76 Neurotoxic impact of atmospheric PM₁₀ from Catalonia: an <i>in vitro</i> study

Abstract Air pollution is a significant environmental risk to human health, causing around 4.2 million premature deaths annually due to cardiovascular, respiratory, and cancer-related conditions. Despite this, few studies have explored the neurotoxic effects of atmospheric pollutants, even though fine particles (PM₂.₅ and PM₁₀) can reach the brain through the bloodstream or olfactory bulb, leading to neuronal damage, oxidative stress, and neurodegenerative diseases such as Alzheimer’s and Parkinson’s. This study investigates the neurotoxic effects induced by atmospheric pollutants extracted from PM₁₀ filters collected at various air quality stations in Catalonia, including the rural background location Bellver and suburban locations Manlleu and Mollet del Vallès. Neurotoxicity was assessed using SH-SY5Y neuroblastoma cells to evaluate cell viability, reactive oxygen species (ROS) production, xenobiotic response (XRE), antioxidant response (ARE), and p53 pathway activation, as well as acetylcholinesterase (AChE) inhibition. Neurocortical brain organoids were used for lipidomic profiling to investigate the involvement of lipids in neurotoxic mechanisms. The chemical composition of filters, analysed via gas chromatography–mass spectrometry (GC–MS), quantified around 30 organic compounds, including biomarkers of biomass burning (levoglucosan, mannosan) and polycyclic aromatic hydrocarbons (PAHs). Multivariate analysis using Principal Component Analysis (PCA) and Multivariate Curve Resolution–Alternating Least Squares (MCR–ALS) integrated chemical and biological data, revealing seasonal patterns: winter samples showed greater oxidative stress, gene activation, and cytotoxicity, while warm-season samples exhibited milder oxidative and cholinergic responses. These findings provide insights into the biochemical mechanisms linking air pollution and neurotoxicity, highlighting the importance of integrated chemical–biological and multivariate approaches to assess the neurological risks of air pollution.