Systemic deletion of the myelin-associated outgrowth inhibitor Nogo-A improves regenerative and plastic responses after spinal cord injury.
To investigate the role of the myelin-associated protein Nogo-A on axon sprouting and regeneration in the adult central nervous system (CNS), we generated Nogo-A-deficient mice. Nogo-A knockout (KO) mice were viable, fertile, and not obviously afflicted by major developmental or neurological disturbances. The shorter splice form Nogo-B was strongly upregulated in the CNS. The inhibitory effect of spinal cord extract for growing neurites was decreased in the KO mice. Two weeks following adult dorsal hemisection of the thoracic spinal cord, Nogo-A KO mice displayed more corticospinal tract (CST) fibers growing toward and into the lesion compared to their wild-type littermates. CST fibers caudal to the lesion-regenerating and/or sprouting from spared intact fibers-were also found to be more frequent in Nogo-A-deficient animals.
Simonen
Marjo
M
Brain Research Institute, University of Zurich, CH-8057, Zurich, Switzerland.
Pedersen
Vera
V
Weinmann
Oliver
O
Schnell
Lisa
L
Buss
Armin
A
Ledermann
Birgit
B
Christ
Franziska
F
Sansig
Gilles
G
van der Putten
Herman
H
Schwab
Martin E
ME
D017398:Alternative Splicing; D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis; D001522:Behavior, Animal; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002452:Cell Count; D002478:Cells, Cultured; D005328:Fetal Viability / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009185:Myelin Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000502:physiology / Q000648:ultrastructure; D009412:Nerve Fibers / Q000502:physiology / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D000070798:Nogo Proteins; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020127:Recovery of Function / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000235:genetics / Q000503:physiopathology*; D015854:Up-Regulation
D000954:Antigens, Surface; D009185:Myelin Proteins; D000070798:Nogo Proteins; D020033:Protein Isoforms; C000603201:Rtn4 protein, mouse; C000603197:Rtn4 protein, rat