{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T01:47:18Z","timestamp":1782265638797,"version":"3.54.5"},"posted":{"date-parts":[[2026,6,22]]},"group-title":"Neuroscience","reference-count":90,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>We constructed a spatially resolved metabolomic atlas of long-term exercise across six major organs in wild-type mice: brain, heart, lung, liver, kidney, and skeletal muscle, cataloguing 224 metabolic features and revealing coordinated inter-organ remodeling. Surprisingly, the brain showed particularly pronounced region-specific adaptation. Because pathological tau associates with synaptic mitochondria from early stages of tauopathy, we extended this multi-organ spatial metabolomic approach to PS19 mice and found that exercise reduced over 70% of observable tau pathology in PS19 hippocampus and restored the mitochondrial-related metabolome. Integrated proteomic and spatial metabolomic analyses identified NADH dehydrogenase Complex I as the convergent node. To test this finding biologically, we expressed the yeast NADH dehydrogenase, Ndi1, in PS19 neurons in the absence of exercise. This increased cerebral antioxidants, restored shuttle-linked metabolites, and reduced tau pathology. Increasing NADH dehydrogenase activity through NDI1 reproduces the core anti-tau and metabolic effects of exercise. These findings provide a molecular mechanism for how exercise may prevent or slow tau pathology accumulation, complementing the human-cohort literature linking exercise to delayed cognitive decline.<\/jats:p>","DOI":"10.64898\/2026.06.16.732673","type":"posted-content","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:55:20Z","timestamp":1782176120000},"source":"Crossref","is-referenced-by-count":0,"title":["A multi-organ spatial metabolomic atlas of exercising mice reveals neuronal Complex I as a convergent and sufficient axis for tau pathology reduction in PS19"],"prefix":"10.64898","author":[{"given":"Terrymar","family":"Medina","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadi","family":"Qui\u00f1ones","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular 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