Chronic Al2O3-nanoparticle exposure causes neurotoxic effects on locomotion behaviors by inducing severe ROS production and disruption of ROS defense mechanisms in nematode Caenorhabditis elegans

► Chronic exposure to Al2O3-NP caused adverse effects on locomotion behaviors. ► Chronic Al2O3-NP exposure induced ROS production and ROS defense mechanism disruption. ► sod-2 and sod-3 mutants were susceptible to Al2O3-NP-induced neurotoxicity inhibition. To date, knowledge on mechanisms regarding the chronic nanotoxicity is still largely minimal. In the present study, the effect of chronic (10-day) Al2O3-nanoparticles (NPs) toxicity on locomotion behavior was investigated in the nematode Caenorhabditis elegans. Exposure to 0.01–23.1mg/L of Al2O3-NPs induced a decrease in locomotion behavior, a severe stress response, and a severe oxidative stress; however, these effects were only detected in nematodes exposed to 23.1mg/L of bulk Al2O3. Formation of significant oxidative stress in nematodes exposed to Al2O3-NPs was due to both the increase in ROS production and the suppression of ROS defense mechanisms. More pronounced increases in ROS, decreases in SOD activity, and decrease in expression of genes encoding Mn-SODs (sod-2 and sod-3) were detected in nematodes exposed to Al2O3-NPs compared with bulk Al2O3. Moreover, treatment with antioxidants or SOD-3 overexpression not only suppressed oxidative stress but also prevented adverse effects on locomotion behaviors from Al2O3-NPs exposure. Thus, chronic exposure to Al2O3-NPs may have adverse effects on locomotion behaviors by both induction of ROS production and disruption of ROS defense mechanisms. Furthermore, sod-2 and sod-3 mutants were more susceptible than the wild-type to chronic Al2O3-NPs-induced neurotoxicity inhibition.