{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T11:04:48Z","timestamp":1789729488942,"version":"4.0.1"},"reference-count":67,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS134624"],"award-info":[{"award-number":["NS134624"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS135254"],"award-info":[{"award-number":["R01 NS135254"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS122302"],"award-info":[{"award-number":["NS122302"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Spinocerebellar ataxia 1 (SCA1) is a fatal hereditary neurodegenerative disorder with no approved therapies, and gene\u2010targeting strategies have thus far failed in clinical trials. Exercise remains the only intervention shown to provide clinical benefit in patients with spinocerebellar ataxias (SCAs), yet the underlying mechanisms remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using the Atxn1\n                      <jats:sup>154Q\/2Q<\/jats:sup>\n                      knock\u2010in mouse model, we implemented a prolonged voluntary wheel\u2010running paradigm from 4 to 16\u2009weeks of age. Mice were then phenotyped using motor and cognitive behavioral assays. Following euthanasia, cerebellar tissue was harvested for histological analysis and unbiased transcriptomics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Unrestricted exercise rescued motor ataxia but not degeneration in this SCA1 mouse model at the ages in this study. Transcriptional profiling of cerebellar tissue separated wild\u2010type (WT) sedentary and exercise mice by differential gene expression, but in SCA1 mice the most pronounced changes occurred at the level of RNA splicing, particularly in ion channel modules. Exercise led to a significant rescue of splicing events in SCA1 mice, with minimal impact on gene expression changes. Further, both exercised SCA1 and WT mice exhibited splicing patterns more similar to each other than their sedentary counterparts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Together with emerging evidence in other SCAs, our findings confirm aberrant splicing as a central driver of SCA pathophysiology and identify splicing\u2010regulated networks as actionable therapeutic targets. The observed benefits in SCA1 mice suggest that correcting mis\u2010spliced ion channels may be a viable strategy for disease modification across SCAs and related neurodegenerative disorders. ANN NEUROL 2026;100:850\u2013866<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.78282","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T03:49:48Z","timestamp":1781754588000},"page":"850-866","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardiovascular Exercise Drives Neuroprotection in a Mouse Model of Spinocerebellar Ataxia 1 Via Rescue of Aberrant Splicing"],"prefix":"10.1002","volume":"100","author":[{"given":"Isabel","family":"Soto","sequence":"first","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bonomo","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna 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