Abedi_2026_Neurotoxicol_117_103583

BACKGROUND: Nanoplastics, particularly polystyrene nanoparticles, may induce neurotoxicity. This study aimed to investigate the effects of nanopolystyrene (NP) on oxidative stress markers, the Bdnf/TrkB/Creb signaling pathway, and non-coding RNAs (ncRNA) in the hippocampus and cortex of mice, as well as to evaluate the protective effects of phycocyanin (PC) and phycocyanin nanoemulsion (NE). METHODS: Mice were exposed to NP either alone or in combination with PC or NE. Behavioral performance was assessed using the open field and novel object recognition tests. In addition, acetylcholinesterase (AChE) activity, antioxidant enzyme activities, the expression of genes associated with the antioxidant defense system, neurotrophic genes including Bdnf, Creb, and TrkB, as well as ncRNA including miR-132, Malat1, Neat1, H19, and Bdnf-as were evaluated in hippocampal and cortical tissues. RESULTS: Exposure to NP increased oxidative stress, reduced antioxidant enzyme activities, and downregulated the expression of antioxidant-related genes in both brain regions. Moreover, Bdnf, Creb, TrkB, and miR-132 expression levels were significantly decreased, while the long ncRNAs Malat1, Neat1, H19, and Bdnf-as were markedly upregulated. Decreased AChE activity and behavioral impairments were also observed. The hippocampus exhibited greater sensitivity to these alterations compared to the cortex. Treatment with phycocyanin ameliorated the molecular, oxidative, and behavioral alterations, while NE demonstrated stronger protective effects than the crude form. CONCLUSION: NP was associated with oxidative stress, behavioral impairments, altered expression of genes related to the Bdnf/TrkB/Creb signaling pathway, and dysregulated ncRNA expression. Phycocyanin, particularly in nanoemulsion form, attenuated these adverse changes, suggesting its potential as a neuroprotective agent against nanoplastic-induced brain alterations.