{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:45:58Z","timestamp":1786977958808,"version":"build-2736575974"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T00:00:00Z","timestamp":1699401600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP20H00527"],"award-info":[{"award-number":["JP20H00527"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP22K15706"],"award-info":[{"award-number":["JP22K15706"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23H00420"],"award-info":[{"award-number":["JP23H00420"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP22am0401007"],"award-info":[{"award-number":["JP22am0401007"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP22nk0101575"],"award-info":[{"award-number":["JP22nk0101575"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP23bm1423003"],"award-info":[{"award-number":["JP23bm1423003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Spinal and bulbar muscular atrophy (SBMA) is a hereditary neuromuscular disorder caused by the expansion of trinucleotide cytosine\u2013adenine\u2013guanine (CAG) repeats, which encodes a polyglutamine (polyQ) tract in the\n                      <jats:italic>androgen receptor<\/jats:italic>\n                      (\n                      <jats:italic>AR<\/jats:italic>\n                      ) gene. Recent evidence suggests that, in addition to motor neuron degeneration, defective skeletal muscles are also the primary contributors to the pathogenesis in SBMA. While benefits of physical exercise have been suggested in SBMA, underlying mechanism remains elusive.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We investigated the effect of running exercise in a transgenic mouse model of SBMA carrying human\n                      <jats:italic>AR<\/jats:italic>\n                      with 97 expanded CAGs (AR97Q). We assigned AR97Q mice to exercise and sedentary control groups, and mice in the exercise group received 1\u2010h forced running wheel (5\u00a0m\/min) 5\u00a0days a week for 4\u00a0weeks during the early stage of the disease. Motor function (grip strength and rotarod performance) and survival of each group were analysed, and histopathological and biological features in skeletal muscles and motor neurons were evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      AR97Q mice in the exercise group showed improvement in motor function (~40% and ~50% increase in grip strength and rotarod performance, respectively,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05) and survival (median survival 23.6 vs. 16.7\u00a0weeks,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05) with amelioration of neuronal and muscular histopathology (~1.4\u2010fold and ~2.8\u2010fold increase in motor neuron and muscle fibre size, respectively,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001) compared to those in the sedentary group. Nuclear accumulation of polyQ\u2010expanded AR in skeletal muscles and motor neurons was suppressed in the mice with exercise compared to the sedentary mice (~50% and ~30% reduction in 1C2\u2010positive cells in skeletal muscles and motor neurons, respectively,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05). We found that the exercise activated 5\u2032\u2010adenosine monophosphate\u2010activated protein kinase (AMPK) signalling and inhibited mammalian target of rapamycin pathway that regulates protein synthesis in skeletal muscles of SBMA mice. Pharmacological activation of AMPK inhibited protein synthesis and reduced polyQ\u2010expanded AR proteins in C2C12 muscle cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings suggest the therapeutic potential of exercise\u2010induced effect via AMPK activation in SBMA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13344","type":"journal-article","created":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T04:05:41Z","timestamp":1699416341000},"page":"159-172","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Exercise attenuates polyglutamine\u2010mediated neuromuscular degeneration in a mouse model of spinal and bulbar muscular atrophy"],"prefix":"10.1002","volume":"15","author":[{"given":"Tomoki","family":"Hirunagi","sequence":"first","affiliation":[{"name":"Department of Neurology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Nakatsuji","sequence":"additional","affiliation":[{"name":"Department of Neurology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Sahashi","sequence":"additional","affiliation":[{"name":"Department of Neurology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikiyasu","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Neurology Nagoya University Graduate School of Medicine  Nagoya 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