Descrizione del progetto
Uno studio esamina i disturbi neurologici dell’avvelenamento da ciguatera
Le ciguatossine sono tossine presenti nei frutti di mare che derivano dal consumo di dinoflagellati o altri elementi tossici da parte dei pesci, e causano un tipo di intossicazione alimentare negli esseri umani chiamata ciguatera. I disturbi sensoriali specifici indotti dalla ciguatera suggeriscono che le ciguatossine attivino sottoinsiemi specifici di neuroni somatosensoriali primari o del corno dorsale. Finanziato dal programma di azioni Marie Skłodowska-Curie, il progetto SENSO-CIGUA si propone di studiare i marcatori molecolari dei neuroni sensoriali del corno dorsale primario e superficiale che rispondono alle ciguatossine e anche gli attori molecolari coinvolti nel prurito spontaneo e nell’allodinia da freddo causati da queste tossine.
Obiettivo
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.
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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
29238 BREST
Francia