Chronic nerve compression injury induces a phenotypic switch of neurons within the dorsal root ganglia.
Chronic nerve compression (CNC) injury initiates a series of pathological changes within the peripheral nerve at the site of injury. However, to date, little work has been performed to explore neuronal cell body responses to CNC injury. Here we show a preferential upregulation of growth-associated protein-43 (GAP-43) and enhanced Fluoro Ruby uptake by the small-diameter calcitonin gene-related protein (CGRP) and isolectin B4 (IB4)-positive neurons in the L4 and L5 ipsilateral dorsal root ganglion (DRG) 2 weeks and 1 month post injury. Furthermore, L4 and L5 DRGs ipsilateral to CNC injury also demonstrated a marked reduction in neurofilament 200 (NF-200) neurons and an increase in CGRP and IB4 neurons at early time points. All numbers normalized to values comparable to those of control when the DRG was evaluated 6 months post injury. Quantification of glial-derived neurotrophic factor (GDNF) protein revealed an upregulation in L4 and L5 DRG followed by a return to baseline values at later stages following injury. Upregulation of GDNF expression by Schwann cells was also readily apparent with both immunohistochemistry and Western blot analysis of 1 month compressed sciatic nerve specimens. Thus, CNC induces a phenotypic change in the DRG that appears to be temporally associated with increases in GDNF protein expression at and near the site of the compression injury in the nerve.
Chao
Tom
T
Department of Orthopaedic Surgery, University of California, Irvine, Irvine, California 92697, USA.
Pham
Khoa
K
Steward
Oswald
O
Gupta
Ranjan
R
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D007839:Functional Laterality; D019922:GAP-43 Protein / Q000378:metabolism; D005727:Ganglia, Spinal / Q000473:pathology*; D005786:Gene Expression Regulation / Q000502:physiology*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008297:Male; D009408:Nerve Compression Syndromes / Q000150:complications / Q000473:pathology*; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000150:complications / Q000473:pathology*; D013266:Stilbamidines / Q000378:metabolism; D013997:Time Factors
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D019922:GAP-43 Protein; D051100:Glial Cell Line-Derived Neurotrophic Factor; D037102:Lectins; D016900:Neurofilament Proteins; D013266:Stilbamidines; C051774:neurofilament protein H; D015740:Calcitonin Gene-Related Peptide