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SCA5 arises from mutations in the \u03b2-III spectrin gene (<jats:italic>SPTBN2<\/jats:italic>) with mice lacking \u03b2-III spectrin function (\u03b2-III<jats:sup>\u2212\/\u2212<\/jats:sup>) mirroring the human clinical phenotype. This study finds evidence for dysregulated calcium homeostasis in \u03b2-III<jats:sup>\u2212\/\u2212<\/jats:sup> mice as evidenced by enhanced auto-phosphorylation of calcium-calmodulin dependent kinase II (CaMKII), a major calcium sensor in cells, and phosphorylation of several CaMKII targets. Mibefradil, an inhibitor of calcium channels, was also found to improve disordered \u03b2-III<jats:sup>\u2212\/\u2212<\/jats:sup> Purkinje cell dendritic morphology in vitro. However, key to evaluation of potential treatments in vivo\u00a0is the ability to assess relevant changes at later stages of disease in \u03b2-III<jats:sup>\u2212\/\u2212<\/jats:sup> mice, which has previously been problematic. Here the CatWalk XT system was successful in detecting differences in both truncal stability and interlimb coordination across the disease course of \u03b2-III<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Building on these findings CatWalk analysis showed trimethadione, a selective T-type calcium channel inhibitor, but not riluzole nor verapamil, significantly improved interlimb coordination of 8-month-old \u03b2-III<jats:sup>\u2212\/\u2212<\/jats:sup> mice. These findings highlight the CatWalk XT system as a valuable tool to assess age-dependence of motor function and that modulation of T-type calcium channels has therapeutic potential for SCAs.<\/jats:p>","DOI":"10.1038\/s41598-025-05511-1","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T15:23:51Z","timestamp":1751383431000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Automated gait analysis indicates efficacy of T-type calcium channel inhibition for mitigation of disrupted calcium signalling in an SCA5 mouse model"],"prefix":"10.1038","volume":"15","author":[{"given":"Daumante","family":"Suminaite","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nurul Fatihah","family":"Talib","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie Jane","family":"Pettegree","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han Chew Gaelan","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yvonne Louise","family":"Odey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma Margaret","family":"Perkins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alastair Robert","family":"Lyndon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul Andrew","family":"Skehel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mandy","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"5511_CR1","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1007\/s00415-018-9076-4","volume":"266","author":"R Sullivan","year":"2019","unstructured":"Sullivan, R., Yau, W. 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