C-fiber (Remak) bundles contain both isolectin B4-binding and calcitonin gene-related peptide-positive axons

Beth B Murinson, Paul Ned Hoffman, Michael Reza Banihashemi, Richard Meyer, John Wesley Griffin

Research output: Contribution to journalArticle

Abstract

Unmyelinated nerve fibers (Remak bundles) in the rodent sciatic nerve typically contain multiple axons. This study asked whether C-fiber bundles contain axons arising from more than one type of neuron. Most small neurons of the lumbar dorsal root ganglion (DRG) are either glial cell line-derived neurotrophic factor dependent or nerve growth factor dependent, binding either isolectin B4 (IB4) or antibodies to calcitonin gene-related peptide (CGRP), respectively. Injection of IB4-conjugated horseradish peroxidase into a lumbar DRG resulted in intense labeling of IB4 axons, with very low background. Visualized by confocal fluorescence, IB4-binding and CGRP-positive nerve fibers orginating from different DRG neurons came together and remained closely parallel over long distances, suggesting that these two types of axon occupy the same Remak bundle. With double-labeling immunogold electron microscopy (EM), we confirmed that IB4 and CGRP axons were distinct and were found together in single Remak bundles. Previous studies indicate that some DRG neurons express both CGRP and IB4 binding. To ensure that our immunogold results were not a consequence of coexpression, we studied large populations of unmyelinated axons by using quantitative single-label EM. Tetramethylbenzidine, a chromogen with strong intrinsic signal amplification of IB4-horseradish peroxidase, labeled as many as 52% of unmyelinated axons in the dorsal root. Concomitantly, 97% of the Remak bundles with more than one axon contained at least one IB4-labeled axon. Probabilistic modeling using binomial distribution functions rejected the hypothesis that IB4 axons segregate into IB4-specific bundles (P <0.00001). We conclude that most Remak bundle Schwann cells simultaneously support diverse axon types with different growth factor dependences.

Original languageEnglish (US)
Pages (from-to)392-402
Number of pages11
JournalJournal of Comparative Neurology
Volume484
Issue number4
DOIs
StatePublished - Apr 18 2005

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Unmyelinated Nerve Fibers
Calcitonin Gene-Related Peptide
Lectins
Axons
Spinal Ganglia
Neurons
Horseradish Peroxidase
Electron Microscopy
Binomial Distribution
Glial Cell Line-Derived Neurotrophic Factor
Spinal Nerve Roots
Schwann Cells
Nerve Growth Factor
Sciatic Nerve
Nerve Fibers
Rodentia
Intercellular Signaling Peptides and Proteins
Fluorescence

Keywords

  • C-fiber
  • Dorsal root
  • Dorsal root ganglion
  • Peripheral nerve
  • Unmyelinated axon

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

C-fiber (Remak) bundles contain both isolectin B4-binding and calcitonin gene-related peptide-positive axons. / Murinson, Beth B; Hoffman, Paul Ned; Banihashemi, Michael Reza; Meyer, Richard; Griffin, John Wesley.

In: Journal of Comparative Neurology, Vol. 484, No. 4, 18.04.2005, p. 392-402.

Research output: Contribution to journalArticle

Murinson, Beth B ; Hoffman, Paul Ned ; Banihashemi, Michael Reza ; Meyer, Richard ; Griffin, John Wesley. / C-fiber (Remak) bundles contain both isolectin B4-binding and calcitonin gene-related peptide-positive axons. In: Journal of Comparative Neurology. 2005 ; Vol. 484, No. 4. pp. 392-402.
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abstract = "Unmyelinated nerve fibers (Remak bundles) in the rodent sciatic nerve typically contain multiple axons. This study asked whether C-fiber bundles contain axons arising from more than one type of neuron. Most small neurons of the lumbar dorsal root ganglion (DRG) are either glial cell line-derived neurotrophic factor dependent or nerve growth factor dependent, binding either isolectin B4 (IB4) or antibodies to calcitonin gene-related peptide (CGRP), respectively. Injection of IB4-conjugated horseradish peroxidase into a lumbar DRG resulted in intense labeling of IB4 axons, with very low background. Visualized by confocal fluorescence, IB4-binding and CGRP-positive nerve fibers orginating from different DRG neurons came together and remained closely parallel over long distances, suggesting that these two types of axon occupy the same Remak bundle. With double-labeling immunogold electron microscopy (EM), we confirmed that IB4 and CGRP axons were distinct and were found together in single Remak bundles. Previous studies indicate that some DRG neurons express both CGRP and IB4 binding. To ensure that our immunogold results were not a consequence of coexpression, we studied large populations of unmyelinated axons by using quantitative single-label EM. Tetramethylbenzidine, a chromogen with strong intrinsic signal amplification of IB4-horseradish peroxidase, labeled as many as 52{\%} of unmyelinated axons in the dorsal root. Concomitantly, 97{\%} of the Remak bundles with more than one axon contained at least one IB4-labeled axon. Probabilistic modeling using binomial distribution functions rejected the hypothesis that IB4 axons segregate into IB4-specific bundles (P <0.00001). We conclude that most Remak bundle Schwann cells simultaneously support diverse axon types with different growth factor dependences.",
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T1 - C-fiber (Remak) bundles contain both isolectin B4-binding and calcitonin gene-related peptide-positive axons

AU - Murinson, Beth B

AU - Hoffman, Paul Ned

AU - Banihashemi, Michael Reza

AU - Meyer, Richard

AU - Griffin, John Wesley

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N2 - Unmyelinated nerve fibers (Remak bundles) in the rodent sciatic nerve typically contain multiple axons. This study asked whether C-fiber bundles contain axons arising from more than one type of neuron. Most small neurons of the lumbar dorsal root ganglion (DRG) are either glial cell line-derived neurotrophic factor dependent or nerve growth factor dependent, binding either isolectin B4 (IB4) or antibodies to calcitonin gene-related peptide (CGRP), respectively. Injection of IB4-conjugated horseradish peroxidase into a lumbar DRG resulted in intense labeling of IB4 axons, with very low background. Visualized by confocal fluorescence, IB4-binding and CGRP-positive nerve fibers orginating from different DRG neurons came together and remained closely parallel over long distances, suggesting that these two types of axon occupy the same Remak bundle. With double-labeling immunogold electron microscopy (EM), we confirmed that IB4 and CGRP axons were distinct and were found together in single Remak bundles. Previous studies indicate that some DRG neurons express both CGRP and IB4 binding. To ensure that our immunogold results were not a consequence of coexpression, we studied large populations of unmyelinated axons by using quantitative single-label EM. Tetramethylbenzidine, a chromogen with strong intrinsic signal amplification of IB4-horseradish peroxidase, labeled as many as 52% of unmyelinated axons in the dorsal root. Concomitantly, 97% of the Remak bundles with more than one axon contained at least one IB4-labeled axon. Probabilistic modeling using binomial distribution functions rejected the hypothesis that IB4 axons segregate into IB4-specific bundles (P <0.00001). We conclude that most Remak bundle Schwann cells simultaneously support diverse axon types with different growth factor dependences.

AB - Unmyelinated nerve fibers (Remak bundles) in the rodent sciatic nerve typically contain multiple axons. This study asked whether C-fiber bundles contain axons arising from more than one type of neuron. Most small neurons of the lumbar dorsal root ganglion (DRG) are either glial cell line-derived neurotrophic factor dependent or nerve growth factor dependent, binding either isolectin B4 (IB4) or antibodies to calcitonin gene-related peptide (CGRP), respectively. Injection of IB4-conjugated horseradish peroxidase into a lumbar DRG resulted in intense labeling of IB4 axons, with very low background. Visualized by confocal fluorescence, IB4-binding and CGRP-positive nerve fibers orginating from different DRG neurons came together and remained closely parallel over long distances, suggesting that these two types of axon occupy the same Remak bundle. With double-labeling immunogold electron microscopy (EM), we confirmed that IB4 and CGRP axons were distinct and were found together in single Remak bundles. Previous studies indicate that some DRG neurons express both CGRP and IB4 binding. To ensure that our immunogold results were not a consequence of coexpression, we studied large populations of unmyelinated axons by using quantitative single-label EM. Tetramethylbenzidine, a chromogen with strong intrinsic signal amplification of IB4-horseradish peroxidase, labeled as many as 52% of unmyelinated axons in the dorsal root. Concomitantly, 97% of the Remak bundles with more than one axon contained at least one IB4-labeled axon. Probabilistic modeling using binomial distribution functions rejected the hypothesis that IB4 axons segregate into IB4-specific bundles (P <0.00001). We conclude that most Remak bundle Schwann cells simultaneously support diverse axon types with different growth factor dependences.

KW - C-fiber

KW - Dorsal root

KW - Dorsal root ganglion

KW - Peripheral nerve

KW - Unmyelinated axon

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