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Release of neuropeptides from a neuro-cutaneous co-culture model: a novel in vitro model for studying sensory effects of ciguatoxins
Le Garrec, R.; L'herondelle, K.; Le Gall-Ianotto, C.; Lebonvallet, N.; Leschiera, R.; Buhe, V.; Talagas, M.; Vetter, I.; Lewis, R.J.; Misery, L. (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. https://dx.doi.org/10.1016/j.toxicon.2015.11.004
In: Toxicon. Elsevier: Oxford. ISSN 0041-0101; e-ISSN 1879-3150, meer
Peer reviewed article  
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    Marien/Kust
Author keywords
    Ciguatoxins Sensory disorders Neuropeptide release In vitro model
Auteurs  Top 
  • Le Garrec, R.
  • L'herondelle, K.
  • Le Gall-Ianotto, C.
  • Lebonvallet, N.
  • Leschiera, R.
  • Buhe, V.
  • Talagas, M.
  • Vetter, I.
  • Lewis, R.J.
  • Misery, L.
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.
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