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Neurobiology of sensory disturbances induced by ciguatoxins

Description du projet

Une étude examine les perturbations neurologiques de l’intoxication par la ciguatera

Les ciguatoxines sont des toxines présentes dans les fruits de mer qui proviennent de la consommation de dinoflagellés ou d’autres éléments toxiques par les poissons. Elles provoquent chez l’homme un type d’intoxication alimentaire appelé ciguatera. Les perturbations sensorielles spécifiques induites par la ciguatera suggèrent que les ciguatoxines activent des sous-ensembles spécifiques de neurones somatosensoriels primaires ou appartenant à la corne dorsale. Financé par le programme Actions Marie Skłodowska-Curie, le projet SENSO-CIGUA a l’intention d’étudier les marqueurs moléculaires des neurones sensoriels primaires et superficiels de la corne dorsale répondant aux ciguatoxines, ainsi que les acteurs moléculaires impliqués dans les démangeaisons spontanées et l’allodynie au froid provoquées par ces toxines.

Objectif

The IF-GF project aims to decipher in vivo the neurobiology of sensory disturbances induced by ciguatoxins (CTXs), which cause ciguatera fish poisoning and have recently become a European food safety concern as emerging toxins. CTXs are the most potent known activators of voltage-gated sodium channels, without isoform specificity. The strong predominance of specific sensory disturbances in ciguatera suggests that CTXs activate specific subsets of primary and/or dorsal horn somatosensory neurons, which is consistent with the population coding theory. The first specific objective is to characterize the molecular markers of primary and superficial dorsal horn (SDH) sensory neurons responding to CTXs and the molecular players involved in the CTX-induced spontaneous itch and cold allodynia. Next, the planned action aims to examine the role of sensitization of sensory receptors and channels in the sensations evoked, and to identify the mediators and mechanisms involved. To achieve this, the methods used will combine a behavioural test capable of distinguishing between scratching and pain behaviours, functional methods including in vivo electrophysiological recordings in SDH neurons and calcium imaging in primary neurons, and a variety of tools comprising neurotoxic ablation, genetic invalidation, and chemogenetic inhibition of specific neuronal subpopulations. These approaches, still used by a few teams around the world to explore neural circuits, are an outstanding opportunity to advance research on sensory disorders induced by CTXs. In addition, using CTXs as singular tools, the action has the potential to uniquely complement research on itch and pain neurobiology. The fellow will benefit from the world-renowned expertise and experience of the partner laboratory (at UC Davis, USA) to acquire new technical skills and knowledge essential for her future career, and from its international network to broaden her prospects for research collaboration.

Coordinateur

UNIVERSITE DE BRETAGNE OCCIDENTALE
Contribution nette de l'UE
€ 153 109,92
Adresse
RUE MATTHIEU GALLOU 3
29238 BREST
France

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Région
Bretagne Bretagne Finistère
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
€ 153 109,92

Partenaires (1)