{"title":"Rheb in central amygdala somatostatin neurons regulates chronic itch and anxiety-like behaviors.","authors":"Zhenhua Qi, Chao Tian, Xiaorui Jin, Qian Pan, Sipin Zhang, Ji Hu, Jingdun Xie","doi":"10.1016/j.celrep.2026.118231","DOIUrl":null,"url":null,"abstract":"<p><p>Chronic itch represents a significant clinical challenge that substantially impairs patients' quality of life, yet its underlying neural circuit and molecular mechanisms remain elusive. Here, we demonstrate that somatostatin-expressing (SST) neurons in the central amygdala (CeA) are activated and functionally required in a mouse model of diphenylcyclopropenone (DCP)-induced chronic itch. Transcriptomic profiling further revealed upregulation of Ras homolog enriched in brain (Rheb) within DCP-TRAPed CeA SST neurons. Notably, Rheb knockdown suppressed the hyperexcitability of CeA SST neurons and alleviated chronic itch-related scratching and anxiety-like behaviors in DCP-treated mice. Conversely, Rheb overexpression promoted scratching and anxiety-like behaviors in naive mice. Collectively, these findings delineate a Rheb-regulated CeA SST neuronal mechanism that contributes to chronic itch-related scratching and anxiety-like behaviors, highlighting a potential molecular target for therapeutic intervention in chronic itch.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"45 11","pages":"118231"},"PeriodicalIF":7.7000,"publicationDate":"2026-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell reports","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.celrep.2026.118231","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Chronic itch represents a significant clinical challenge that substantially impairs patients' quality of life, yet its underlying neural circuit and molecular mechanisms remain elusive. Here, we demonstrate that somatostatin-expressing (SST) neurons in the central amygdala (CeA) are activated and functionally required in a mouse model of diphenylcyclopropenone (DCP)-induced chronic itch. Transcriptomic profiling further revealed upregulation of Ras homolog enriched in brain (Rheb) within DCP-TRAPed CeA SST neurons. Notably, Rheb knockdown suppressed the hyperexcitability of CeA SST neurons and alleviated chronic itch-related scratching and anxiety-like behaviors in DCP-treated mice. Conversely, Rheb overexpression promoted scratching and anxiety-like behaviors in naive mice. Collectively, these findings delineate a Rheb-regulated CeA SST neuronal mechanism that contributes to chronic itch-related scratching and anxiety-like behaviors, highlighting a potential molecular target for therapeutic intervention in chronic itch.
期刊介绍：
Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted.
The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership.
The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.
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