Polystyrene Micro- and Nanoplastic Exposure Triggers an Activation and Stress Response in Human Astrocytes

Recent evidence indicates the presence of micro- and nanoplastics in the human brain, with higher accumulation observed in patients with dementia. However, their mechanistic effects on the human brain at the cellular level remain underexplored. Astrocytes play a crucial role in repairing neurons following injury. The dysfunction of these cells can lead to chronic inflammation, a hallmark of neurodegenerative diseases. Here, we investigated the cytotoxic responses of primary human astrocytes exposed to polystyrene particles of two representative sizes, 25 nm and 1 µm, at concentrations of 1 µg/mL and 5 µg/mL for 48 h. Flow cytometry and confocal microscopy revealed the accumulation of particles of both sizes within the cytoplasm. Functional assays revealed reduced cell viability and elevated lactate dehydrogenase release, indicating cytotoxic effects following microplastic exposure. Gene expression analysis showed significant upregulation of MAPK14 and SOD2, indicating oxidative stress activation, and increased expression of pro-inflammatory mediators IL-6, TNF-α, and NF-κB1. In parallel, GLUT1 transcripts and GLUT1-positive cell populations were markedly reduced, suggesting impaired glucose metabolism. Collectively, these findings demonstrate that microplastics disrupt astrocytic homeostasis by inducing oxidative, inflammatory, and metabolic disturbances, leading to a reactive yet metabolically compromised phenotype. This study demonstrates the cellular damage caused by microplastics in astrocytes, which may contribute to a cellular mechanism linking environmental pollutant exposure to adverse effects on human health.