Impaired Macroautophagy in Oligodendrocyte Precursor Cells Suppresses Neuronal Plasticity via a Senescence Associated Signaling

Impaired Macroautophagy in Oligodendrocyte Precursor Cells Suppresses Neuronal Plasticity via a Senescence Associated Signaling | 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 Impaired Macroautophagy in Oligodendrocyte Precursor Cells Suppresses Neuronal Plasticity via a Senescence Associated Signaling Quan-Hong Ma, Hong Chen, Yan-Yun Sun, Qi-Fa Li, Yu-Tong Du, Na-Na Hu, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3926942/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract Aging drives cognitive decline in the adult brain with unclear mechanisms. Previously, oligodendrocyte precursor cells (OPCs), the source cells of myelin-forming cells in the central nervous system, have been linked to brain aging by their compromised differentiation and regeneration capability. Whether a myelination-independent function of OPCs is involved in brain aging remains unknown. In this study, we herein report a myelination-independent role of OPCs in exaggerating cognitive decline in the aging brain via suppressing neuronal plasticity. Our results demonstrate that macroautophagic flux declines in aged OPCs. Inactivation of autophagy promotes the senescence of OPCs, which activates CCL3/5-CCR5 signaling. Through this, autophagy-defective OPCs impair glutamatergic transmission, neuronal excitability, and long-term potentiation (LTP), exaggerating the cognitive decline in the aging brain. Our study, for the first time, demonstrates a myelination-independent role of OPCs in brain aging and identifies that a declined autophagy in OPCs is a pivotal factor in driving aging-associated cognitive decline. Biological sciences/Neuroscience/Cognitive ageing Biological sciences/Neuroscience/Learning and memory Biological sciences/Neuroscience/Cellular neuroscience Biological sciences/Neuroscience/Neural ageing autophagy OPCs aging senescence memory neuronal plasticity Full Text Additional Declarations The authors declare no competing interests. Supplementary Files SupplementaryFiguresandFigurelegends.pdf Supplementarymaterialsandmethods.pdf Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions 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. 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