Alumina nanoparticles induce learning and memory impairment in a particle size-dependent and time-dependent manner

The study investigates the influence of alumina nanoparticles (Al₂O₃ NPs) at varying sizes on the learning and memory of adult ICR mice over different exposure durations. The mice were administered saline or Al₂O₃ nanoparticles of 10μm, 50 nm, and 13 nm via nasal drip. Following administration, the Morris water maze test was conducted, along with assessments of inflammation, oxidative stress, hippocampal histopathology, and cell death-related proteins. Initially, after acute exposure, a trend emerged where learning and memory gradually declined as nanoparticle size decreased, with the most significant impact observed in the 13 nm Al₂O₃ group. Upon chronic exposure, there was a significant decline in learning and memory within the Al₂O₃ NPs groups compared to other groups, accompanied by neuronal loss, swelling, light staining, and disorganization. Concurrently, levels of TNF-α and IL-1β within 7 days, MDA after 7 days, and death-related proteins such as Cathepsin-B, c-caspase3, LC3-II, Beclin1, RIP, and Cathepsin-L showed a linear increase, while SOD and GSH-PX activity steadily decreased. Over time, learning capability decreased, correlating with a sharp reduction in TNF-α and SOD activity, a gradual increase in MDA, c-caspase3, and Beclin1 levels in the Al₂O₃ NPs group, as well as elevated Cathepsin-L, LC3-II, and RIP levels in the 13 nm Al₂O₃ group. Consequently, Al₂O₃ NPs significantly impaired learning and memory in a particle size-dependent manner through initial inflammation and oxidative stress after acute exposure, and time-dependent impairment via escalating oxidative stress and neuronal death.