Apoptosis Antagonizing Transcription Factor Plays a Dual Role in Remote Preconditioning-Induced Neuroprotection Against Cerebral Ischemia/Reperfusion Injury in Aged Rats

Apoptosis Antagonizing Transcription Factor Plays a Dual Role in Remote Preconditioning-Induced Neuroprotection Against Cerebral Ischemia/Reperfusion Injury in Aged Rats | 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 Apoptosis Antagonizing Transcription Factor Plays a Dual Role in Remote Preconditioning-Induced Neuroprotection Against Cerebral Ischemia/Reperfusion Injury in Aged Rats Wei Jin, Yu-e Zeng, Aydos Alimujiang, Chuancheng Ren, Wei Xu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6716947/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 The elderly population is increasingly susceptible to cerebral ischemia/reperfusion (I/R) injury. Although the potential protective effects of remote preconditioning (RPC) against cerebral ischemia have been explored, there is a paucity of research assessing its influence on elderly individuals. The role of apoptosis antagonizing transcription factor (AATF) in regulating neuronal activity has been reported, but the relationship between AATF and the effects of RPC remain unknown. To investigate the functions of RPC and AATF in cerebral I/R injury in the elderly, we employed aged rats and built models of PRC and cerebral I/R injury and constructed lentiviral Aatf-shRNA vectors. Results showed that RPC reduced brain infarct volume and improved neurological function in aged rats with cerebral I/R injury. Knocking-down AATF suppressed the protective effects of RPC. To investigate the role of AATF in RPC, oxygen glucose deprivation/reoxygenation (OGD/R) model and OGD preconditioning were conducted in vitro. Results showed that OGD preconditioning ameliorated OGD/R-induced cellular DNA fragmentation. AATF contributed to the effects of OGD preconditioning by regulating the cleavage of caspase-3 and modulating the interaction between nuclear apoptosis inducing factors (AIF) and H2AX. Finally, returning to an in vivo setting confirms the role of AATF in RPC. This study highlights the neuroprotective efficacy of RPC in alleviating cerebral I/R injury in aged rodents. Mechanistically, we identify that this protection is mediated by the activation of AATF. Collectively, our results suggest RPC holds promise as a therapeutic strategy to mitigate the detrimental effects of reperfusion therapy in geriatric populations. Notably, AATF exhibits dual regulatory functions in RPC-induced neuroprotection. Ischemia/reperfusion injury Remote preconditioning Apoptosis antagonizing transcription factor Parthanatos Apoptosis Aged rats Full Text Additional Declarations No competing interests reported. Supplementary Files figureS1.tif 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-6716947","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":459920097,"identity":"23d0ea53-4254-4313-8454-9351a53486aa","order_by":0,"name":"Wei Jin","email":"","orcid":"","institution":"Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Jin","suffix":""},{"id":459920098,"identity":"92934484-07e6-4b9c-aa89-dd98e6b3e58c","order_by":1,"name":"Yu-e Zeng","email":"","orcid":"","institution":"Ruijin Hospital Lu Wan Branch, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yu-e","middleName":"","lastName":"Zeng","suffix":""},{"id":459920099,"identity":"105330e1-3d63-4f3f-96e6-a49ab20800fb","order_by":2,"name":"Aydos Alimujiang","email":"","orcid":"","institution":"Shanghai East Hospital Affiliated to Tongji University","correspondingAuthor":false,"prefix":"","firstName":"Aydos","middleName":"","lastName":"Alimujiang","suffix":""},{"id":459920100,"identity":"30f4993a-a520-4f84-80a3-8ef1f7a2dbc0","order_by":3,"name":"Chuancheng Ren","email":"","orcid":"","institution":"The Second Affiliated Hospital of The Chinese University of Hong Kong","correspondingAuthor":false,"prefix":"","firstName":"Chuancheng","middleName":"","lastName":"Ren","suffix":""},{"id":459920101,"identity":"8e7db00d-f346-454a-8e5c-3009b6888694","order_by":4,"name":"Wei Xu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1klEQVRIiWNgGAWjYDACZjApIcfG3nyAIYEELRbG/DzHEojUAgEViTNn5BgQp9bgOO8xad42CcYNB3I+f3i4w46Bv70bv2UGh/nSJGe2STAbHDi7TSLxTDKDxJmzG/BqMTvMYybxsU2CzeBg7zaGxDZmBgOJXCK0JLZJ8Bgc5nn8IbGtnkgtQFskJNt4GIB6DxPWYn+Yx9hyxjkJA34eNpB1x3kI+kWy/4zhbZ6yuvo2+cePP/5sq5bjb+/FrwUIWCSQeTyElIMA8wdiVI2CUTAKRsEIBgBIxkPCN8I2DgAAAABJRU5ErkJggg==","orcid":"","institution":"Shanghai East Hospital Affiliated to Tongji University","correspondingAuthor":true,"prefix":"","firstName":"Wei","middleName":"","lastName":"Xu","suffix":""}],"badges":[],"createdAt":"2025-05-21 13:23:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6716947/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6716947/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":83634823,"identity":"af3670f8-b792-4efc-bf7d-4fb52e5bdb79","added_by":"auto","created_at":"2025-05-29 23:16:30","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1338477,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6716947/v1_covered_46369e88-3836-4320-a240-44470ae0b327.pdf"},{"id":83322298,"identity":"37caa078-0844-4914-8dc2-119e388b122d","added_by":"auto","created_at":"2025-05-23 04:36:20","extension":"tif","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":4814432,"visible":true,"origin":"","legend":"","description":"","filename":"figureS1.tif","url":"https://assets-eu.researchsquare.com/files/rs-6716947/v1/d8cac4bed5f75f25ec391e7b.tif"}],"financialInterests":"No competing interests reported.","formattedTitle":"Apoptosis Antagonizing Transcription Factor Plays a Dual Role in Remote Preconditioning-Induced Neuroprotection Against Cerebral Ischemia/Reperfusion Injury in Aged Rats","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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 Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Ischemia/reperfusion injury, Remote preconditioning, Apoptosis antagonizing transcription factor, Parthanatos, Apoptosis, Aged rats","lastPublishedDoi":"10.21203/rs.3.rs-6716947/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6716947/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"The elderly population is increasingly susceptible to cerebral ischemia/reperfusion (I/R) injury. Although the potential protective effects of remote preconditioning (RPC) against cerebral ischemia have been explored, there is a paucity of research assessing its influence on elderly individuals. The role of apoptosis antagonizing transcription factor (AATF) in regulating neuronal activity has been reported, but the relationship between AATF and the effects of RPC remain unknown. To investigate the functions of RPC and AATF in cerebral I/R injury in the elderly, we employed aged rats and built models of PRC and cerebral I/R injury and constructed lentiviral Aatf-shRNA vectors. Results showed that RPC reduced brain infarct volume and improved neurological function in aged rats with cerebral I/R injury. Knocking-down AATF suppressed the protective effects of RPC. To investigate the role of AATF in RPC, oxygen glucose deprivation/reoxygenation (OGD/R) model and OGD preconditioning were conducted in vitro. Results showed that OGD preconditioning ameliorated OGD/R-induced cellular DNA fragmentation. AATF contributed to the effects of OGD preconditioning by regulating the cleavage of caspase-3 and modulating the interaction between nuclear apoptosis inducing factors (AIF) and H2AX. Finally, returning to an in vivo setting confirms the role of AATF in RPC. This study highlights the neuroprotective efficacy of RPC in alleviating cerebral I/R injury in aged rodents. Mechanistically, we identify that this protection is mediated by the activation of AATF. Collectively, our results suggest RPC holds promise as a therapeutic strategy to mitigate the detrimental effects of reperfusion therapy in geriatric populations. Notably, AATF exhibits dual regulatory functions in RPC-induced neuroprotection.","manuscriptTitle":"Apoptosis Antagonizing Transcription Factor Plays a Dual Role in Remote Preconditioning-Induced Neuroprotection Against Cerebral Ischemia/Reperfusion Injury in Aged Rats","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-23 04:36:15","doi":"10.21203/rs.3.rs-6716947/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":"352a0ee4-7f3a-488f-b5ed-b0200391264d","owner":[],"postedDate":"May 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-05-29T23:08:24+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-23 04:36:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6716947","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6716947","identity":"rs-6716947","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}