Circadian disruption coincides with morphological changes in the suprachiasmatic nucleus in a genetic α-synuclein rat model of early Parkinson's disease

Circadian disruption coincides with morphological changes in the suprachiasmatic nucleus in a genetic α-synuclein rat model of early Parkinson's disease | 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 Article Circadian disruption coincides with morphological changes in the suprachiasmatic nucleus in a genetic α-synuclein rat model of early Parkinson's disease Hanna Weber, Meike Statz, Nicolas Casadei, Olaf Riess, Wiebke Hermann, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7816986/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Disruption of circadian rhythms are a key feature of neurodegenerative diseases and a non-motor feature of Parkinson’s disease, which significantly contribute to an impaired health-related quality of life; yet, the underlying mechanisms are only partially understood. Preclinical animal models with neuropathological and symptomatic significance might contribute to a better understanding of circadian dysfunction. Here we investigated circadian modulation of motor and non-motor behavior as well as structural integrity of the suprachiasmatic nucleus in a genetic rat model of Parkinson’s disease with overexpression of human α-synuclein and wild-type controls. Behavioral testing in three month-old animals revealed robust circadian phase–dependent modulation of exploratory activity, locomotion, sucrose preference, and olfaction-guided feeding in wild-type rats, which was absent in their human α-synuclein littermates. Histological analyses demonstrated reduced overall cell density and pronounced α-synuclein accumulation in the suprachiasmatic nucleus of transgenic rats, accompanied by altered cellular composition, including increased proportions of NeuN+ neurons, Orexin A+ fibres, and Iba1+ microglia. Notably, α-synuclein load was positively correlated with Orexin A+ fibres and Iba1+ cell counts, suggesting a link between protein aggregation, neuroinflammation, and altered circadian regulation. Together, these findings indicate that α-synuclein rats exhibit disrupted circadian flexibility at both behavioral and cellular levels already at an early disease stage with very mild motor impairment, providing a translational model to study different aspects of circadian dysfunction in Parkinson’s disease. Biological sciences/Neuroscience Biological sciences/Physiology Full Text Additional Declarations No competing interests reported. Supplementary Files CircadiandisruptionsinSNCAratsSUPPLEMENTS.zip Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 09 Dec, 2025 Reviews received at journal 04 Dec, 2025 Reviewers agreed at journal 26 Nov, 2025 Reviewers agreed at journal 25 Nov, 2025 Reviews received at journal 05 Nov, 2025 Reviewers agreed at journal 13 Oct, 2025 Reviewers agreed at journal 13 Oct, 2025 Reviewers invited by journal 12 Oct, 2025 Editor assigned by journal 11 Oct, 2025 Submission checks completed at journal 11 Oct, 2025 First submitted to journal 09 Oct, 2025 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-7816986","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":533647309,"identity":"1b52f5da-d878-4689-bd66-5fd932f1c81c","order_by":0,"name":"Hanna 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