{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:45:18Z","timestamp":1790675118835,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T00:00:00Z","timestamp":1660521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2022,9]]},"abstract":"\n New Findings<\/jats:title>\n \n \n \n \n What is the central question in this study?<\/jats:bold>\n <\/jats:p>\n Promoting muscle health with regular aerobic exercise can improve mental health through a kynurenine metabolic pathway: do conditions of muscle disease such as muscular dystrophy negatively influence this pathway?<\/jats:p>\n <\/jats:list-item>\n \n \n What is the main finding and its importance?<\/jats:bold>\n <\/jats:p>\n \n The DBA\/2J\n mdx<\/jats:italic>\n model of Duchenne muscular dystrophy exhibits altered kynurenine metabolism with less kynurenic acid and peroxisome proliferator\u2010activated receptor\u2010\u03b3 coactivator 1\u2010\u03b1 and higher levels of tumour necrosis factor \u03b1 mRNA\u00a0\u2013 results associated with anxiety\u2010like behaviour.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Abstract<\/jats:title>\n \n Regular exercise can direct muscle kynurenine (KYN) metabolism toward the neuroprotective branch of the kynurenine pathway thereby limiting the accumulation of neurotoxic metabolites in the brain and contributing to mental resilience. However, the effect of muscle disease on KYN metabolism has not yet been investigated. Previous work has highlighted anxiety\u2010like behaviours in approximately 25% of patients with Duchenne muscular dystrophy (DMD), possibly due to altered KYN metabolism. Here, we characterized KYN metabolism in\n mdx<\/jats:italic>\n mouse models of DMD. Young (8\u201310\u00a0week old) DBA\/2J (D2)\n mdx<\/jats:italic>\n mice, but not age\u2010matched C57BL\/10 (C57)\n mdx<\/jats:italic>\n mice, had lower levels of circulating kynurenic acid (KYNA) and lower KYNA:KYN ratio compared with their respective wild\u2010type (WT) controls. While both C57 and D2\n mdx<\/jats:italic>\n mice displayed signs of anxiety\u2010like behaviour, spending more time in the corners of the arena during a novel object recognition test, this effect was more prominent in D2\n mdx<\/jats:italic>\n mice. Correlational analysis detected a significant negative association between KYNA:KYN levels and time spent in corners in D2 mice, but not C57 mice. In extensor digitorum longus muscles from D2\n mdx<\/jats:italic>\n mice, but not C57\n mdx<\/jats:italic>\n mice, we found lowered protein levels of peroxisome proliferator\u2010activated receptor\u2010\u03b3 coactivator 1\u2010\u03b1 and kynurenine amino transferase\u20101 enzyme when compared with WT. Furthermore, D2\n mdx<\/jats:italic>\n quadriceps muscles had the highest level of tumour necrosis factor \u03b1 expression, which is suggestive of enhanced inflammation. Thus, our pilot work shows that KYN metabolism is altered in D2\n mdx<\/jats:italic>\n mice, with a potential contribution from altered muscle health.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/ep090381","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T06:59:02Z","timestamp":1659337142000},"page":"1029-1036","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Kynurenine metabolism is altered in\n mdx<\/i>\n mice: a potential muscle to brain connection"],"prefix":"10.1113","volume":"107","author":[{"given":"Emily N.","family":"Copeland","sequence":"first","affiliation":[{"name":"Department of Kinesiology Faculty of Applied Health Sciences Brock University St Catharines Ontario Canada"},{"name":"Centre for Bone and Muscle Health Brock University St Catharines Ontario Canada"},{"name":"Centre for Neurosciences Brock University St Catharines Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colton J. F.","family":"Watson","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Faculty of Applied Health Sciences Brock University St Catharines Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kennedy C.","family":"Whitley","sequence":"additional","affiliation":[{"name":"Department of Kinesiology Faculty of Applied Health Sciences Brock University St Catharines Ontario Canada"},{"name":"Centre for Bone and Muscle Health Brock University St Catharines Ontario Canada"},{"name":"Centre for Neurosciences Brock University St Catharines Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley J.","family":"Baranowski","sequence":"additional","affiliation":[{"name":"Centre for Neurosciences Brock University St Catharines Ontario Canada"},{"name":"Department of Health Sciences Faculty of Applied Health Sciences Brock University St Catharines Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel","family":"Kurgan","sequence":"additional","affiliation":[{"name":"Department of Kinesiology Faculty of Applied Health Sciences Brock University St Catharines Ontario Canada"},{"name":"Centre for Bone and Muscle Health Brock University St Catharines Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam J.","family":"MacNeil","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Faculty of Applied Health Sciences Brock University St Catharines Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca E. K.","family":"MacPherson","sequence":"additional","affiliation":[{"name":"Centre for Neurosciences Brock University St Catharines Ontario Canada"},{"name":"Department of Health Sciences Faculty of Applied Health Sciences Brock University St Catharines Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4500-3347","authenticated-orcid":false,"given":"Val A.","family":"Fajardo","sequence":"additional","affiliation":[{"name":"Department of Kinesiology Faculty of Applied Health Sciences Brock University St Catharines Ontario Canada"},{"name":"Centre for Bone and Muscle Health Brock University St Catharines Ontario Canada"},{"name":"Centre for Neurosciences Brock University St Catharines Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Allison","sequence":"additional","affiliation":[{"name":"Department of Kinesiology Faculty of Applied Health Sciences Brock University St Catharines Ontario Canada"},{"name":"St Joseph's Health Care London London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.07.051"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10712-0"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-014-0151-1"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0425-2"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41394-018-0131-2"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00448.2018"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2020.02.018"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-8966(06)80008-8"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.4.1189"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2014.00012"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv460"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2001.tb00750.x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880070903"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-4328(88)90157-X"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2004.11.006"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.1986.tb03900.x"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10040558"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-70987-y"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/2211-5463.13317"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2020.00145"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202002500R"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2018.03.023"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.102700"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/gbb.12301"},{"key":"e_1_2_9_26_1","article-title":"Psychopathological 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