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Here, we investigated whether repeated ASO administration reverses brainstem and cerebellar neurochemical abnormalities by magnetic resonance spectroscopy (MRS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Symptomatic SCA3 mice received intracerebroventricular treatment of ASO or vehicle and were compared to wild\u2010type vehicle\u2010treated littermates. To quantify neurochemical changes in treated mice, longitudinal 9.4T MRS of cerebellum and brainstem was performed. Acquired magnetic resonance (MR) group means were analyzed by 2\u2010way analysis of variance mixed\u2010effects sex\u2010adjusted analysis with post hoc Sidak correlation for multiple comparisons. Pearson correlations were used to relate SCA3 pathology and behavior.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MR spectra yielded 15 to 16 neurochemical concentrations in the cerebellum and brainstem. ASO treatment in SCA3 mice resulted in significant total choline rescue and partial reversals of taurine, glutamine, and total\n                      <jats:italic>N<\/jats:italic>\n                      \u2010acetylaspartate across both regions. Some ASO\u2010rescued neurochemicals correlated with reduction in diseased protein and nuclear ATXN3 accumulation. ASO\u2010corrected motor activity correlated with total choline and total\n                      <jats:italic>N<\/jats:italic>\n                      \u2010acetylaspartate levels early in disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      SCA3 mouse cerebellar and brainstem neurochemical trends parallel those in patients with SCA3. Decreased total choline may reflect oligodendrocyte abnormalities, decreased total\n                      <jats:italic>N<\/jats:italic>\n                      \u2010acetylaspartate highlights neuronal health disturbances, and high glutamine may indicate gliosis. ASO treatment fully or partially reversed select neurochemical abnormalities in SCA3 mice, indicating the potential for these measures to serve as noninvasive treatment biomarkers in future SCA3 gene silencing trials. ANN NEUROL 2023;94:658\u2013671\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.26713","type":"journal-article","created":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T01:18:26Z","timestamp":1685150306000},"page":"658-671","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["<scp>Antisense Oligonucleotide<\/scp>\n                    Silencing Reverses Abnormal Neurochemistry in Spinocerebellar Ataxia 3 Mice"],"prefix":"10.1002","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4279-2758","authenticated-orcid":false,"given":"Hayley S.","family":"McLoughlin","sequence":"first","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Gundry","sequence":"additional","affiliation":[{"name":"Center for Magnetic Resonance Research, Department of Radiology, Medical School University of Minnesota  Minneapolis MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orion","family":"Rainwater","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Minnesota  Minneapolis MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen H.","family":"Schuster","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel G.","family":"Wellik","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie J.","family":"Zalon","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael 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