Melanocortin-4 receptor expression in different classes of spinal and vagal primary afferent neurons in the mouse

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Melanocortin-4 receptor (MC4R) ligands are known to modulate nociception, but the site of action of MC4R signaling on nociception remains to be elucidated. The current study investigated MC4R expression in dorsal root ganglia (DRG) of the MC4R-GFP reporter mouse. Because MC4R is known to be expressed in vagal afferent neurons in the nodose ganglion (NG), we also systematically compared MC4R-expressing vagal and spinal afferent neurons. Abundant green fluorescent protein (GFP) immunoreactivity was found in about 45% of DRG neuronal profiles (at the mid-thoracic level), the majority being small-sized profiles. Immunohistochemistry combined with in situ hybridization confirmed that GFP was genuinely produced in MC4R-expressing neurons in the DRG. While a large number of GFP profiles in the DRG coexpressed Nav1.8 mRNA (84%) and bound isolectin B4 (72%), relatively few GFP profiles were positive for NF200 (16%) or CGRP (13%), suggesting preferential MC4R expression in C-fiber nonpeptidergic neurons. By contrast, GFP in the NG frequently colocalized with Nav1.8 mRNA (64%) and NF200 (29%), but only to a moderate extent with isolectin B4 (16%). Lastly, very few GFP profiles in the NG expressed CGRP (5%) or CART (4%). Together, our findings demonstrate variegated MC4R expression in different classes of vagal and spinal primary afferent neurons, and underscore the role of the melanocortin system in modulating nociceptive and nonnociceptive peripheral sensory modalities.

Original languageEnglish (US)
Pages (from-to)3933-3948
Number of pages16
JournalJournal of Comparative Neurology
Volume520
Issue number17
DOIs
StatePublished - Dec 1 2012

Fingerprint

Receptor, Melanocortin, Type 4
Afferent Neurons
Green Fluorescent Proteins
Spinal Ganglia
Nodose Ganglion
Nociception
Lectins
Melanocortins
Neurons
Unmyelinated Nerve Fibers
Messenger RNA
In Situ Hybridization
Thorax
Immunohistochemistry
Ligands

Keywords

  • Dorsal root ganglion
  • Green fluorescent protein
  • Neuropeptide
  • Nociceptor
  • Nodose ganglion
  • Vagus nerve

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

@article{c27d9b3e88af46d8a3d71608b6f93ca9,
title = "Melanocortin-4 receptor expression in different classes of spinal and vagal primary afferent neurons in the mouse",
abstract = "Melanocortin-4 receptor (MC4R) ligands are known to modulate nociception, but the site of action of MC4R signaling on nociception remains to be elucidated. The current study investigated MC4R expression in dorsal root ganglia (DRG) of the MC4R-GFP reporter mouse. Because MC4R is known to be expressed in vagal afferent neurons in the nodose ganglion (NG), we also systematically compared MC4R-expressing vagal and spinal afferent neurons. Abundant green fluorescent protein (GFP) immunoreactivity was found in about 45{\%} of DRG neuronal profiles (at the mid-thoracic level), the majority being small-sized profiles. Immunohistochemistry combined with in situ hybridization confirmed that GFP was genuinely produced in MC4R-expressing neurons in the DRG. While a large number of GFP profiles in the DRG coexpressed Nav1.8 mRNA (84{\%}) and bound isolectin B4 (72{\%}), relatively few GFP profiles were positive for NF200 (16{\%}) or CGRP (13{\%}), suggesting preferential MC4R expression in C-fiber nonpeptidergic neurons. By contrast, GFP in the NG frequently colocalized with Nav1.8 mRNA (64{\%}) and NF200 (29{\%}), but only to a moderate extent with isolectin B4 (16{\%}). Lastly, very few GFP profiles in the NG expressed CGRP (5{\%}) or CART (4{\%}). Together, our findings demonstrate variegated MC4R expression in different classes of vagal and spinal primary afferent neurons, and underscore the role of the melanocortin system in modulating nociceptive and nonnociceptive peripheral sensory modalities.",
keywords = "Dorsal root ganglion, Green fluorescent protein, Neuropeptide, Nociceptor, Nodose ganglion, Vagus nerve",
author = "Laurent Gautron and Lee, {Charlotte E.} and Syann Lee and Elmquist, {Joel K.}",
year = "2012",
month = "12",
day = "1",
doi = "10.1002/cne.23137",
language = "English (US)",
volume = "520",
pages = "3933--3948",
journal = "Journal of Comparative Neurology",
issn = "0021-9967",
publisher = "Wiley-Liss Inc.",
number = "17",

}

TY - JOUR

T1 - Melanocortin-4 receptor expression in different classes of spinal and vagal primary afferent neurons in the mouse

AU - Gautron, Laurent

AU - Lee, Charlotte E.

AU - Lee, Syann

AU - Elmquist, Joel K.

PY - 2012/12/1

Y1 - 2012/12/1

N2 - Melanocortin-4 receptor (MC4R) ligands are known to modulate nociception, but the site of action of MC4R signaling on nociception remains to be elucidated. The current study investigated MC4R expression in dorsal root ganglia (DRG) of the MC4R-GFP reporter mouse. Because MC4R is known to be expressed in vagal afferent neurons in the nodose ganglion (NG), we also systematically compared MC4R-expressing vagal and spinal afferent neurons. Abundant green fluorescent protein (GFP) immunoreactivity was found in about 45% of DRG neuronal profiles (at the mid-thoracic level), the majority being small-sized profiles. Immunohistochemistry combined with in situ hybridization confirmed that GFP was genuinely produced in MC4R-expressing neurons in the DRG. While a large number of GFP profiles in the DRG coexpressed Nav1.8 mRNA (84%) and bound isolectin B4 (72%), relatively few GFP profiles were positive for NF200 (16%) or CGRP (13%), suggesting preferential MC4R expression in C-fiber nonpeptidergic neurons. By contrast, GFP in the NG frequently colocalized with Nav1.8 mRNA (64%) and NF200 (29%), but only to a moderate extent with isolectin B4 (16%). Lastly, very few GFP profiles in the NG expressed CGRP (5%) or CART (4%). Together, our findings demonstrate variegated MC4R expression in different classes of vagal and spinal primary afferent neurons, and underscore the role of the melanocortin system in modulating nociceptive and nonnociceptive peripheral sensory modalities.

AB - Melanocortin-4 receptor (MC4R) ligands are known to modulate nociception, but the site of action of MC4R signaling on nociception remains to be elucidated. The current study investigated MC4R expression in dorsal root ganglia (DRG) of the MC4R-GFP reporter mouse. Because MC4R is known to be expressed in vagal afferent neurons in the nodose ganglion (NG), we also systematically compared MC4R-expressing vagal and spinal afferent neurons. Abundant green fluorescent protein (GFP) immunoreactivity was found in about 45% of DRG neuronal profiles (at the mid-thoracic level), the majority being small-sized profiles. Immunohistochemistry combined with in situ hybridization confirmed that GFP was genuinely produced in MC4R-expressing neurons in the DRG. While a large number of GFP profiles in the DRG coexpressed Nav1.8 mRNA (84%) and bound isolectin B4 (72%), relatively few GFP profiles were positive for NF200 (16%) or CGRP (13%), suggesting preferential MC4R expression in C-fiber nonpeptidergic neurons. By contrast, GFP in the NG frequently colocalized with Nav1.8 mRNA (64%) and NF200 (29%), but only to a moderate extent with isolectin B4 (16%). Lastly, very few GFP profiles in the NG expressed CGRP (5%) or CART (4%). Together, our findings demonstrate variegated MC4R expression in different classes of vagal and spinal primary afferent neurons, and underscore the role of the melanocortin system in modulating nociceptive and nonnociceptive peripheral sensory modalities.

KW - Dorsal root ganglion

KW - Green fluorescent protein

KW - Neuropeptide

KW - Nociceptor

KW - Nodose ganglion

KW - Vagus nerve

UR - http://www.scopus.com/inward/record.url?scp=84867136887&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867136887&partnerID=8YFLogxK

U2 - 10.1002/cne.23137

DO - 10.1002/cne.23137

M3 - Article

C2 - 22592759

AN - SCOPUS:84867136887

VL - 520

SP - 3933

EP - 3948

JO - Journal of Comparative Neurology

JF - Journal of Comparative Neurology

SN - 0021-9967

IS - 17

ER -