Immunization with myelin or recombinant Nogo-66/MAG in alum promotes axon regeneration and sprouting after corticospinal tract lesions in the spinal cord.
We have shown previously that immunization with myelin in incomplete Freund's adjuvant (IFA) is able to promote robust regeneration of corticospinal tract fibers in adult mice. In the present study the effectiveness of such immunization with myelin was compared to that of a combination of two axon growth inhibitors in myelin, Nogo-66 (the 66-amino-acid inhibitory region of Nogo-A) and myelin-associated glycoprotein (MAG). The effectiveness of two adjuvants, IFA and aluminum hydroxide (Alum), was also compared, the latter being one that can be used in humans. In addition, larger dorsal overhemisections were made at the lower thoracic level, which resulted in a larger scar. These studies were carried out in SJL/J mice, a mouse strain that is susceptible to autoimmune experimental allergic encephalomyelitis (EAE). None of the immunized mice developed EAE. Long-distance axon regeneration and sprouting of the corticospinal tract was seen in myelin and Nogo-66/MAG immunized mice. Alum was as effective or better than IFA as the adjuvant. Overall, the robustness of axon growth and sprouting was greater in mice immunized with myelin. The abundance of this growth was less than in our earlier work in which smaller lesions were made, pointing to the possible influence of inhibitors in the scar. This work shows, however, that axon growth inhibitors in myelin can be selectively blocked using this immunization approach to promote long-distance axon regeneration in the spinal cord.
Sicotte
Maryline
M
Centre for Research in Neuroscience, McGill University Health Centre, Montreal General Hospital Research Institute, 1650 Cedar Avenue, Montreal, Quebec, Canada, H3G 1A4.
Tsatas
Ourania
O
Jeong
Suh Young
SY
Cai
Chuan-Qi
CQ
He
Zhigang
Z
David
Samuel
S
D000536:Aluminum Hydroxide / Q000494:pharmacology; D000818:Animals; D005260:Female; D005620:Freund's Adjuvant / Q000494:pharmacology; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D007167:Immunotherapy / Q000379:methods / Q000639:trends; D008055:Lipids; D051379:Mice; D008815:Mice, Inbred Strains; D009185:Myelin Proteins / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D009186:Myelin Sheath / Q000276:immunology* / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D009413:Nerve Fibers, Myelinated / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000235:genetics / Q000276:immunology*; D000070798:Nogo Proteins; D011712:Pyramidal Tracts / Q000187:drug effects / Q000254:growth & development / Q000293:injuries*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D016896:Treatment Outcome
D008055:Lipids; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D000070798:Nogo Proteins; C000603199:RTN4 protein, human; C000603201:Rtn4 protein, mouse; C114843:incomplete Freund's adjuvant; D000536:Aluminum Hydroxide; D005620:Freund's Adjuvant