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 p artially attributed to a number of inhibitory factors associated with CNS m yelin that are extrinsic to the severed neurons. However, some neurons are capable of limited regeneration after injury and this ability has been show n 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 appro priate neuronal cell body response, would facilitate improved regrowth of i njured CNS axons. In previous studies we have shown that immunological remo val of myelin from the spinal cord facilitates axonal regeneration by rubro spinal neurons, as indicated by retrograde transport of a fluorescent dye p laced distal to the site of injury. Here, we investigated whether the immun ological focal removal of spinal cord myelin, following a thoracic spinal c ord injury, concomitantly stimulated an increase in the expression of RAGs in rubrospinal neurons. In situ hybridization for T alpha-1 tubulin and GAP -43 at days 7, 14, and 21 revealed no significant increase in gene expressi on in rubrospinal neurons following immunological demyelination. The abilit y of various neuronal populations to sprout or slowly regrow without expres sing the previously characterized cell body response is reviewed. We conclu de 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. (C) 2000 Academic Press.