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TRPV1-Independent and Sex-Specific Capsaicin Signatures in Drosophila

ABSTRACT: In mammals, capsaicin activates the transient receptor potential vanilloid 1 (TRPV1) channel to induce pungency, but its effects in species lacking TRPV1 remain unclear. In Drosophila melanogaster, which has no TRPV1 ortholog, capsaicin triggers proboscis reflexes, drives attraction, and shapes feeding and locomotion in a sex- specific manner. Females exhibit delayed habituation and increased sleep fragmentation, whereas both sexes reduce evening locomotion. Single-nucleus RNA sequencing (snRNA-seq) revealed broader transcriptional responses in females, including modulation of peptidergic neurons and circadian-linked glial clusters. Cell–cell communication analyses identified a female-biased TGF-β and AstA signaling axis in learning and memory centers, contrasting with male-enriched WNT, NPF, and Dh31 pathways. These results uncover TRPV1-independent mechanisms through which capsaicin influences neural circuits, highlighting sex-specific strategies for integrating sensory cues and providing a framework to explore the ecological and evolutionary significance of capsaicin sensitivity beyond nociception.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE305959 | GEO | 2025/09/26

REPOSITORIES: GEO

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Project description:The number and type of synthetic chemicals that are being produced worldwide continues to increase significantly. While these industrial chemicals provide numerous benefits, there is no doubt that some have potential to damage the environment and health. Toxicity must be evaluated and use must be carefully controlled and monitored in order to minimize potential damage. DNA microarray technology has become an important new technique in toxicology. We are using the yeast Saccharomyces cerevisiae as a model organism for toxicological study because it is a simple, fast-growing eukaryote that has been thoroughly characterized. In order to evaluate toxicity by newly synthesized or mixture chemicals, toxicity-induced gene expression alteration profiles by known chemicals should be collected. In our study, cells need to be exposed with same experimental cellular condition, semi lethal (IC50), respectively. In the case of capsaicin (CAS; 404-86-4), the exposure dose was decided as 250 ppm by growth curve with continuously diluted exposure. Capsaicin, active component of chilli peppers, is an irritant for mammals, including humans, and produces a sensation of burning in any tissue with which it comes into contact. // Studies on the antimicrobial mechanisms of capsaicin using yeast DNA microarray: Capsaicin is a pungent element in a variety of red peppers that are widely used as food additives and considered to be an antimicrobial factor. For our tests, we used yeast DNA micro-array methods to understand the mechanisms of inhibitory effects of capsaicin. The capsaicin treatment significantly induced 39 genes from approximately 6,000 genes. These induced genes were classified as multi-drug resistance transporter genes, membrane biosynthesis genes, genes encoding stress proteins, and uncharacterized genes. The growth abilities of the strains with the deletion of the induced genes suggest that capsaicin is pumped out of the yeast cells by the PDR5 transporter. Keywords: stress response

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TRPV1-Independent and Sex-Specific Capsaicin Signatures in Drosophila

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