Modulation of OSCP mitigates mitochondrial and synaptic deficits in a mouse model of Alzheimer’s pathology

Modulation of OSCP mitigates mitochondrial and synaptic deficits in a mouse model of Alzheimer’s pathology | 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 Modulation of OSCP mitigates mitochondrial and synaptic deficits in a mouse model of Alzheimer’s pathology Esha Gauba, Shaomei Sui, Jing Tian, Christopher Driskill, Chunxiao Yu, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-25903/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Feb, 2021 Read the published version in Neurobiology of Aging → Version 1 posted You are reading this latest preprint version Abstract Background Oligomycin-sensitivity conferring protein (OSCP) is a critical subunit of mitochondrial F1Fo ATP synthase. OSCP dysfunction has been observed in Alzheimer’s disease (AD) brains and a mouse model with AD-like brain amyloidosis (5xFAD mice). However, whether OSCP dysfunction constitutes a key mitochondrial defect contributing to synaptic injury in AD-related conditions has not been comprehensively investigated. Methods Here, we used a 5xFAD mouse model with OSCP overexpression in neurons (Thy-1 OSCP/5xFAD mice) and cultured neurons from OSCP overexpressing pups in the study. We performed biochemical, immunohistochemical, live cell imaging and electrophysiological as well as behavioral analyses. Results We found that preserved OSCP expression with reduced interaction of amyloid beta (Aβ) with membrane-bound OSCP in Thy-1 OSCP/5xFAD mice. OSCP overexpression also alleviated F1Fo ATP synthase deregulation and preserved mitochondrial function. Moreover, OSCP modulation conferred resistance to Aβ-mediated defects in axonal mitochondrial dynamics & motility. Consistent with protected neuronal mitochondrial function, OSCP overexpression ameliorated hippocampal synaptic injury in 5xFAD mice as demonstrated by preserved synaptic density and synaptic transmission, reduced complement-dependent synapse elimination, leading to improved spatial learning and memory. Conclusion Our findings show the consequences of OSCP dysfunction in the development of synaptic stress in AD-related conditions and they implicate OSCP modulation as a potential therapeutic strategy. Neurobiology of Disease Oligomycin sensitivity-conferring protein mitochondrial F1Fo ATP synthase synaptic injury amyloid beta Alzheimer’s disease Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Full Text Supplementary Files SupplementalFigures.pdf Cite Share Download PDF Status: Published Journal Publication published 01 Feb, 2021 Read the published version in Neurobiology of Aging → 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. 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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-25903","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":536932,"identity":"e90b5be2-5000-426b-8a48-61b97081f420","order_by":1,"name":"Esha Gauba","email":"","orcid":"","institution":"University of Texas at Dallas","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Esha","middleName":"","lastName":"Gauba","suffix":""},{"id":536933,"identity":"690731e3-7aed-466d-adc7-735d7c80b44b","order_by":2,"name":"Shaomei Sui","email":"","orcid":"","institution":"University of Texas at 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Guo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5UlEQVRIie3NsQrCMBCA4SsFuwS7xkF9hZNCcRD7KilCXaoIQhEcLAh5B99CEZyFQJ10dlP3DjoIHU1LF5dUN8H8EJLAfRyATveD1cu7JQ/CdVJ8UElq5e3IFwLDL4gff06s49548t5wfVlu7gz7HljLHVUSMmZmkwejdVKbUoYDPyZJpCYQotngQhKCkpgMaOiqiZ0WZIgJcTKGCw/aaQWhIRoPLpgkrtwijJiSKpKigFPQWSVB1GV48DkJpl0Vse2wc8uiXrsuxPZ8n8092xKbs4rkCfK2t2o8z8g+mdLpdLr/7QVilUETFIwIZgAAAABJRU5ErkJggg==","orcid":"","institution":"University of Texas at Dallas","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Lan","middleName":"","lastName":"Guo","suffix":""},{"id":536942,"identity":"b3548e96-5272-43f2-bc9f-4b415001c045","order_by":11,"name":"Heng Du","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/0lEQVRIiWNgGAWjYBACAyA6+MFAwo6NvYGBgYfBQgYszINfi+FhiQKbZH6eA4wNPAwSPMRoMT7A8yGNceaMBCK1mEskbzggYXCY2eDmG/MHb2okePj7DzA+eNuGW4tlz7GCAwUGh/kMbucYNs45JsEjcSOB2XAuHi0Gx3sMILYAtTTzsAEddoOBTZoXn5bDPAYHeAwOM264eQao5Z8Ej/z5A+y/8WoB2cJjAPI+j2Ezb5sE0IQENma8Ws4cKzgsYQAK5LTCmXP7JHgMbyQ2S845h0fLjeTNHz/8AUXl4Q0f3nyzkZM7f/jghzdluLVgA4wNpKkfBaNgFIyCUYABAGyYVSxd7SCpAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-2661-5818","institution":"University of Texas at Dallas","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Heng","middleName":"","lastName":"Du","suffix":""}],"badges":[],"createdAt":"2020-04-29 05:04:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-25903/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-25903/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1016/j.neurobiolaging.2020.09.018","type":"published","date":"2021-02-01T19:03:45+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":1043606,"identity":"cc8adfc8-e3a0-468c-be33-84364df545a3","added_by":"auto","created_at":"2020-05-07 01:45:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":322980,"visible":true,"origin":"","legend":"Alleviated OSCP aberrations in Thy-1 OSCP/5xFAD mice. (A\u0026B) Immunoblotting analysis of OSCP and other major subunits of F1FO ATP synthase including α, β, γ, a, b, and c in brain mitochondria isolated from 4-5 (A1) and 9-10-month-old (B1) nonTg, 5xFAD, Thy-1 OSCP, and Thy-1 OSCP/5xFAD mice. TOM40 was used as loading control. Two-way ANOVA followed by Bonferroni post hoc analysis. * P \u003c 0.05 5xFAD vs other groups; NS, not significant. n = 3-7 mice per group. (A2\u0026B2) Representative bands of immunoblotting. (C) Duolink PLA positive dots for OSCP/Aβ complex in cortex from 4-5 and 9-10-month-old 5xFAD and Thy-1 OSCP/5xFAD mice. Unpaired student t-test. * P \u003c 0.05. n = 4-5 mice per group. Right panel are the 3-dimensional (3D) representative images of OSCP/Aβ PLA positive dots in cortex. Red dots represent OSCP/Aβ interaction, DAPI labels cell nuclei. Scale bar = 20 µm. (D) Co-immunoprecipitation (Co-IP) of OSCP and Aβ in isolated mitochondria or their membrane fractions from 9-10-month-old nonTg, 5xFAD, Thy-1 OSCP, and Thy-1 OSCP/5xFAD mice. Right panel are the representative images of Co-IP. Unpaired student t-test. \n* P \u003c 0.05. n = 4-5 mice per group.","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-25903/v1/1.png"},{"id":1043609,"identity":"6a506bc7-c808-4643-b58f-369bd3a23ecf","added_by":"auto","created_at":"2020-05-07 01:45:29","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":172852,"visible":true,"origin":"","legend":"Attenuated mitochondrial dysfunction in Thy-1 OSCP/5xFAD mice. (A) F1FO ATP synthase catalytic activity of brain mitochondria isolated from 4-5 (A1) and 9-10-month-old (A2) nonTg, 5xFAD, Thy-1 OSCP, and Thy-1 OSCP/5xFAD mice. Unpaired student t-test. * P \u003c 0.05, *** P \u003c 0.001; NS, not significant. n = 4-7 mice per group. (B) Oligomycin sensitivity of isolated brain mitochondria from 4-5 (B1) and 9-10-month-old (B2) nonTg, 5xFAD, Thy-1 OSCP, and Thy-1 OSCP/5xFAD mice. Unpaired student t-test. * P \u003c 0.05 5xFAD vs Thy1OSCP/5xFAD, *** P \u003c 0.001 5xFAD vs Thy1-OSCP/5xFAD. n = 3-7 mice per group. (C) Mitochondrial respiration control ratio in 4-5 (C1) and 9-10-month-old (C2) old nonTg, 5xFAD, Thy-1 OSCP, and Thy-1 OSCP/5xFAD mice. Unpaired student t-test. * P \u003c 0.05, *** P \u003c 0.001. n = 5-7 mice per group. (D) ATP production in isolated brain mitochondria from 4-5 (D1) and 910-month (D2) nonTg, 5xFAD, Thy-1 OSCP, and Thy-1 OSCP/5xFAD mice. Unpaired student t-test. ** P \u003c 0.01, *** P \u003c 0.001. n = 4-6 mice per group. (E) Mitochondrial ATP:O ratio in 4-5 (E1) and 9-10-month-old (E2) nonTg, 5xFAD, Thy-1 OSCP and Thy-1 OSCP/5xFAD mice. \nUnpaired student t-test. * P \u003c 0.05 vs other groups, *** P \u003c 0.001. n = 4-6 mice per group. (F) \nMitochondrial swelling for 4-5 (F1) and 9-10-month-old (F2) nonTg, 5xFAD, Thy-1 OSCP, and Thy-1 OSCP/5xFAD mice. Unpaired student t-test. * P \u003c 0.05 5xFAD vs Thy1-OSCP/5xFAD, *** P \u003c 0.001 5xFAD vs Thy1-OSCP/5xFAD. n = 5-9 mice per group.","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-25903/v1/2.png"},{"id":1043610,"identity":"5df14dc8-edec-41a3-9759-372f586f2f3c","added_by":"auto","created_at":"2020-05-07 01:45:29","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":334625,"visible":true,"origin":"","legend":"Rescued axonal mitochondrial dynamic and motility by OSCP overexpression in Aβtreated neurons. (A1) The average length of axonal mitochondria was measured in primary nonTg and Thy1-OSCP neurons expressing mitoDsred. The neurons were treated with vehicle, 1 μM Aβ1-42 or 1 μM scramble Aβ for 24 hours. Two-way ANOVA followed by Bonferroni post hoc analysis. *** P \u003c 0.001. n = 227-256 mitochondria per group. (A2) Representative images of axonal mitochondria in primary cultured neurons. Scale bar = 5 µm. (B) Cumulative distribution data of axonal mitochondrial length. n = 227-256 mitochondria per group. (C1) The average volume of axonal mitochondria was analyzed from nonTg and Thy1-OSCP neurons treated with vehicle, 1 μM Aβ1-42 or 1 μM scramble Aβ for 24 hours. Two-way ANOVA followed by Bonferroni post hoc analysis. *** P \u003c 0.001. n = 223-256 mitochondria per group. (C2) Representative 3D images of axonal mitochondria in primary cultured neurons. Scale bar = 5 µm. (D) Cumulative distribution data of axonal mitochondrial volume. n = 223-256 mitochondria per group. (E1) Immunoblotting analysis of mitochondrial dynamic protein in isolated brain mitochondria from 9-10-month-old nonTg, 5xFAD, Thy-1 OSCP, and Thy-1 OSCP/5xFAD mice. p-Dlp1Ser616, T-Dlp1, Mfn2, and OPA1 including short form (OPA1-S) and long form (OPA1-L) were detected. Two-way ANOVA followed by Bonferroni post hoc analysis. * P \u003c 0.05 vs other groups. ** P \u003c 0.01 vs other groups. n = 3-4 mice per group. (E2) Representative bands of immunoblotting in E1. (F-J) Axonal mitochondrial trafficking including percentage of stationary axonal mitochondria (F), percentages of movable (G), anterograding (H), and retrograding (I) mitochondria for vehicle and 24 hours 1 μM Aβ1-42 or 1 μM scramble Aβ-treated nonTg and Thy1-OSCP neurons. Unpaired student t-test. * P \u003c 0.05 vs other groups. (J) Representative kymographs of axonal mitochondrial movement. Scale bar = 10 µm. Data were collected from 3 independent experiments.","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-25903/v1/3.png"},{"id":1043611,"identity":"f210734b-84e1-4f23-b142-504aa45c8e43","added_by":"auto","created_at":"2020-05-07 01:45:29","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":254792,"visible":true,"origin":"","legend":"Preserved synaptic plasticity and transmission in Thy-1 OSCP/5xFAD mice. (A1) \nSynaptic density of 4-5-and 9-10-month-old nonTg, 5xFAD, Thy-1 OSCP, and Thy-1 OSCP/5xFAD mice. Two-way ANOVA followed by Bonferroni post hoc analysis. *** P \u003c 0.001 vs other groups. n = 5 mice per group. (A2) Representative 3D-reconstructed images of synapse staining. vGLUT1 (blue) and PSD95 (red) were used to visualize pre- and post-synaptic components, respectively. The overlaid staining of vGLUT1 and PSD95 indicates synapses. Scale bar = 20 µm. (B) Time course of long-term-potential (LTP) and representative fEPSP responses during the baseline period (black trace) and 30 seconds after theta burst stimulation (red trace) in four groups of mice at 4-5 (B1) and 9-10 (B2) months old. Two-way ANOVA followed by Bonferroni post hoc analysis. * P \u003c 0.05 5xFAD vs other groups. ** P \u003c 0.01 5xFAD vs other groups. n = 6-9 mice per group.","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-25903/v1/4.png"},{"id":1043612,"identity":"ee868df2-cd93-4828-aa04-e25679206293","added_by":"auto","created_at":"2020-05-07 01:45:30","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":314624,"visible":true,"origin":"","legend":"Mitigated synapse trimming by microglia in Thy-1 OSCP/5xFAD mice. (A1) Analysis of C1q-tagged synapses in cortex from 4-5 and 9-10-month-old nonTg, 5xFAD, Thy-1 OSCP, and Thy-1 OSCP/5xFAD mice. Two-way ANOVA followed by Bonferroni post hoc analysis. *** P \u003c 0.001. n = 5 mice per group. (A2) Representative 3D-reconstructed images of C1qtagged synapses in cortex. Synaptophysin (red) represents synapses. The overlaid staining of C1q and synaptophysin indicates C1q-tagged synapses. Scale bar = 10 µm. (B1) Synaptic pruning was examined through co-staining of microglia (Iba1, red) and synapses (synaptophysin, green). Two-way ANOVA followed by Bonferroni post hoc analysis. * P \u003c 0.05, ** P \u003c 0.01. n = 5 mice per group. (B2) 3D representative images of synaptic pruning by microglia. The overlaid staining of Iba1 and synaptophysin indicates microglia-engulfed synapses. Scale bar = 5 µm.","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-25903/v1/5.png"},{"id":1043613,"identity":"576e1ebb-f0d5-4cc2-9d94-e0edb94efe16","added_by":"auto","created_at":"2020-05-07 01:45:30","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":83978,"visible":true,"origin":"","legend":"Improved cognitive function in Thy-1 OSCP/5xFAD mice. Spatial learning \n(A1\u0026A2) and reference memory (B1\u0026B2) of 4-5 and 9-10-month-old nonTg, 5xFAD, Thy-1 OSCP, and Thy-1 OSCP/5xFAD mice. One-way ANOVA followed by Bonferroni post hoc analysis. * P \u003c 0.05 vs other groups, ** P \u003c 0.01 vs other groups. n = 6-9 mice per group.","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-25903/v1/6.png"},{"id":1052005,"identity":"4220d76d-d71b-4e1d-895f-a43a2c7ab8c5","added_by":"auto","created_at":"2020-05-08 11:16:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5873510,"visible":true,"origin":"","legend":"","description":"","filename":"MSforsubmission.pdf","url":"https://assets-eu.researchsquare.com/files/rs-25903/v1/MSforsubmission.pdf"},{"id":1043677,"identity":"e2db620c-4e79-4649-b5bc-320f6185c459","added_by":"auto","created_at":"2020-05-07 01:47:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5980421,"visible":true,"origin":"","legend":"","description":"","filename":"MSforsubmission.pdf","url":"https://assets-eu.researchsquare.com/files/rs-25903/v1_stamped.pdf"},{"id":1043608,"identity":"cbbea720-472a-4885-b748-7f23cdd20f4d","added_by":"auto","created_at":"2020-05-07 01:45:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5873510,"visible":true,"origin":"","legend":"","description":"","filename":"MSforsubmission.pdf","url":"https://assets-eu.researchsquare.com/files/rs-25903/v1/MSforsubmission.pdf"},{"id":13502009,"identity":"b2769a50-26e2-429c-b90c-91acc7b34c60","added_by":"auto","created_at":"2021-09-16 23:12:59","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3097170,"visible":true,"origin":"","legend":"","description":"","filename":"MSforsubmission.pdf","url":"https://assets-eu.researchsquare.com/files/rs-25903/v1_covered.pdf"},{"id":1043607,"identity":"9c6fc9de-d458-41ba-9085-e0f136a455d0","added_by":"auto","created_at":"2020-05-07 01:45:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":1388918,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalFigures.pdf","url":"https://assets-eu.researchsquare.com/files/rs-25903/v1/SupplementalFigures.pdf"}],"financialInterests":"","formattedTitle":"Modulation of OSCP mitigates mitochondrial and synaptic deficits in a mouse model of Alzheimer’s pathology","fulltext":[{"header":"Full Text","content":"\u003cp\u003eThis preprint is available for \u003ca href='/article/rs-25903/latest.pdf' target='_blank'\u003edownload as a PDF\u003c/a\u003e.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"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":"Oligomycin sensitivity-conferring protein, mitochondrial F1Fo ATP synthase, synaptic injury, amyloid beta, Alzheimer’s disease ","lastPublishedDoi":"10.21203/rs.3.rs-25903/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-25903/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e Oligomycin-sensitivity conferring protein (OSCP) is a critical subunit of mitochondrial F1Fo ATP synthase. OSCP dysfunction has been observed in Alzheimer’s disease (AD) brains and a mouse model with AD-like brain amyloidosis (5xFAD mice). However, whether OSCP dysfunction constitutes a key mitochondrial defect contributing to synaptic injury in AD-related conditions has not been comprehensively investigated.\u0026nbsp;\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e Here, we used a 5xFAD mouse model with OSCP overexpression in neurons (Thy-1 OSCP/5xFAD mice) and cultured neurons from OSCP overexpressing pups in the study. We performed biochemical, immunohistochemical, live cell imaging and electrophysiological as well as behavioral analyses.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e We found that preserved OSCP expression with reduced interaction of amyloid beta (Aβ) with membrane-bound OSCP in Thy-1 OSCP/5xFAD mice. OSCP overexpression also alleviated F1Fo ATP synthase deregulation and preserved mitochondrial function. Moreover, OSCP modulation conferred resistance to Aβ-mediated defects in axonal mitochondrial dynamics \u0026amp; motility. Consistent with protected neuronal mitochondrial function, OSCP overexpression ameliorated hippocampal synaptic injury in 5xFAD mice as demonstrated by preserved synaptic density and synaptic transmission, reduced complement-dependent synapse elimination, leading to improved spatial learning and memory.\u0026nbsp;\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e Our findings show the consequences of OSCP dysfunction in the development of synaptic stress in AD-related conditions and they implicate OSCP modulation as a potential therapeutic strategy.\u003c/p\u003e","manuscriptTitle":"Modulation of OSCP mitigates mitochondrial and synaptic deficits in a mouse model of Alzheimer’s pathology","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-05-07 01:43:43","doi":"10.21203/rs.3.rs-25903/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":"26ae4839-2ee0-405b-af83-7d6e9c06ae34","owner":[],"postedDate":"May 7th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":95065,"name":"Neurobiology of Disease"}],"tags":[],"updatedAt":"2021-07-22T19:03:45+00:00","versionOfRecord":{"articleIdentity":"rs-25903","link":"https://doi.org/10.1016/j.neurobiolaging.2020.09.018","journal":{"identity":"neurobiology-of-aging","isVorOnly":true,"title":"Neurobiology of Aging"},"publishedOn":"2021-02-01 19:03:45","publishedOnDateReadable":"February 1st, 2021"},"versionCreatedAt":"2020-05-07 01:43:43","video":"","vorDoi":"10.1016/j.neurobiolaging.2020.09.018","vorDoiUrl":"https://doi.org/10.1016/j.neurobiolaging.2020.09.018","workflowStages":[]},"version":"v1","identity":"rs-25903","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-25903","identity":"rs-25903","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}