title: Neurotrophin selectivity in organizing topographic regeneration of nociceptive afferents.
abstract: Neurotrophins represent some of the best candidates to enhance regeneration. In the current study, we investigated the effects of artemin, a member of the glial derived neurotrophic factor (GDNF) family, on sensory axon regeneration following a lumbar dorsal root injury and compared these effects with that observed after either NGF or GDNF expression in the rat spinal cord. Unlike previously published data, artemin failed to induce regeneration of large-diameter myelinated sensory afferents when expressed within either the spinal cord or DRG. However, artemin or NGF induced regeneration of calcitonin gene related peptide positive (CGRP(+)) axons only when expressed within the spinal cord. Accordingly, artemin or NGF enhanced recovery of only nociceptive behavior and showed a cFos distribution similar to the topography of regenerating axons. Artemin and GDNF signaling requires binding to different co-receptors (GFRα3 or GFRα1, respectively) prior to binding to the signaling receptor, cRet. Approximately 70% of DRG neurons express cRet, but only 35% express either co-receptor. To enhance artemin-induced regeneration, we co-expressed artemin with either GFRα3 or GDNF. Co-expression of artemin and GFRα3 only slightly enhanced regeneration of IB4(+) non-peptidergic nociceptive axons, but not myelinated axons. Interestingly, this co-expression also disrupted the ability of artemin to produce topographic targeting and lead to significant increases in cFos immunoreactivity within the deep dorsal laminae. This study failed to demonstrate artemin-induced regeneration of myelinated axons, even with co-expression of GFRα3, which only promoted mistargeted regeneration.
authors.affiliation: Shriners Hospitals Pediatric Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Kelamangalath
authors.affiliation: Shriners Hospitals Pediatric Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Tang
authors.affiliation: Shriners Hospitals Pediatric Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Bezik
authors.affiliation: Shriners Hospitals Pediatric Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Noelle
authors.initials: N
authors.lastname: Sterling
authors.affiliation: Shriners Hospitals Pediatric Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Son
authors.affiliation: Shriners Hospitals Pediatric Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA. Electronic address: george.smith@temple.edu.
authors.forename: George M
authors.initials: GM
authors.lastname: Smith
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000344:Afferent Pathways / Q000473:pathology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism; D006930:Hyperalgesia / Q000503:physiopathology; D037102:Lectins / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009619:Nociceptors / Q000378:metabolism*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D059348:Peripheral Nerve Injuries / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014161:Transduction, Genetic
chemical_list: D000276:Adjuvants, Immunologic; C490887:Artn protein, rat; D037102:Lectins; D009419:Nerve Tissue Proteins; D002772:Cholera Toxin; D020932:Nerve Growth Factor; D015740:Calcitonin Gene-Related Peptide
keywords: Artemin; Axonal guidance; Regeneration; Sensory system