Abstract

Plastic production continues to rise in 2025, despite environmental concerns and growing evidence pointing to its adverse impact on human health. Our knowledge of how micro- and nano-plastics affect brain health is, however, still in its infancy. To understand how neurons respond to stress caused by plastics, we exposed primary neurons to polystyrene nanoplastics (PS-NPs). We evaluated effects of the three different sizes of PS-NPs (50, 100, and 250 nm) at concentrations ranging from 0.05 μg/ml to 1 μg/ml. The exposure, relatively low in the tested concentrations and short in the exposure regimen (24 h), did not lead to impairments in neuronal metabolism. However, confocal imaging confirmed the uptake of 250 nm particles by neurons. Despite the lack of metabolic effects, the treatment contributed to neurite elongation in a size-specific manner: the effects were observed upon 50 nm PS-NPs treatment, but not when challenged by the 250 nm particles. Furthermore, subtle but statistically significant changes in the neuronal transcriptome were induced by the smaller, but not larger particles. Additionally, electrophysiological measurements of firing rate and spike amplitude at the time points of 2 and 24 h were not affected by the PS-NPs treatment. These findings highlight the importance of focusing further research specifically on nanoscale plastic particles in the context of brain health.