Immunological myelin disruption does not alter expression of regeneration-associated genes in intact or axotomized rubrospinal neurons.
The inability of axotomized neurons to regenerate within the CNS has been partially attributed to a number of inhibitory factors associated with CNS myelin that are extrinsic to the severed neurons. However, some neurons are capable of limited regeneration after injury and this ability has been shown to correlate with the expression of certain regeneration-associated genes (RAGs) intrinsic to injured neurons. It has therefore been postulated that neutralization of inhibitory factors, as well as the induction of an appropriate neuronal cell body response, would facilitate improved regrowth of injured CNS axons. In previous studies we have shown that immunological removal of myelin from the spinal cord facilitates axonal regeneration by rubrospinal neurons, as indicated by retrograde transport of a fluorescent dye placed distal to the site of injury. Here, we investigated whether the immunological focal removal of spinal cord myelin, following a thoracic spinal cord injury, concomitantly stimulated an increase in the expression of RAGs in rubrospinal neurons. In situ hybridization for Talpha-1 tubulin and GAP-43 at days 7, 14, and 21 revealed no significant increase in gene expression in rubrospinal neurons following immunological demyelination. The ability of various neuronal populations to sprout or slowly regrow without expressing the previously characterized cell body response is reviewed. We conclude that the recently demonstrated regeneration of rubrospinal tract, after immunologically directed spinal cord demyelination, is the result of either axonal sprouting or slow axonal regrowth without the increased expression of RAGs characteristic for fast axon regeneration.
Hiebert
G W
GW
CORD (Collaboration On Repair Discoveries), c/o Biosciences Building, Department of Zoology, University of British Columbia, 6270 University Boulevard, Vancouver, British Columbia, V6T 1Z4, Canada.
Dyer
J K
JK
Tetzlaff
W
W
Steeves
J D
JD
D000818:Animals; D001369:Axons / Q000502:physiology; D019771:Axotomy; D019922:GAP-43 Protein / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000276:immunology*; D017403:In Situ Hybridization; D008297:Male; D009186:Myelin Sheath / Q000276:immunology* / Q000378:metabolism; D009416:Nerve Regeneration / Q000235:genetics* / Q000276:immunology*; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012012:Red Nucleus / Q000473:pathology / Q000503:physiopathology; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000276:immunology*; D013904:Thoracic Vertebrae; D014404:Tubulin / Q000096:biosynthesis / Q000235:genetics
D019922:GAP-43 Protein; D012333:RNA, Messenger; D014404:Tubulin