Abstract
Ciguatoxins are polyether marine toxins that act as sodium channel activators. These toxins cause ciguatera, one of the most widespread nonbacterial forms of food poisoning, which presents several symptoms in humans including long-term neurological alterations. Earlier work has shown that both acute and chronic exposure of primary cortical neurons to synthetic ciguatoxin CTX3C have profound impacts on neuronal function. Thus, the present work aimed to identify relevant neuronal genes and metabolic pathways that could be altered by ciguatoxin exposure. To study the effect of ciguatoxins in primary neurons in culture, we performed a transcriptomic analysis using whole mouse genome microarrays, for primary cortical neurons exposed during 6, 24, or 72 h in culture to CTX3C. Here, we have shown that the effects of the toxin on gene expression differ with the exposure time. The results presented here have identified several relevant genes and pathways related to the effect of ciguatoxins on neurons and may assist in future research or even treatment of ciguatera. Moreover, we demonstrated that the effects of the toxin on gene expression were exclusively consequential of its action as a voltage-gated sodium channel activator, since all the effects of CTX3C were avoided by preincubation of the neurons with the sodium channel blocker tetrodotoxin.
Highlights
Ciguatoxins are polyether marine toxins known to activate voltage-gated sodium channels [1,2]and cause one of the most widespread forms of nonbacterial food poisoning, named ciguatera.Ciguatera fish poisoning is a seafood-borne illness caused by the consumption of fish contaminated with ciguatera toxins, produced by marine dinoflagellates of the genus Gambierdiscus
In the search for the cellular mechanisms underlying the long-lasting neurological changes produced by ciguatoxins in neurons, we have described that acute exposure of cortical neurons to the synthetic ciguatoxin CTX3C caused a rapid membrane depolarization and increased the amplitude of miniature inhibitory postsynaptic currents, whereas it decreased the amplitude of miniature excitatory postsynaptic currents
Since synthetic ciguatoxin CTX3C has been shown to have a profound effect on neuronal transmission in mice primary cortical neurons [14,17], here we aimed to identify the genes involved in the functional effects of ciguatoxins in neurons and their dependence on the sodium channel activation caused by the toxin
Summary
Ciguatera fish poisoning is a seafood-borne illness caused by the consumption of fish contaminated with ciguatera toxins, produced by marine dinoflagellates of the genus Gambierdiscus. Until recently, this food poisoning was endemic in several tropical and subtropical areas; its occurrence. In the search for the cellular mechanisms underlying the long-lasting neurological changes produced by ciguatoxins in neurons, we have described that acute exposure of cortical neurons to the synthetic ciguatoxin CTX3C caused a rapid membrane depolarization and increased the amplitude of miniature inhibitory postsynaptic currents (mIPSCs), whereas it decreased the amplitude of miniature excitatory postsynaptic currents (mEPSCs). In the same cellular model, we have demonstrated that a larger exposure (30 min) of cortical neurons to CTX3C produced a rapid upregulation of the immediate early genes Arc and Egr, which are known to be increased by neuronal activity and are implicated in the regulation of synaptic homeostasis [15,16]
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