# Arsenic toxicity in the Drosophila brain at single cell resolution

## TL;DR

The study uses fruit flies to explore how arsenic affects brain cells at a detailed level, revealing sex-specific responses and conserved effects in humans.

## Contribution

The study introduces a novel approach using Drosophila to analyze arsenic-induced transcriptional responses at single-cell resolution and translates findings to human neurogenetic networks.

## Key findings

- Females survive longer than males after arsenic exposure but show earlier sensorimotor impairment.
- Single-nuclei RNA sequencing reveals sex-antagonistic transcriptional responses with distinct cell-type biases.
- Arsenic-induced gene expression changes in Drosophila are translatable to human neurogenetic networks.

## Abstract

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.