Planarians as an alternative in vivo model to study micro- and nanoparticle-induced neurodevelopmental toxicity

Abstract

Micro- and nanoparticles are present in our daily lives and form a potential threat to our health. Several of these particles have been shown to induce neurotoxicity, though the underlying mechanisms remain elusive. Understanding how particle characteristics and their uptake profiles influence toxicological responses is crucial for proper risk assessment. We studied this relationship in planarians, given their unique ability to regenerate a fully functional central nervous system. All studied particles induced neurodevelopmental toxicity, although their specific effects depend on particle characteristics and uptake profiles. Polystyrene particles of different sizes were taken up in the epidermis and intestine, and were found close to neuronal structures. The larger sizes (1 + 2 µm) resulted in a delay in anterior commissure formation, while the smaller particles (50 + 200 nm) affected the formation of the eyes and dopaminergic neurons. Silver and titaniumdioxide nanoparticles induced behavioral changes and a delayed formation of respectively the cephalic ganglia and anterior commissure, linked to altered stem cell dynamics. Currently, we focus on gaining in-depth mechanistic insights to identify adverse outcome pathways related to particle-induced neurotoxicity, providing new perspectives for risk assessment.