Neurotrophin selectivity in organizing topographic regeneration of nociceptive afferents
| Autor: | Lakshmi Kelamangalath, George M. Smith, Young-Jin Son, Xiaoqing Tang, Noelle A. Sterling, Kathleen Bezik |
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| Rok vydání: | 2015 |
| Předmět: |
Pain Threshold
Cholera Toxin Calcitonin Gene-Related Peptide Artemin Nerve Tissue Proteins Article Rats Sprague-Dawley Adjuvants Immunologic Developmental Neuroscience Peripheral Nerve Injuries Transduction Genetic Ganglia Spinal Lectins Nerve Growth Factor Glial cell line-derived neurotrophic factor medicine Animals Axon Pain Measurement Afferent Pathways biology Chemistry Regeneration (biology) Nociceptors Spinal cord Nerve Regeneration Rats Disease Models Animal medicine.anatomical_structure Nerve growth factor nervous system Neurology Hyperalgesia biology.protein Nociceptor Female Neuroscience Psychomotor Performance Neurotrophin |
| Zdroj: | Experimental Neurology. 271:262-278 |
| ISSN: | 0014-4886 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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