Dataset Information

Corazonin Neurons Contribute to Dimorphic Ethanol Sedation Sensitivity in Drosophila melanogaster.

ABSTRACT: Exposure to alcohol has multiple effects on nervous system function, and organisms have evolved mechanisms to optimally respond to the presence of ethanol. Sex differences in ethanol-induced behaviors have been observed in several organisms, ranging from humans to invertebrates. However, the molecular mechanisms underlying the dimorphic regulation of ethanol-induced behaviors remain incompletely understood. Here, we observed sex differences in ethanol sedation sensitivity in Drosophila Genome Reference Panel (DGRP) lines of Drosophila melanogaster compared to the absence of dimorphism in standard laboratory wildtype and control lines. However, in dose response experiments, we were able to unmask dimorphic responses for the control mutant line w ¹¹¹⁸ by lowering the testing ethanol concentration. Notably, feminization of the small population of Corazonin (Crz) neurons in males was sufficient to induce female-like sedation sensitivity. We also tested the role of the transcription factor apontic (apt) based on its known expression in Crz neurons and its regulation of sedation responses. Interestingly, loss of function apt mutations increased sedation times in both males and females as compared to controls. No significant difference between male and female apt mutants was observed, suggesting a possible role of apt in the regulation of dimorphic ethanol-induced responses. Thus, our results shed light into the mechanisms regulating sex-differences in ethanol-induced behaviors at the cellular and molecular level, suggesting that the genetic sex in a small neuronal population plays an important role in modulating sex differences in behavioral responses to ethanol.

SUBMITTER: Oyeyinka A

PROVIDER: S-EPMC9256964 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Chloride intracellular channels (CLICs) are a unique family of evolutionarily conserved metamorphic proteins, switching between stable conformations based on redox conditions. CLICs have been implicated in a wide variety biological processes including ion channel activity, apoptosis, membrane trafficking, and enzymatic oxidoreductase activity. Understanding the molecular mechanisms by which CLICs engage in these activities is an area of active research. Here, the sole Drosophila melanogaster ortholog, Clic, was targeted for RNAi knockdown to identify genes and biological processes associated with Clic expression. Clic knockdown had a substantial impact on global transcription, altering expression of over 9% of transcribed Drosophila genes. Overrepresentation analysis of differentially expressed genes identified enrichment of 23 Gene Ontology terms including Cytoplasmic Translation, Oxidation-Reduction Process, Heme Binding, Membrane, Cell Junction, and Nucleolus. The top term, Cytoplasmic Translation, was enriched almost exclusively with downregulated genes. Drosophila Clic and vertebrate ortholog Clic4 have previously been tied to ethanol sensitivity and ethanol-regulated expression. Clic knockdown-responsive genes from the present study were found to overlap significantly with gene sets from 4 independently published studies related to ethanol exposure and sensitivity in Drosophila. Bioinformatic analysis of genes shared between these studies revealed an enrichment of genes related to amino acid metabolism, protein processing, oxidation-reduction processes, and lipid particles among others. To determine whether the modulation of ethanol sensitivity by Clic may be related to co-regulated oxidation-reduction processes, we evaluated the effect of hyperoxia on ethanol sedation in Clic knockdown flies. Consistent with previous findings, Clic knockdown reduced acute ethanol sedation sensitivity in flies housed under nomoxia. However, this effect was reversed by exposure to hyperoxia, suggesting a common set of molecular-genetic mechanism may modulate each of these processes. This study suggests that Drosophila Clic has a major influence on regulation of oxidative stress signaling and that this function overlaps with the molecular mechanisms of acute ethanol sensitivity in the fly.

Dataset Information

Corazonin Neurons Contribute to Dimorphic Ethanol Sedation Sensitivity in Drosophila melanogaster.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets