{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T05:55:54Z","timestamp":1771912554880,"version":"3.50.1"},"reference-count":57,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2020,5,29]],"date-time":"2020-05-29T00:00:00Z","timestamp":1590710400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS045195"],"award-info":[{"award-number":["NS045195"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000016","name":"U.S. Department of Health and Human Services","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Muscle\u2010derived neurotrophic factors may offer therapeutic promise for treating neuromuscular diseases.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We report that a muscle\u2010derived neurotrophic factor, BDNF, rescues synaptic and muscle function in a muscle\u2010type specific manner in mice modelling Kennedy's disease (KD).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We also find that BDNF rescues select molecular mechanisms in slow and fast muscle that may underlie the improved cellular function.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We also report for the first time that expression of BDNF, but not other members of the neurotrophin family, is perturbed in muscle from patients with KD.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Given that muscle BDNF had divergent therapeutic effects that depended on muscle type, a combination of neurotrophic factors may optimally rescue neuromuscular function via effects on both pre\u2010 and postsynaptic function, in the face of disease.<\/jats:p><\/jats:list-item><\/jats:list>\n<\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Deficits in muscle brain\u2010derived neurotrophic factor (BDNF) correlate with neuromuscular deficits in mouse models of Kennedy's disease (KD), suggesting that restoring muscle BDNF might restore function. To test this possibility, transgenic mice expressing human BDNF in skeletal muscle were crossed with \u201897Q\u2019 KD mice. We found that muscle BDNF slowed disease, doubling the time between symptom onset and endstage. BDNF also improved expression of genes in muscle known to play key roles in neuromuscular function, including counteracting the expression of neonatal isoforms induced by disease. Intriguingly, BDNF's ameliorative effects differed between muscle types: synaptic strength was rescued only in slow\u2010twitch muscle, while contractile strength was improved only in fast\u2010twitch muscle. In sum, muscle BDNF slows disease progression, rescuing select cellular and molecular mechanisms that depend on fibre type. Muscle <jats:italic>BDNF<\/jats:italic> expression was also affected in KD patients, reinforcing its translational and therapeutic potential for treating this disorder.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp279208","type":"journal-article","created":{"date-parts":[[2020,4,19]],"date-time":"2020-04-19T17:30:20Z","timestamp":1587317420000},"page":"2719-2739","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Muscle BDNF improves synaptic and contractile muscle strength in Kennedy's disease mice in a muscle\u2010type specific manner"],"prefix":"10.1113","volume":"598","author":[{"given":"Katherine","family":"Halievski","sequence":"first","affiliation":[{"name":"Neuroscience Program Michigan State University  108 Giltner Hall East Lansing MI 48824\u20101115 USA"},{"name":"Program in Neurosciences and Mental Health The Hospital for Sick Children  686 Bay St Toronto ON M5G 0A4 Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youfen","family":"Xu","sequence":"additional","affiliation":[{"name":"Neuroscience Program Michigan State University  108 Giltner Hall East Lansing MI 48824\u20101115 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yazeed W.","family":"Haddad","sequence":"additional","affiliation":[{"name":"Neuroscience Program Michigan State University  108 Giltner Hall East Lansing MI 48824\u20101115 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu Ping","family":"Tang","sequence":"additional","affiliation":[{"name":"Neuroscience Program Michigan State University  108 Giltner Hall East Lansing MI 48824\u20101115 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichiro","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Neurology Nagoya University Graduate School of Medicine  65 Tsurumai\u2010cho, Showa\u2010ku Nagoya 466\u20138550 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahisa","family":"Katsuno","sequence":"additional","affiliation":[{"name":"Department of Neurology Nagoya University Graduate School of Medicine  65 Tsurumai\u2010cho, Showa\u2010ku Nagoya 466\u20138550 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9302-4663","authenticated-orcid":false,"given":"Hiroaki","family":"Adachi","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Occupational and Environment Health School of Medicine  1\u20101 Iseigaoka, Yahatanishi\u2010ku Kitakyushu Fukuoka 807\u20138555 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gen","family":"Sobue","sequence":"additional","affiliation":[{"name":"Department of Neurology Nagoya University Graduate School of Medicine  65 Tsurumai\u2010cho, Showa\u2010ku Nagoya 466\u20138550 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. Marc","family":"Breedlove","sequence":"additional","affiliation":[{"name":"Neuroscience Program Michigan State University  108 Giltner Hall East Lansing MI 48824\u20101115 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia L.","family":"Jordan","sequence":"additional","affiliation":[{"name":"Neuroscience Program Michigan State University  108 Giltner Hall East Lansing MI 48824\u20101115 USA"},{"name":"Physiology Department Michigan State University  108 Giltner Hall East Lansing MI 48824\u20101115 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,5,29]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.46.5.1244"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.12.027"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0808-04.2004"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e10-02-0154"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.03.001"},{"key":"e_1_2_5_7_1","first-page":"2441","article-title":"Conditional BDNF delivery from astrocytes rescues memory deficits, spine density, and synaptic properties in the 5xFAD mouse model of Alzheimer disease","volume":"39","author":"Pins B","year":"2019","journal-title":"J Neurosci"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-45106-5_5"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.11.015"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00469.2010"},{"key":"e_1_2_5_11_1","doi-asserted-by":"crossref","first-page":"4911","DOI":"10.1016\/S0021-9258(18)61283-9","article-title":"Muscle acetylcholine receptor biosynthesis. Regulation by transcript availability","volume":"262","author":"Evans S","year":"1987","journal-title":"J Biol Chem"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2014.01.019"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2676-10.2010"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2010.00250.x"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2015.04.013"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.45.11.1012"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1247\/csf.22.147"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1159\/000313682"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2008.12.009"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0151376"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00834-6"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2012.05.007"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2014.07.001"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr380"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.18.7.671"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-45106-5_6"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2013.108"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-005-0397-y"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-64076-5.00040-5"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.02.008"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/363350a0"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.10558"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-009-1364-1"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3599-11.2011"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1996.0253"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8066451"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07583.x"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2791"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705501104"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00583.2003"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00886.2014"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.23813"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/0960-8966(91)90103-Y"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.07.019"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c120033"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2015.4321"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.9.e36"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.20714"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1550-4"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000335970.78664.36"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-10-03256.1996"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.52.7.1427"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.111310"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(97)00497-1"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3485-15.2016"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0168846"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020739831778"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28773."}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP279208","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/JP279208","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP279208","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T04:19:45Z","timestamp":1693887585000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP279208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,29]]},"references-count":57,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1113\/JP279208"],"URL":"https:\/\/doi.org\/10.1113\/jp279208","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,29]]},"assertion":[{"value":"2019-11-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}