Neurotoxicity of copper and copper oxide nanoparticles

Overexposure to copper (Cu) nanoparticles (NPs), especially metallic CuNPs and CuONPs, is associated with adverse health effects, with higher susceptibility of the brain cells to their toxic effects. However, the particular mechanisms associated with their neurotoxicity are yet unclear. Therefore, the objective of the present review was to discuss the effects of CuNPs and CuONPs, and the molecular mechanisms underlying their neurotoxicity. In vivo studies with laboratory rodents, fishes, and invertebrate species have shown that both acute and chronic exposure to CuNPs/CuONPs induce neurotoxic effects, resulting in morphological brain alterations and behavioral defects. These findings are in agreement with results from in vitro studies, showing cytotoxic effects of CuNPs and CuONPs in neuronal or neuron-like (primary cultured neurons, SH-SY5Y, N2a, HT22), primary cultured astrocytes, microglial (BV2) cell cultures. Further, it has been demonstrated that both CuNPs and CuONPs induce neurotoxic effects through oxidative stress and apoptosis, impaired neurotransmitter metabolism, neuroinflammation, increased formation and toxicity of Aβ and α-synuclein, and aberrant expression of neurogenesis-related genes. Concomitantly, CuONPs also disrupt mitochondrial dynamics, damage the blood-brain barrier (BBB) and cause cell cycle arrest in neurons. The neurotoxic effects of CuNPs and CuONPs are determined by particle size, shape, solubility, and surface characteristics.