Dataset Information

Transcriptomic Analysis of Ciguatoxin-Induced Changes in Gene Expression in Primary Cultures of Mice Cortical Neurons.

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.

SUBMITTER: Rubiolo JA

PROVIDER: S-EPMC5983248 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Transcriptomic Analysis of Ciguatoxin-Induced Changes in Gene Expression in Primary Cultures of Mice Cortical Neurons.

Rubiolo Juan Andrés JA Vale Carmen C Boente-Juncal Andrea A Hirama Masahiro M Yamashita Shuji S Camiña Mercedes M Vieytes Mercedes R MR Botana Luis M LM

Toxins 20180510 5

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 metabol ...[more]

PMID: 29748486

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Project description:Simple Summary When neurons are activated, two waves of gene expression changes occur to achieve neuronal adaptation to their environment. Currently, little is known about the changes in post-transcriptional modifications of neuronal transcripts in response to environmental stimuli. This study aims to investigate the dynamics of m5C modification on neuronal mRNAs upon depolarization using potassium chloride. We found that neuronal mRNAs carrying m5C modifications are enriched for genes with important neuronal functions. The numbers of m5C sites and methylated transcripts increased at 2 h after neuronal depolarization and slightly dropped at 6 h. Interestingly, for differentially methylated genes, a negative correlation between the levels of gene expression and RNA methylation is more prevalent. We anticipate our findings may shed new lights on post-transcriptional regulation in activated neurons, and the transcriptomic plus epi-transcriptomic datasets generated in this study would provide a valuable resource to the scientific community. Abstract Neuronal activity is accomplished via substantial changes in gene expression, which may be accompanied by post-transcriptional modifications including RNA cytosine-5 methylation (m5C). Despite several reports on the transcriptome profiling of activated neurons, the dynamics of neuronal mRNA m5C modification in response to environmental stimuli has not been explored. Here, we provide transcriptome-wide maps of m5C modification, together with gene expression profiles, for mouse cortical neurons at 0 h, 2 h, and 6 h upon membrane depolarization. Thousands of differentially expressed genes (DEGs) were identified during the neuronal depolarization process. In stimulated neurons, the majority of early response genes were found to serve as expression regulators of late response genes, which are involved in signaling pathways and diverse synaptic functions. With RNA bisulfite sequencing data, a union set of 439 m5C sites was identified with high confidence, and approximately 30% of them were shared by neurons at all three time points. Interestingly, over 41% of the m5C sites showed increased methylation upon neuronal activation and were enriched in transcripts coding for proteins with synaptic functions. In addition, a modest negative correlation was observed between RNA expression and methylation. In summary, our study provided dynamic transcriptome-wide landscapes of RNA m5C methylation in neurons, and revealed that mRNA m5C methylation is associated with the regulation of gene expression.

Dataset Information

Transcriptomic Analysis of Ciguatoxin-Induced Changes in Gene Expression in Primary Cultures of Mice Cortical Neurons.

Publications

Transcriptomic Analysis of Ciguatoxin-Induced Changes in Gene Expression in Primary Cultures of Mice Cortical Neurons.

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