ORIGINAL RESEARCH article
Front. Toxicol.
Sec. Neurotoxicology
Volume 7 - 2025 | doi: 10.3389/ftox.2025.1636431
Arsenic Toxicity in the Drosophila Brain at Single Cell Resolution
Provisionally accepted
Anurag Chaturvedi
Vijay Shankar
Bibhu Simkhada
Rachel LymanPatrick FreymuthElisa HowanskyKatelynne Collins
Trudy Mackay*
Robert Anholt*- Clemson University, Clemson, United States
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Arsenic is an ubiquitous environmental toxicant with harmful physiological effects, including neurotoxicity. Modulation of arsenic-induced gene expression in the brain cannot be readily studied in human subjects. However, Drosophila allows quantification of transcriptional responses to neurotoxins at single cell resolution across the entire brain in a single analysis. We exposed Drosophila melanogaster to a chronic dose of NaAsO₂ that does not cause rapid lethality and measured survival and negative geotaxis as a proxy of sensorimotor integration. Females survive longer than males but show earlier physiological impairment in climbing ability. Single-nuclei RNA sequencing showed widespread sex-antagonistic transcriptional responses with modulation of gene expression in females biased toward neuronal cell populations and in males toward glial cells. However, differentially expressed genes implicate similar biological pathways. Evolutionary conservation of fundamental processes of the nervous system enabled us to translate arsenic-induced changes in transcript abundances from the Drosophila model to orthologous human neurogenetic networks.
Keywords: Neurotoxicity, Single Cell RNA sequencing, Behavioral genetics, sexual dimorphism, genetic networks
Received: 27 May 2025; Accepted: 25 Jun 2025.
Copyright: © 2025 Chaturvedi, Shankar, Simkhada, Lyman, Freymuth, Howansky, Collins, Mackay and Anholt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Trudy Mackay, Clemson University, Clemson, United States
Robert Anholt, Clemson University, Clemson, United States
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