Synergistic neurological threat from Сu and wood smoke particulate matter

Trace metal Cu and carbonaceous airborn particulate matter (PM) are dangerous neuropollutants. Here, the ability of Cu²⁺ to modulate the neurotoxicity caused by water-suspended wood smoke PM preparations (SPs) and vice versa was examined using presynaptic rat cortex nerve terminals. Interaction of Cu²⁺ and SPs, changes of particle size and surface properties were shown in the presence of Cu²⁺ using microscopy, DLS, and IR spectroscopy. In nerve terminals, Cu²⁺ and SPs per se elevated the ambient levels of excitatory and inhibitory neurotransmitters L-[¹⁴C]glutamate and [³H]GABA, respectively. During combined application, Cu²⁺ significantly enhanced a SPs-induced increase in the ambient levels of both neurotransmitters, thereby demonstrating a cumulative synergistic effect and significant interference in the neurotoxic threat associated with Cu²⁺and SPs. In fluorimetric measurements, Cu²⁺ and SPs also demonstrated cumulative synergistic effects on the membrane potential, mitochondrial potential, synaptic vesicle acidification and ROS generation. Therefore, synergistic effects of Cu²⁺ and SPs on the most crucial presynaptic characteristics and neurohazard of multiple pollutants through excitatory/inhibitory imbalance, disruption of the membrane and mitochondrial potential, vesicle acidification and ROS generation were revealed. Increased expansion and burden of neuropathology may result from underestimation of synergistic interference of the neurotoxic effects of Cu²⁺ and carbonaceous smoke PM.