Both positive and negative factors regulate gene expression following chronic facial nerve resection.
Previously, we reported that following a chronic nerve resection, removal of the neuroma reversed the atrophy, increased the number of countable motoneurons and resulted in the re-expression of GAP-43 and alpha tubulin mRNA. In the present study, we questioned whether this response was due to the removal of the neuroma, or a result of factors such as neurotrophins, produced at the injury site. To test this hypothesis, 10 weeks after axotomy, the axonal transport blocker colchicine or, glial derived neurotrophic factor (GDNF) was injected proximal to the neuroma. The injection of GDNF or colchicine elicited an increase in motoneuron size and in GAP-43, but not alpha tubulin, mRNA. These data suggest that in addition to factors produced at the injury site, the neuroma acts as a source of target-like repressive signals that when removed results in an increase in gene expression and motoneuron size. To analyze the regenerative potential of chronically resected motoneurons, mice without a previous nerve injury and mice with a chronic resection received a pre-degenerated segment of sciatic nerve attached to the proximal facial nerve stump. Axons from both the chronic and acute groups grew into the grafts, however, significantly more retrogradely labeled motoneurons were counted in the acute group compared to the chronic resection group. No difference in motoneuron cell size was observed between the two groups of regenerated neurons. Therefore, despite severe atrophy, many of the surviving mouse facial motoneurons retain the propensity to extend their axons when provided with the appropriate environment.
McPhail
Lowell T
LT
ICORD (International Collaboration On Repair Discoveries), University of British Columbia, Rm 2465 Biosciences Building, 6270 University Boulevard, Vancouver, BC, Canada V6T1Z4.
Oschipok
Loren W
LW
Liu
Jie
J
Tetzlaff
Wolfram
W
D000818:Animals; D019771:Axotomy / Q000379:methods; D002452:Cell Count / Q000379:methods; D048429:Cell Size; D003078:Colchicine / Q000494:pharmacology; D020220:Facial Nerve Injuries / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007839:Functional Laterality / Q000502:physiology; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009414:Nerve Growth Factors / Q000494:pharmacology; D009463:Neuroma / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D016378:Tissue Transplantation / Q000379:methods; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
D019922:GAP-43 Protein; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D014404:Tubulin; D003078:Colchicine