Callosal Glia, GABAergic Interneurons, and Apoptotic Profiles in the Brains of Cypermethrin-Exposed Male and Female Rats

Callosal Glia, GABAergic Interneurons, and Apoptotic Profiles in the Brains of Cypermethrin-Exposed Male and Female 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 Short Report Callosal Glia, GABAergic Interneurons, and Apoptotic Profiles in the Brains of Cypermethrin-Exposed Male and Female Rats Oloyede Priscilla, Abdulrauf Aisha, Eduviere Faith Akpevweoghene, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9114606/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 13 You are reading this latest preprint version Abstract Background Cypermethrin, a Type II pyrethroid insecticide, has been linked to neurotoxicity. However, its effects on the corpus callosum, the brain's largest white matter tract essential for interhemispheric communication, remain poorly understood, particularly regarding sex-dependent vulnerability. This study examined sex-dependent effects of cypermethrin on the corpus callosum of Wistar rats, focusing on white matter integrity, glial populations, GABAergic interneurons, and apoptotic profiles. Methods Sixty adult Wistar rats (30 male, 30 female) were randomly allocated into six groups: male and female controls (corn oil), low-dose cypermethrin (6.25 mg/kg), and high-dose cypermethrin (12.5 mg/kg). Treatments were administered orally for 28 consecutive days. Behavioral assessment utilized the hole-board test. Biochemical analysis measured brain-derived neurotrophic factor (BDNF) and total protein. Immunohistochemical markers (GFAP, IBA-1, parvalbumin, cleaved caspase-3) and H&E staining were evaluated in the corpus callosum. Results Cypermethrin induced sex-dependent behavioral changes: males showed increased rearing frequency while females showed decreased rearing. BDNF concentrations significantly decreased in low-dose males (p = 0.0079) and females (p = 0.0039), with partial recovery in high-dose females. GFAP-positive astrocyte density decreased in exposed males but increased in low-dose females (p = 0.024). IBA-1-positive microglia decreased significantly in both sexes, particularly in low-dose groups (males: p = 0.0001; females: p = 0.0075). Parvalbumin-positive GABAergic interneuron density decreased in low-dose males (p = 0.029) and both female groups. Cleaved caspase-3 expression increased in all treated groups, with high-dose males most affected (p < 0.0001). H&E staining revealed dose-dependent cellular density reductions, greatest in high-dose males (p = 0.0001). Conclusion Cypermethrin induced sex-dependent white matter neurotoxicity, with males showing greater susceptibility than females. Cypermethrin corpus callosum white matter glial cells GABAergic interneurons neurotoxicity apoptosis immunohistochemistry Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 17 Apr, 2026 Reviews received at journal 16 Apr, 2026 Reviewers agreed at journal 06 Apr, 2026 Reviews received at journal 01 Apr, 2026 Reviews received at journal 26 Mar, 2026 Reviewers agreed at journal 23 Mar, 2026 Reviewers agreed at journal 21 Mar, 2026 Reviewers agreed at journal 20 Mar, 2026 Reviewers invited by journal 19 Mar, 2026 Editor assigned by journal 19 Mar, 2026 Editor invited by journal 19 Mar, 2026 Submission checks completed at journal 19 Mar, 2026 First submitted to journal 19 Mar, 2026 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. 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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-9114606","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":610632752,"identity":"0361d02e-7199-486d-8c3f-d58b9ee44f93","order_by":0,"name":"Oloyede Priscilla","email":"","orcid":"","institution":"University of Ilorin","correspondingAuthor":false,"prefix":"","firstName":"Oloyede","middleName":"","lastName":"Priscilla","suffix":""},{"id":610632753,"identity":"93ddcb48-037e-4524-8619-2ebb5463e422","order_by":1,"name":"Abdulrauf Aisha","email":"","orcid":"","institution":"University of Ilorin","correspondingAuthor":false,"prefix":"","firstName":"Abdulrauf","middleName":"","lastName":"Aisha","suffix":""},{"id":610632754,"identity":"6e005b40-c9e9-4bb0-8fde-f2ec177071c5","order_by":2,"name":"Eduviere Faith Akpevweoghene","email":"","orcid":"","institution":"University of Ilorin","correspondingAuthor":false,"prefix":"","firstName":"Eduviere","middleName":"Faith","lastName":"Akpevweoghene","suffix":""},{"id":610632755,"identity":"4051e32d-eb41-4fd2-aa4c-28039652b067","order_by":3,"name":"Oladimeji Mufutau Oladele","email":"","orcid":"","institution":"University of Ilorin","correspondingAuthor":false,"prefix":"","firstName":"Oladimeji","middleName":"Mufutau","lastName":"Oladele","suffix":""},{"id":610632756,"identity":"3924f628-0da8-44d6-b9f7-da510aee5663","order_by":4,"name":"Olanrewaju Ridwan","email":"","orcid":"","institution":"University of Ilorin","correspondingAuthor":false,"prefix":"","firstName":"Olanrewaju","middleName":"","lastName":"Ridwan","suffix":""},{"id":610632757,"identity":"dee3ec70-34be-4f55-8aca-a9016a721eb1","order_by":5,"name":"Omole Precious","email":"","orcid":"","institution":"University of Ilorin","correspondingAuthor":false,"prefix":"","firstName":"Omole","middleName":"","lastName":"Precious","suffix":""},{"id":610632758,"identity":"e8cab47d-633b-4472-8b4c-35896583994c","order_by":6,"name":"Afodun Adam","email":"","orcid":"","institution":"Busitema University","correspondingAuthor":false,"prefix":"","firstName":"Afodun","middleName":"","lastName":"Adam","suffix":""},{"id":610632759,"identity":"18f7c7ca-cb64-4f8c-a957-cf470636b375","order_by":7,"name":"Danwahab Olanrewaju Ambali","email":"","orcid":"","institution":"Kwara State University","correspondingAuthor":false,"prefix":"","firstName":"Danwahab","middleName":"Olanrewaju","lastName":"Ambali","suffix":""},{"id":610632760,"identity":"96c95166-acb0-4dec-80a2-86680c34e3fb","order_by":8,"name":"Oyeniyi Joseph Oludare","email":"","orcid":"","institution":"University of Ilorin","correspondingAuthor":false,"prefix":"","firstName":"Oyeniyi","middleName":"Joseph","lastName":"Oludare","suffix":""},{"id":610632761,"identity":"90f52c4a-d0aa-43ba-9ae0-d06b55601ecd","order_by":9,"name":"Jaji-Sulaimon Rukayat","email":"","orcid":"","institution":"University of Ilorin","correspondingAuthor":false,"prefix":"","firstName":"Jaji-Sulaimon","middleName":"","lastName":"Rukayat","suffix":""},{"id":610632762,"identity":"16b5aa62-af9c-49ac-b148-32872fb56ff0","order_by":10,"name":"Moyosore S. 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However, its effects on the corpus callosum, the brain's largest white matter tract essential for interhemispheric communication, remain poorly understood, particularly regarding sex-dependent vulnerability. This study examined sex-dependent effects of cypermethrin on the corpus callosum of Wistar rats, focusing on white matter integrity, glial populations, GABAergic interneurons, and apoptotic profiles.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eSixty adult Wistar rats (30 male, 30 female) were randomly allocated into six groups: male and female controls (corn oil), low-dose cypermethrin (6.25 mg/kg), and high-dose cypermethrin (12.5 mg/kg). Treatments were administered orally for 28 consecutive days. Behavioral assessment utilized the hole-board test. Biochemical analysis measured brain-derived neurotrophic factor (BDNF) and total protein. Immunohistochemical markers (GFAP, IBA-1, parvalbumin, cleaved caspase-3) and H\u0026amp;E staining were evaluated in the corpus callosum.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eCypermethrin induced sex-dependent behavioral changes: males showed increased rearing frequency while females showed decreased rearing. BDNF concentrations significantly decreased in low-dose males (p\u0026thinsp;=\u0026thinsp;0.0079) and females (p\u0026thinsp;=\u0026thinsp;0.0039), with partial recovery in high-dose females. GFAP-positive astrocyte density decreased in exposed males but increased in low-dose females (p\u0026thinsp;=\u0026thinsp;0.024). IBA-1-positive microglia decreased significantly in both sexes, particularly in low-dose groups (males: p\u0026thinsp;=\u0026thinsp;0.0001; females: p\u0026thinsp;=\u0026thinsp;0.0075). Parvalbumin-positive GABAergic interneuron density decreased in low-dose males (p\u0026thinsp;=\u0026thinsp;0.029) and both female groups. Cleaved caspase-3 expression increased in all treated groups, with high-dose males most affected (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). H\u0026amp;E staining revealed dose-dependent cellular density reductions, greatest in high-dose males (p\u0026thinsp;=\u0026thinsp;0.0001).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eCypermethrin induced sex-dependent white matter neurotoxicity, with males showing greater susceptibility than females.\u003c/p\u003e","manuscriptTitle":"Callosal Glia, GABAergic Interneurons, and Apoptotic Profiles in the Brains of Cypermethrin-Exposed Male and Female Rats","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-24 14:30:25","doi":"10.21203/rs.3.rs-9114606/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-17T12:43:57+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-16T16:07:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"186759819888076189247944547283659101525","date":"2026-04-06T15:49:49+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-01T14:50:42+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-26T14:57:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"145186297104464659153486471178131527074","date":"2026-03-23T11:07:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"279016718310507196999069604216944456906","date":"2026-03-21T15:47:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"196109721315441847216384049148357129646","date":"2026-03-20T12:38:08+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-20T02:12:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-20T02:10:09+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-19T16:29:45+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-19T14:12:54+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Research Notes","date":"2026-03-19T13:12:17+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-research-notes","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"resn","sideBox":"Learn more about [BMC Research Notes](http://bmcresnotes.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/resn/default.aspx","title":"BMC Research Notes","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7db1adf3-8aa6-4ec6-8c7f-d266f14081ec","owner":[],"postedDate":"March 24th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-15T12:39:17+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-24 14:30:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9114606","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9114606","identity":"rs-9114606","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}