{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T01:00:25Z","timestamp":1777942825197,"version":"3.51.4"},"reference-count":52,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2019,5,8]],"date-time":"2019-05-08T00:00:00Z","timestamp":1557273600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS057198"],"award-info":[{"award-number":["NS057198"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Neurorehabil Neural Repair"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:p>Activity-dependent treatments to enhance peripheral nerve regeneration after injury have shown great promise, and clinical trials implementing them have begun. Success of these treatments requires activity-dependent release of brain-derived neurotrophic factor (BDNF). A single nucleotide polymorphism (SNP) in the bdnf gene known as Val66Met, which is found in nearly one third of the human population, results in defective activity-dependent BDNF secretion and could impact the effectiveness of these therapies. Here, we used a mouse model of this SNP to test the efficacy of treadmill exercise in enhancing axon regeneration in animals both heterozygous (V\/M) and homozygous (M\/M) for the SNP. Axon regeneration was studied 4 weeks after complete transection and repair of the sciatic nerve in both male and female animals, using both electrophysiological and histological outcome measures. Regeneration was enhanced significantly without treatment in V\/M mice, compared with wild type (V\/V) controls. Unlike V\/V mice, treatment of both V\/M and M\/M mice with treadmill exercise did not result in enhanced regeneration. These results were recapitulated in vitro using dissociated neurons containing the light-sensitive cation channel, channelrhodopsin. Three days after plating, neurites of neurons from V\/M and M\/M mice were longer than those of V\/V neurons. In neurons from V\/V mice, but not those from V\/M or M\/M animals, longer neurites were found after optogenetic stimulation. Taken together, Met-carriers possess an intrinsically greater capacity to regenerate axons in peripheral nerves, but this cannot be enhanced further by activity-dependent treatments.<\/jats:p>","DOI":"10.1177\/1545968319846131","type":"journal-article","created":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T01:51:30Z","timestamp":1557366690000},"page":"407-418","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["The Val66Met BDNF Polymorphism and Peripheral Nerve Injury: Enhanced Regeneration in Mouse Met-Carriers Is Not Further Improved With Activity-Dependent Treatment"],"prefix":"10.1177","volume":"33","author":[{"given":"Claire E.","family":"McGregor","sequence":"first","affiliation":[{"name":"Emory University School of Medicine, Atlanta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison M.","family":"Irwin","sequence":"additional","affiliation":[{"name":"Emory 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