5-HT1A + Treg cells and their associated signaling pathways may be the key mediators determining susceptibility in mouse models of depression

5-HT1A + Treg cells and their associated signaling pathways may be the key mediators determining susceptibility in mouse models of depression | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article 5-HT1A + Treg cells and their associated signaling pathways may be the key mediators determining susceptibility in mouse models of depression Yan-bo Wang, Li-Jun Liu, Xiao-chun Zhang, Bin-bin Bai, Rui Jing, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8541784/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Rationale Chronic social defeat stress (CSDS) can naturally distinguish between susceptible and resistant individuals, and in-depth exploration of its specific mechanisms holds significant potential value for the prevention and treatment of depression. Objective To investigate the key molecular biological mechanisms and signaling pathways that determine susceptibility versus resilience in the CSDS mouse model. Method Adolescent C57BL/6J mice were exposed to CD-1 mouse cages for 10 consecutive days to establish the CSDS model. After distinguishing between susceptible and resilient mice, behavioral indicators were validated in each group. Differentially expressed proteins and pathways were screened using Olink Proteomics technology and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The expression of key cytokine mRNAs, including Il17a, Ifng, and Il4, in the in vitro co-culture system of regulatory T cells (Treg) and microglia was detected using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Result (1) Significant differences in behavioral indicators were observed between the susceptible group and the control group. (2) Olink and KEGG enrichment analyses identified 4 common differentially expressed proteins (EBI3_IL27, LRIG1, NAGK, SPN) and 2 shared pathways (hsa04060 and hsa04657). (3) Co-culture experiments demonstrated that WAY100635 could block 5-HT-induced downregulation of Il17a and Ifng mRNA expression, as well as upregulation of Il4 mRNA. Conclusion In the CSDS model, 5-HT1A + Treg cells and their associated cytokine pathways may be the key mediators determining susceptibility to stress. Depression Chronic social defeat stress Susceptibility Resilience Treg cells Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8541784","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":574105319,"identity":"25784382-856d-4fe5-8320-bf9e6818d5b2","order_by":0,"name":"Yan-bo 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signaling pathways may be the key mediators determining susceptibility in mouse models of depression\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research 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mouse model.\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e \u003cp\u003eAdolescent C57BL/6J mice were exposed to CD-1 mouse cages for 10 consecutive days to establish the CSDS model. After distinguishing between susceptible and resilient mice, behavioral indicators were validated in each group. Differentially expressed proteins and pathways were screened using Olink Proteomics technology and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The expression of key cytokine mRNAs, including Il17a, Ifng, and Il4, in the in vitro co-culture system of regulatory T cells (Treg) and microglia was detected using reverse transcription quantitative polymerase chain reaction (RT-qPCR).\u003c/p\u003e\u003ch2\u003eResult\u003c/h2\u003e \u003cp\u003e(1) Significant differences in behavioral indicators were observed between the susceptible group and the control group. (2) Olink and KEGG enrichment analyses identified 4 common differentially expressed proteins (EBI3_IL27, LRIG1, NAGK, SPN) and 2 shared pathways (hsa04060 and hsa04657). (3) Co-culture experiments demonstrated that WAY100635 could block 5-HT-induced downregulation of Il17a and Ifng mRNA expression, as well as upregulation of Il4 mRNA.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eIn the CSDS model, 5-HT1A\u003csup\u003e+\u003c/sup\u003eTreg cells and their associated cytokine pathways may be the key mediators determining susceptibility to stress.\u003c/p\u003e","manuscriptTitle":"5-HT1A + Treg cells and their associated signaling pathways may be the key mediators determining susceptibility in mouse models of depression","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-14 20:48:33","doi":"10.21203/rs.3.rs-8541784/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e476b083-0193-45b8-97a1-ebd20ded33d4","owner":[],"postedDate":"January 14th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-28T10:56:18+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-14 20:48:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8541784","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8541784","identity":"rs-8541784","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}