Integrative Behavioral, Histological and Proteomics Profiling Identifies Cerebellar Drivers of Motor Dysfunction in a Rat Model of Hepatic Encephalopathy

Integrative Behavioral, Histological and Proteomics Profiling Identifies Cerebellar Drivers of Motor Dysfunction in a Rat Model of Hepatic Encephalopathy | 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 Integrative Behavioral, Histological and Proteomics Profiling Identifies Cerebellar Drivers of Motor Dysfunction in a Rat Model of Hepatic Encephalopathy Shambhu Kumar Prasad, Priyanka Thakur, Vishal Vikram Singh, Sanjeeva Srivastava, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6690143/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 Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome resulting from liver dysfunction or portosystemic shunting, characterized by cognitive and motor impairments. Although often considered reversible after liver transplantation, emerging evidence suggests HE may cause lasting neurological damage, underscoring the need to explore its molecular basis. The cerebellum, critical for motor coordination and cognitive functions, is increasingly recognized for its role in HE pathogenesis. This study employed proteomic analyses to investigate molecular alterations in the cerebellum of a thioacetamide-induced moderate-grade HE (MoHE) rat model. Motor deficits were confirmed through rotarod and gait test, showing impaired balance, reduced endurance, and disrupted coordination. Histological analyses revealed degeneration of Purkinje neurons and hypertrophy of Bergmann glial fibers. Label-free quantitative mass spectrometry identified 2,002 proteins, with 65 differentially expressed (35 upregulated, 30 downregulated). Bioinformatic analyses indicated dysregulation of pathways involved in calcium signaling, GTPase cycles, endocytosis, and apoptosis. Protein-protein interaction networks highlighted the interconnected roles of these proteins. Overexpression of RheB, MPPCB, and fetuin-A was validated by western blotting. Immunofluorescence further confirmed the overexpression and cerebellar localization of these proteins, along with lactadherin-a novel protein implicated in HE-in the Granular and Purkinje layers. This study offers a comprehensive molecular profile of cerebellar changes in HE, identifying key proteins and pathways that may contribute to neurological impairments. These findings provide a foundation for developing targeted therapies aimed at mitigating HE-related brain dysfunction and improving clinical outcomes. Hepatic encephalopathy Cerebellum Proteomics Rota rod Gait Analysis Lactadherin Rheb Fetuin-A Full Text Additional Declarations Table 1 is available in the Supplementary Files section. Supplementary Files Supplementarydata.pdf Table1.docx 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-6690143","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":466576475,"identity":"08f77ef1-7fac-41bc-9341-cc14efc38f27","order_by":0,"name":"Shambhu Kumar Prasad","email":"","orcid":"","institution":"Banaras Hindu University","correspondingAuthor":false,"prefix":"","firstName":"Shambhu","middleName":"Kumar","lastName":"Prasad","suffix":""},{"id":466576476,"identity":"543f71e2-6ee6-49fb-92b3-b3868b4182b1","order_by":1,"name":"Priyanka Thakur","email":"","orcid":"","institution":"Banaras Hindu 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