{"paper_id":"4dbbd3bf-dedf-40a4-8ab0-37674d1ff39d","body_text":"Modulating Cholinergic Hyperactivity Restores Motor Deficits in Parkinson's Disease, Revealed by Quantitative [18F]VAT PET Imaging Vesicular Acetylcholine Transporter | 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 Modulating Cholinergic Hyperactivity Restores Motor Deficits in Parkinson's Disease, Revealed by Quantitative [18F]VAT PET Imaging Vesicular Acetylcholine Transporter Peizhen Ye, Lei Bi, Yifan Qiu, Min Yang, Yongshan Liu, Yuyi Hou, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7424059/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 To investigate the role of cholinergic neuronal activity in Parkinson's disease (PD), A53T transgenic mice underwent [ 18 F]VAT PET imaging targeting the vesicular acetylcholine transporter. Baseline scans revealed cholinergic hyperactivity in multiple brain regions including amygdala, basal forebrain septum, cortex, hippocampus, hypothalamus, midbrain, striatum and thalamus, while [ 18 F]L-DOPA PET indicated dopaminergic neuron loss in the striatum. After five weeks of montelukast treatment, motor function improved, accompanied by significantly reduced [ 18 F]VAT binding in above brain regions and increased [ 18 F]L-DOPA uptake only in the striatum. [ 18 F]VAT uptake in the hippocampus positively correlated with motor recovery including muscle strength deficits, coordination impairments, and endurance limitations. These results suggest that cholinergic modulation improves motor deficits in PD, and [ 18 F]VAT PET represents a promising tool for monitoring cholinergic responses. Health sciences/Neurology Biological sciences/Neuroscience Parkinson's disease VAChT Cholinergic neuron Neuroimaging Full Text Additional Declarations No competing interests reported. Supplementary Files 2025.0821VATnpjPDSupplementaryfinal.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. 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