Cationic nanoplastic causes mitochondrial dysfunction in neural progenitor cells and impairs hippocampal neurogenesis.

ABSTRACT

Nanoplastics (NPs) exposure to humans can occur through various routes, including the food chain, drinking water, skin contact, and respiration. NPs are plastics with a diameter of less than 100 nm and have the potential to accumulate in tissues, leading to toxic effects. This study aimed to investigate the neurotoxicity of polystyrene NPs on neural progenitor cells (NPCs) and hippocampal neurogenesis in a rodent model. Toxicity screening of polystyrene NPs based on their charge revealed that cationic amine-modified polystyrene (PS-NH3+) exhibited cytotoxicity, while anionic carboxylate-modified polystyrene (PS-COO-) and neutral NPs (PS) did not. NPCs treated with PS-NH3+ showed a significant reduction in growth rate due to G1 cell cycle arrest. PS-NH3+ increased the expression of cell cycle arrest markers p21 and p27, while decreasing cyclin D expression in NPCs. Interestingly, PS-NH3+ accumulated in mitochondria, leading to mitochondrial dysfunction and energy depletion, which caused G1 cell cycle arrest. Prolonged exposure to PS-NH3+ in C17.2 NPCs increased the expression of p16 and senescence-associated secretory phenotype factors, indicating cellular senescence. In vivo studies using C57BL/6 mice demonstrated impaired hippocampal neurogenesis and memory retention after 10 days of PS-NH3+ administration. This study suggests that NPs could deplete neural stem cell pools in the brain by mitochondrial dysfunction, thereby adversely affecting hippocampal neurogenesis and neurocognitive functions.