Release of neuropeptides from a neuro-cutaneous co-culture model: a novel in vitro model for studying sensory effects of ciguatoxins

Le Garrec, Raphaele, L'herondelle, Killian, Le Gall-Ianotto, Christelle, Lebonvallet, Nicolas, Leschiera, Raphael, Buhe, Virginie, Talagas, Matthieu, Vetter, Irina, Lewis, Richard J. and Misery, Laurent (2016) Release of neuropeptides from a neuro-cutaneous co-culture model: a novel in vitro model for studying sensory effects of ciguatoxins. Toxicon, 116 4-10. doi:10.1016/j.toxicon.2015.11.004

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Author Le Garrec, Raphaele
L'herondelle, Killian
Le Gall-Ianotto, Christelle
Lebonvallet, Nicolas
Leschiera, Raphael
Buhe, Virginie
Talagas, Matthieu
Vetter, Irina
Lewis, Richard J.
Misery, Laurent
Title Release of neuropeptides from a neuro-cutaneous co-culture model: a novel in vitro model for studying sensory effects of ciguatoxins
Formatted title
Release of neuropeptides from a neuro-cutaneous co-culture model: a novel in vitro model for studying sensory effects of ciguatoxins
Journal name Toxicon   Check publisher's open access policy
ISSN 1879-3150
0041-0101
Publication date 2016-06-15
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.toxicon.2015.11.004
Open Access Status File (Author Post-print)
Volume 116
Start page 4
End page 10
Total pages 7
Place of publication Kidlington, Oxford, United Kingdom
Publisher Elsevier
Language eng
Formatted abstract
Ciguatoxins are the major toxins responsible for ciguatera fish poisoning, a disease dominated by muco-cutaneous sensory disorders including paresthesiae, cold dysesthesia and pruritus. While the ciguatoxins are well known to target voltage-gated sodium channels (VGSCs), the ensuing molecular mechanisms underlying these sensory disorders remain poorly understood. In this study, we propose a primary sensory neuron-keratinocyte co-culture as an appropriate model to study the neuro-cutaneous effects of ciguatoxins. Using this model, we show for the first time that nanomolar concentrations of Pacific ciguatoxin-2 (P-CTX-2) induced a VGSC-dependent release of substance P (SP) and calcitonin gene-related peptide (CGRP). As these neuropeptides are known mediators of pain and itch sensations, the ciguatoxin-induced sensory disturbances in ciguatera fish poisoning may involve the release of these neuropeptides. We further determined time- and P-CTX-2 concentration-dependence of the release of SP and CGRP from the co-culture model. Moreover, we highlighted the influence of extracellular calcium on the release of neuropeptides elicited by P-CTX-2. These findings underline the usefulness of this novel in vitro model for studying the cellular and molecular mechanisms of the neuro-cutaneous effects of ciguatoxins, which may assist with identifying potential therapeutics for ciguatera fish poisoning.
Keyword Ciguatoxins
In vitro model
Neuropeptide release
Sensory disorders
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
 
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