Duan, Liping. 2024. Stress triggers gut dysbiosis via CRH-CRHR1-mitochondria pathway. In NPJ biofilms and microbiomes, 10, 93. doi:10.1038/s41522-024-00571-z. https://pubmed.ncbi.nlm.nih.gov/39349483/