# Loss of γ-aminobutyric acid D-Type Motor Neurons in Young Adult Caenorhabditis elegans Following Exposition with Silica Nanoparticles

## TL;DR

This study shows that exposure to silica nanoparticles causes specific nerve cell loss in young adult worms, mimicking age-related neurodegeneration.

## Contribution

A novel model for pollutant-induced neurodegeneration in C. elegans, revealing age-specific vulnerabilities and metabolic disruptions.

## Key findings

- Silica nanoparticles cause loss of GABAergic D-type motor neurons in young adult C. elegans.
- Proteomic analysis shows downregulation of key GABA metabolic enzymes like gdh-1 and got-1.2.
- A semi-automated behavioral arena quantifies locomotion deficits in exposed worms.

## Abstract

Although Caenorhabditis elegans is commonly used to assess the neurotoxicity of environmental pollutants, studies that explore the intricate biology of its nervous system, particularly those addressing long-term effects and aging in adult worms, are rare. These models offer significant advantages for understanding the full spectrum of neurobiological impacts. Here, we investigated the effects of silica nanomaterials on the γ-aminobutyric acid (GABA) neural system in young to middle-aged nematodes and found a unique degeneration pattern characterized by loss of anterior- and posteriormost GABAergic D-type motor neurons. Four-day-old nematodes were identified as a vulnerable age group, where the pollutant-accelerated neurodegeneration that is typically seen in old C. elegans. Proteomics of 4-day-old C. elegans revealed significant alterations of protein abundance, including the downregulation of proteins such as glutamate dehydrogenase (gdh-1) and glutamate oxaloacetate transaminase (got-1.2), which are essentially involved in GABA metabolic pathways. Consistent with these findings, we demonstrated locomotion deficits in C. elegans exposed to nanoscale silica by establishing a semi-automated behavioral arena. Our setup not only visualizes but also automatically quantifies vulnerabilities at the individual worm level. This novel neurodegeneration model now enables the simulation of real-world pollutant mixtures and environmental conditions, capturing the complexity of the exposome.