Bakhasha_2025_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__110265

Copper (Cu) and polyvinyl chloride microplastics (PVC-MPs), each known for their toxic effects, combine to create a hazardous synergy, posing a dual threat to aquatic ecosystems. Our study investigates the chronic (60-day) neurotoxic impacts of environmentally relevant concentrations of Cu (0.85 mg/L) and PVC-MPs (0.5 mg/L), both individually and in combination, in freshwater food-fish Channa punctatus. The neurotoxic effects were evaluated through reactive oxygen species (ROS) generation; oxidative damage to lipids, proteins, and nucleic acids; disruption of neurotransmitters; neuro-architectural damage, and neuronal cell death. For the first time, we identified neural apoptosis in fish via the BDNF/miR132/FOXO3a axis upon exposure to Cu, PVC-MPs, and their mixture. Cu accumulation peaked in brains treated with Cu-PVC-MPs combination. Higher ROS levels were seen in the exposed brain tissue, along with signs of oxidative damage, such as increased lipid peroxidation (LPO), protein carbonyls (PC), and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Increased monoamine oxidase (MAO) activity led to dopamine and serotonin depletion, while cholinergic dysfunction was marked by reduced choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and acetylcholine (ACh). Additionally, severe neuro-architectural damage was observed. Molecular alterations were amplified in brains exposed to the copper-PVC-MPs mixture. Transcriptional analyses revealed downregulation of bdnf, miR132 and bcl2, with concurrent upregulation of foxo3a, bim, bax, apaf1, cas9, and cas3, further validated apoptosis. Principal Component Analysis (PCA) and Pearson Correlation analyses were also performed to validate these findings. Our results underscore the growing environmental threat posed by combined copper and MPs pollution, with PVC acting as a vehicle for increased toxicity in aquatic life.