Copper and PFOS Co-Exposure Induces Synergistic Neurotoxicity via ROS-Mediated Mitophagy in C. elegans

Area of Science:

• Environmental toxicology
• Neuroscience
• Cell biology

Background:

• Copper (Cu) and perfluorooctanesulfonic acid (PFOS) are common pollutants with known individual neurotoxic effects.
• The combined toxicity and mechanisms of Cu and PFOS co-exposure are not well understood.
• Assessing combined environmental health risks is hindered by unclear interactive toxicity mechanisms.

Purpose of the Study:

• To investigate the synergistic neurotoxicity of co-exposed Cu and PFOS in the C. elegans model.
• To elucidate the underlying mechanisms of combined Cu and PFOS neurotoxicity.
• To evaluate the potential of antioxidant intervention against synergistic neurotoxicity.

Main Methods:

• Utilized the C. elegans model for co-exposure studies with environmentally relevant concentrations of Cu and PFOS.
• Assessed neurotoxicity endpoints including neuronal loss (dopaminergic and glutamatergic), locomotor deficits, reactive oxygen species (ROS) levels, and mitochondrial membrane potential.
• Examined mitochondrial ultrastructure, autophagosome accumulation, and the mitophagy pathway.
• Investigated the effects of N-acetylcysteine (NAC) as an antioxidant intervention.

Main Results:

• Co-exposure to Cu and PFOS induced synergistic neurotoxicity, exceeding the effects of individual exposures.
• Observed significant loss of dopaminergic and glutamatergic neurons, impaired locomotion, increased ROS, and reduced mitochondrial function.
• Found evidence of mitochondrial damage, autophagosome accumulation, and aberrant activation of ROS-mediated mitophagy.
• N-acetylcysteine (NAC) treatment effectively ameliorated the neurotoxic effects caused by co-exposure.

Conclusions:

• Cu and PFOS co-exposure exerts synergistic neurotoxicity through an oxidative stress-driven mitophagy pathway.
• Impaired mitochondrial quality control via excessive ROS-mediated mitophagy is a key mechanism.
• Oxidative stress is the central driver of synergistic neurotoxicity.
• Findings provide critical evidence for refining environmental risk assessments of combined Cu and PFOS pollution.