Ketogenic Diet Modulates the Proteome of the GAERS Model of Genetic Absence Epilepsy

Ketogenic Diet Modulates the Proteome of the GAERS Model of Genetic Absence Epilepsy | 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 Ketogenic Diet Modulates the Proteome of the GAERS Model of Genetic Absence Epilepsy Aslihan Gunel, Ulku Guler, Aylin Toplu, Nazli Busra Acikgoz, Bora Onat, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8162931/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 This study investigates the effects of a ketogenic diet (KD) on the brain proteome in Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a model of genetic absence epilepsy. The ketogenic diet is a therapeutic intervention for epilepsy, yet its mechanisms remain incompletely understood. Thirty-day-old male GAERS rats were fed a KD (88.8% fat, 10.2% protein, 1% carbohydrate; n = 4) or a normal diet (ND; n = 3), with Wistar rats (n = 3) as healthy controls. A shotgun proteomics approach with data-dependent acquisition was used to analyze the somatosensory cortex (SCx) and hippocampus (Hipp). Data were processed with MaxQuant and Perseus. Compared to Wistars, GAERS-ND rats showed significant alterations in 526 proteins in SCx and 612 in Hipp. KD treatment significantly altered 122 proteins in SCx and 124 in Hipp of GAERS. Notably, KD reversed the expression of 22 proteins in SCx and 32 in Hipp to levels observed in controls. Most KD-affected proteins were synaptic (72% SCx, 76.6% Hipp) and mitochondrial. Pathway analysis indicated KD regulates axon guidance, neurodevelopment, and metabolism in SCx, and autophagy, mitophagy, and Rho GTPase signaling in Hipp. The workflow of the experimental design is provided in Fig. 1. Cellular & Molecular Neuroscience Neurobiology of Disease General Biochemistry Ketogenic diet absence epilepsy proteomics GAERS Full Text Additional Declarations The authors declare no competing interests. Supplementary Files TableS1.SCXGAERSvsWISTARAPR20251.xlsx Differentially expressed proteins in the cortex of GAERS with Normal Diet compared to Wistar normal diet TableS2.HippGAERSvSWISTARAPR2025.xlsx Differentially expressed proteins in the hippocampus of GAERS with Normal Diet compared to Wistar normal diet. TableS3commonproteinsbetweengaersvsWISTARandGAERSKDvsGAERSNDxlsx1.xlsx 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-8162931","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":548051637,"identity":"780a2586-14bf-4dad-ba43-d30030b383dd","order_by":0,"name":"Aslihan 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14:08:20","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":101329,"visible":true,"origin":"","legend":"\u003cp\u003eDifferentially expressed proteins in the cortex of GAERS with Normal Diet compared to Wistar normal diet\u003c/p\u003e","description":"","filename":"TableS1.SCXGAERSvsWISTARAPR20251.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-8162931/v1/19773edb88ac49dab7ee9f8a.xlsx"},{"id":96914899,"identity":"6d9720cb-2c28-4049-b505-e4fc53c258d0","added_by":"auto","created_at":"2025-11-27 14:06:33","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":108643,"visible":true,"origin":"","legend":"\u003cp\u003eDifferentially expressed proteins in the hippocampus of GAERS with Normal Diet compared to Wistar normal diet.\u003c/p\u003e","description":"","filename":"TableS2.HippGAERSvSWISTARAPR2025.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-8162931/v1/d2b5c304be288d273225b932.xlsx"},{"id":96756390,"identity":"a40e6d2b-fb31-48b0-af62-94e5ed4ea2b5","added_by":"auto","created_at":"2025-11-25 18:01:07","extension":"xlsx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":15977,"visible":true,"origin":"","legend":"","description":"","filename":"TableS3commonproteinsbetweengaersvsWISTARandGAERSKDvsGAERSNDxlsx1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-8162931/v1/238f3dbbf368003505d9a172.xlsx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eKetogenic Diet Modulates the Proteome of the GAERS Model of Genetic Absence Epilepsy\u003c/strong\u003e\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Acıbadem University","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"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":"Ketogenic diet, absence epilepsy, proteomics, GAERS","lastPublishedDoi":"10.21203/rs.3.rs-8162931/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8162931/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis study investigates the effects of a ketogenic diet (KD) on the brain proteome in Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a model of genetic absence epilepsy. The ketogenic diet is a therapeutic intervention for epilepsy, yet its mechanisms remain incompletely understood. Thirty-day-old male GAERS rats were fed a KD (88.8% fat, 10.2% protein, 1% carbohydrate; n\u0026thinsp;=\u0026thinsp;4) or a normal diet (ND; n\u0026thinsp;=\u0026thinsp;3), with Wistar rats (n\u0026thinsp;=\u0026thinsp;3) as healthy controls. A shotgun proteomics approach with data-dependent acquisition was used to analyze the somatosensory cortex (SCx) and hippocampus (Hipp). Data were processed with MaxQuant and Perseus. Compared to Wistars, GAERS-ND rats showed significant alterations in 526 proteins in SCx and 612 in Hipp. KD treatment significantly altered 122 proteins in SCx and 124 in Hipp of GAERS. Notably, KD reversed the expression of 22 proteins in SCx and 32 in Hipp to levels observed in controls. Most KD-affected proteins were synaptic (72% SCx, 76.6% Hipp) and mitochondrial. Pathway analysis indicated KD regulates axon guidance, neurodevelopment, and metabolism in SCx, and autophagy, mitophagy, and Rho GTPase signaling in Hipp. The workflow of the experimental design is provided in Fig.\u0026nbsp;1.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","manuscriptTitle":"Ketogenic Diet Modulates the Proteome of the GAERS Model of Genetic Absence Epilepsy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-25 18:01:02","doi":"10.21203/rs.3.rs-8162931/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":"a02c3530-f684-496d-8e4a-fb84cbd14dc3","owner":[],"postedDate":"November 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":58308153,"name":"Cellular \u0026 Molecular Neuroscience"},{"id":58308154,"name":"Neurobiology of Disease"},{"id":58308155,"name":"General Biochemistry"}],"tags":[],"updatedAt":"2025-11-25T18:01:03+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-25 18:01:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8162931","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8162931","identity":"rs-8162931","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}