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Neurotoxic synergy of copper and PVC microplastics triggers apoptosis via the BDNF/miR132/FOXO3a pathway for the first time in fish brain
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This study found that copper and PVC microplastics together cause far worse brain damage in fish than either pollutant alone, triggering nerve cell death through a specific molecular pathway. While conducted in fish, the findings raise concerns about how combined exposure to microplastics and heavy metals in contaminated water could amplify neurotoxic effects in other species, including humans.
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.
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Researchers exposed zebrafish to copper and PVC microplastics at environmentally relevant concentrations and found for the first time that the combination triggers CuPANoptosis — a novel cell death pathway integrating cuproptosis and PANoptosis — with PVC increasing gut copper load by 1.6–1.9-fold.
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Researchers investigated the chronic effects of microplastics and copper, alone and combined, on zebrafish brains over 30 days. The study found that both contaminants induced apoptosis, altered neurotransmitter pathways, and caused behavioral changes including increased anxiety, with combined exposure producing more severe effects than either pollutant alone.
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Researchers studied the combined effects of PVC microplastics and copper on a marine fish species and found that the two pollutants together caused significantly more harm than either one alone. The microplastics accelerated copper buildup in the fish's liver, leading to greater oxidative damage and growth problems. This is relevant to human health because fish that accumulate both microplastics and heavy metals may pass those contaminants to people through the food chain.
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When marine medaka fish were exposed to both nanoplastics and the toxic chemical triphenyltin together, they showed much worse nerve and behavioral damage than from either pollutant alone. The combined exposure significantly reduced the fish's swimming ability and disrupted neural gene expression, with smaller nanoplastics causing more severe effects than larger microplastics. This highlights that real-world conditions, where microplastics coexist with other pollutants, may produce amplified toxic effects on the nervous system.
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Researchers found that PVC microplastics loaded with copper caused severe liver damage in fish through a process called endoplasmic reticulum stress, which triggers cell death. The combined exposure to microplastics and copper was more harmful than either pollutant alone. This study demonstrates how microplastics can act as carriers for toxic metals, amplifying their harmful effects on organ health.
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