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

Although <i>Caenorhabditis elegans</i> 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 <i>C. elegans</i>. Proteomics of 4-day-old <i>C. elegans</i> 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 <i>C. elegans</i> 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.