Topographically specific regeneration of sensory axons in the spinal cord.
Artemin, a member of the glial-derived neurotrophic factor family, promotes robust regeneration of sensory axons after dorsal root crush. We report here that several classes of sensory axons regenerate to topographically appropriate regions of the dorsal horn with artemin treatment. Projections of regenerated muscle and cutaneous myelinated sensory afferents are restricted to the correct spinal segments and to appropriate regions within spinal gray matter. Regenerated unmyelinated axons expressing calcitonin gene-related peptide project only to superficial laminae of the dorsal horn, where uninjured nociceptive afferents project normally. In contrast, intraventricular infusion of a soluble form of the Nogo receptor that blocks the action of several myelin-associated inhibitory proteins promotes relatively unrestricted regeneration of sensory axons throughout the dorsal white and gray matter of the spinal cord. These results demonstrate that cues capable of guiding regenerating axons to appropriate spinal targets persist in the adult mammalian cord, but only some methods of stimulating regeneration allow the use of these cues by growing axons.
Department of Physiology, Tufts University School of Medicine, Boston, MA 02111, USA.
Pamela
P
Harvey
Bangjian
B
Gong
Anthony J
AJ
Rossomando
Eric
E
Frank
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000502:physiology*; D002490:Central Nervous System / Q000502:physiology; D058851:GPI-Linked Proteins; D005727:Ganglia, Spinal / Q000378:metabolism; D005786:Gene Expression Regulation; D008297:Male; D008954:Models, Biological; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000378:metabolism; D009416:Nerve Regeneration / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000070816:Nogo Receptor 1; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide / Q000378:metabolism*; D012038:Regeneration; D013116:Spinal Cord / Q000502:physiology*
C490887:Artn protein, rat; D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; C486581:Rtn4r protein, rat