title: Reduced expression of regeneration associated genes in chronically axotomized facial motoneurons.
abstract: Chronically axotomized motoneurons progressively fail to regenerate their axons. Since axonal regeneration is associated with the increased expression of tubulin, actin and GAP-43, we examined whether the regenerative failure is due to failure of chronically axotomized motoneurons to express and sustain the expression of these regeneration associated genes (RAGs). Chronically axotomized facial motoneurons were subjected to a second axotomy to mimic the clinical surgical procedure of refreshing the proximal nerve stump prior to nerve repair. Expression of α1-tubulin, actin and GAP-43 was analyzed in axotomized motoneurons using in situ hybridization followed by autoradiography and silver grain quantification. The expression of these RAGs by acutely axotomized motoneurons declined over several months. The chronically injured motoneurons responded to a refreshment axotomy with a re-increase in RAG expression. However, this response to a refreshment axotomy of chronically injured facial motoneurons was less than that seen in acutely axotomized facial motoneurons. These data demonstrate that the neuronal RAG expression can be induced by injury-related signals and does not require acute deprivation of target derived factors. The transient expression is consistent with a transient inflammatory response to the injury. We conclude that transient RAG expression in chronically axotomized motoneurons and the weak response of the chronically axotomized motoneurons to a refreshment axotomy provides a plausible explanation for the progressive decline in regenerative capacity of chronically axotomized motoneurons.
authors.affiliation: Department of Neuroscience, University of Alberta, Edmonton, AB T6G 2S2, Canada; ICORD (International Collaboration on Repair Discoveries), Canada; Department Zoology, University of British Columbia, Vancouver, V5Z 1M9, BC, Canada; Department Surgery, University of British Columbia, Vancouver, BC, Canada. Electronic address: tessat.gordon@gmail.com.
authors.forename: T
authors.initials: T
authors.lastname: Gordon
authors.affiliation: Department of Neuroscience, University of Alberta, Edmonton, AB T6G 2S2, Canada; ICORD (International Collaboration on Repair Discoveries), Canada; Department Zoology, University of British Columbia, Vancouver, V5Z 1M9, BC, Canada; Department Surgery, University of British Columbia, Vancouver, BC, Canada.
authors.forename: S
authors.initials: S
authors.lastname: You
authors.affiliation: Department of Neuroscience, University of Alberta, Edmonton, AB T6G 2S2, Canada; ICORD (International Collaboration on Repair Discoveries), Canada; Department Zoology, University of British Columbia, Vancouver, V5Z 1M9, BC, Canada; Department Surgery, University of British Columbia, Vancouver, BC, Canada.
authors.forename: S L
authors.initials: SL
authors.lastname: Cassar
authors.affiliation: Department of Neuroscience, University of Alberta, Edmonton, AB T6G 2S2, Canada; ICORD (International Collaboration on Repair Discoveries), Canada; Department Zoology, University of British Columbia, Vancouver, V5Z 1M9, BC, Canada; Department Surgery, University of British Columbia, Vancouver, BC, Canada. Electronic address: tetzlaff@icord.org.
authors.forename: W
authors.initials: W
authors.lastname: Tetzlaff
mesh_terms: D000818:Animals; D019771:Axotomy; D004195:Disease Models, Animal; D005155:Facial Nerve Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009416:Nerve Regeneration / Q000502:physiology*; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*
chemical_list: D019922:GAP-43 Protein; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D014404:Tubulin; C061195:neurofilament protein M
keywords: Actin; Axotomy; GAP-43; Motoneuron; Neurofilament; Regeneration associated genes; Tubulin