title: Regeneration-associated genes decline in chronically injured rat sciatic motoneurons.
abstract: 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-associated 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 α1-tubulin, actin and GAP-43 mRNA was analysed in axotomized sciatic motoneurons by the use of in situ hybridization followed by autoradiography and silver grain quantification. The expression of these regeneration-associated genes by naive (acutely) axotomized motoneurons declined exponentially, to reach baseline levels within 6 months. 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-associated 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.
authors.affiliation: Neuroscience and Mental Health Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, T6G 2S2, Canada.|Department of Surgery, Division of Plastic Reconstructive Surgery, 5549A The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
authors.forename: Tessa
authors.initials: T
authors.lastname: Gordon
authors.affiliation: ICORD (International Collaboration on Repair Discoveries), Blusson Spinal Cord Centre, 818 W. 10th Avenue, Vancouver, BC, V5Z 1M9, Canada.|Departments of Zoology and Surgery, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Tetzlaff
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D019771:Axotomy; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism*; D009416:Nerve Regeneration; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000235:genetics* / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000199:Actins; D019922:GAP-43 Protein; D012333:RNA, Messenger; D014404:Tubulin
keywords: GAP-43; actin; axotomy; chronic nerve injury; motoneuron; tubulin