ORIGINAL ABSTRACT

The effects of nano- and microplastics (NMPs) on the mammalian central nervous system (CNS) remain insufficiently characterized. Here, rats were exposed by a single intraperitoneal administration to 0.5 or 1 μm polystyrene NMPs (NMP-PS, 10 mg/kg), alone or combined with glyphosate (GLY, 7.5 mg/kg). Seventy-two Sprague-Dawley rats were used in the research, which were randomly divided into twelve groups of six males and six females each. Locomotor behavior, acetylcholinesterase (AChE) activity, antioxidant capacity (expressed as Trolox equivalents), and lipid peroxidation (malondialdehyde levels) were assessed in the prefrontal cortex, striatum, and hippocampus of female and male rats 24 h post-exposure. Both NMP-PS sizes induced significant neurotoxic effects 24 h post-exposure, with 1 μm particles causing more pronounced effects. Females tended to show more pronounced alterations, and the hippocampus emerged as the most vulnerable region, showing the greatest changes in AChE activity and oxidative stress. Co-exposure to NMP-PS and GLY altered the effects of each toxicant alone, with interactions ranging from additive to potentiating or antagonistic, depending on the endpoint and brain region. The most striking changes occurred after 1 μm NMP-PS+GLY co-administration, especially in females, with clear potentiation of motor deficits, increased AChE inhibition, and reduced antioxidant capacity in the hippocampus. Antagonistic effects were also observed for malondialdehyde levels in some regions. Overall, these findings highlight the complexity of combined exposures and support the hypothesis that NMP-PS may adsorb and facilitate GLY transport to the brain, enhancing its neurotoxicity. This study underscores the importance of considering pollutant mixtures and sex-related susceptibility in neurotoxicological risk assessment.