{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:12:40Z","timestamp":1790770360798,"version":"4.1.0"},"reference-count":67,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2015,11,15]],"date-time":"2015-11-15T00:00:00Z","timestamp":1447545600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic nerve injuries are notorious for their poor regenerative outcomes. Here, we addressed the question of whether the established reduced ability of injured motoneurons to regenerate their axons with time of disconnection with targets (chronic axotomy) is associated with a failure of injured motoneurons to express and sustain their expression of regeneration\u2010associated genes. Sciatic motoneurons were prevented from regenerating by ligation of the transected nerves (chronic axotomy), and then subjected to a second nerve transection (acute axotomy) to mimic the clinical surgical procedure of refreshing the proximal nerve stump prior to delayed nerve repair. The expression of \u03b1<jats:sub>1<\/jats:sub>\u2010tubulin, actin and GAP\u201043 mRNA was analysed in axotomized sciatic motoneurons by the use of <jats:italic>in\u00a0situ<\/jats:italic> hybridization followed by autoradiography and silver grain quantification. The expression of these regeneration\u2010associated genes by naive (acutely) axotomized motoneurons declined exponentially, to reach baseline levels within 6\u00a0months. These chronically injured motoneurons responded to a refreshment axotomy by elevating the expression of the genes to the same levels as in acutely (i.e. for the first time) axotomized sciatic motoneurons. However, the expression of these declined more rapidly than after acute axotomy. We conclude that a progressive decline in the expression of the regeneration\u2010associated genes in chronically axotomized motoneurons and the even more rapid decline in their expression in response to a refreshment axotomy may explain why the regenerative capacity of chronically axotomized neurons declines with time.<\/jats:p>","DOI":"10.1111\/ejn.13070","type":"journal-article","created":{"date-parts":[[2015,9,15]],"date-time":"2015-09-15T08:18:57Z","timestamp":1442305137000},"page":"2783-2791","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Regeneration\u2010associated genes decline in chronically injured rat sciatic motoneurons"],"prefix":"10.1111","volume":"42","author":[{"given":"Tessa","family":"Gordon","sequence":"first","affiliation":[{"name":"Neuroscience and Mental Health Institute Faculty of Medicine and Dentistry University of Alberta Edmonton AB T6G 2S2 Canada"},{"name":"Department of Surgery Division of Plastic Reconstructive Surgery 5549A The Hospital for Sick Children  555 University Avenue Toronto ON M5G 1X8 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfram","family":"Tetzlaff","sequence":"additional","affiliation":[{"name":"ICORD (International Collaboration on Repair Discoveries) Blusson Spinal Cord Centre  818\u00a0W. 10th Avenue Vancouver BC V5Z 1M9 Canada"},{"name":"Departments of Zoology and Surgery University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,11,15]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2008.06.005"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:CEMN.0000022770.66463.f7"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80360-2"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)64018-2"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.06.021"},{"key":"e_1_2_6_7_1","volume-title":"Current Protocols in Molecular Biology","author":"Ausubel F.M.","year":"1987"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90616-7"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.494"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(88)90509-4"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02780547"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.64020850.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/82881"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-18-07161.2001"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2245-02.2004"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2002.02077.x"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(00)00254-2"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.10.004"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)90402-2"},{"key":"e_1_2_6_20_1","doi-asserted-by":"crossref","first-page":"9936","DOI":"10.1523\/JNEUROSCI.18-23-09936.1998","article-title":"Acetylcholinesterase gene expression in axotomized rat facial motoneurons is differentially regulated by neurotrophins: correlation with trkB and trkC mRNA levels and isoforms","volume":"18","author":"Fernandes K.J.","year":"1998","journal-title":"J. Neurosci."},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19991129)414:4<495::AID-CNE6>3.0.CO;2-S"},{"key":"e_1_2_6_22_1","first-page":"309","article-title":"Cholinesterase activity in the hypoglossal nucleus of the rat and the changes produced by axotomy: a light and electron microscopic study","volume":"119","author":"Flumerfelt B.A.","year":"1975","journal-title":"J. Anat."},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-07-02534.2000"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-05-03876.1995"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-05-03886.1995"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02740621"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.123.2.455"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7770776"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1227\/01.NEU.0000255412.63184.CC"},{"key":"e_1_2_6_30_1","first-page":"289","volume-title":"Somatic and Autonomic Nerve\u2010Muscle Interactions","author":"Gordon T.","year":"1983"},{"key":"e_1_2_6_31_1","first-page":"903","volume-title":"Nerves and Nerve Injuries","author":"Gordon T.","year":"2015"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1123\/mcj.13.4.412"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6156-10.2011"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2014.10.022"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(75)90170-3"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00770-0"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(96)01000-4"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.09-03-00893.1989"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.12.4530"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(80)90144-4"},{"key":"e_1_2_6_41_1","first-page":"46","article-title":"A gene network perspective on axonal regeneration","volume":"4","author":"Kesteren R.E.","year":"2011","journal-title":"Front. Mol. Neurosci."},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1996.tb01588.x"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-24-09583.1997"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.052308899"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.149.7.1455"},{"issue":"2","key":"e_1_2_6_46_1","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1113\/jphysiol.1995.sp020982","article-title":"Effects of age on aneural regeneration of soleus muscle in rat","volume":"488","author":"Lewis D.M.","year":"1995","journal-title":"J. Physiol."},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-6-19"},{"key":"e_1_2_6_48_1","doi-asserted-by":"crossref","first-page":"10429","DOI":"10.1523\/JNEUROSCI.18-24-10429.1998","article-title":"Neurite outgrowth stimulated by neural cell adhesion molecules requires growth\u2010associated protein\u201043 (GAP\u201043) function and is associated with GAP\u201043 phosphorylation in growth cones","volume":"18","author":"Meiri K.F.","year":"1998","journal-title":"J. Neurosci."},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2000952"},{"key":"e_1_2_6_50_1","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1523\/JNEUROSCI.09-04-01452.1989","article-title":"Rapid induction of the major embryonic alpha\u2010tubulin mRNA, T alpha 1, during nerve regeneration in adult rats","volume":"9","author":"Miller F.D.","year":"1989","journal-title":"J. Neurosci."},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)00598-Y"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-012-1416-6"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.05.033"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2009.08.010"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3609"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2009.04.031"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.04.028"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.12.030189.001015"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.89.1.96"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1996.tb00744.x"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(84)90030-X"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.08-09-03181.1988"},{"key":"e_1_2_6_63_1","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1523\/JNEUROSCI.09-04-01303.1989","article-title":"Axonal transport and localization of B\u201050\/GAP\u201043\u2010like immunoreactivity in regenerating sciatic and facial nerves of the rat","volume":"9","author":"Tetzlaff W.","year":"1989","journal-title":"J. Neurosci."},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.11-08-02528.1991"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.111.6.3035"},{"key":"e_1_2_6_66_1","first-page":"62","article-title":"gp130 cytokines are positive signals triggering changes in gene expression and axon outgrowth in peripheral neurons following injury","volume":"4","author":"Zigmond R.E.","year":"2011","journal-title":"Front. Mol. Neurosci."},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2012.08.017"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1995.74.6.2625"}],"container-title":["European Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fejn.13070","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejn.13070","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T00:59:47Z","timestamp":1696294787000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejn.13070"}},"subtitle":[],"editor":[{"given":"Doug","family":"Munoz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,11]]},"references-count":67,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2015,11]]}},"alternative-id":["10.1111\/ejn.13070"],"URL":"https:\/\/doi.org\/10.1111\/ejn.13070","archive":["Portico"],"relation":{},"ISSN":["0953-816X","1460-9568"],"issn-type":[{"value":"0953-816X","type":"print"},{"value":"1460-9568","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11]]},"assertion":[{"value":"2015-04-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-09-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-11-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}