A study on cognitive impairment of mice exposed to nano-alumina particles by nasal drip.

Background: As an emerging nanomaterial, nano-alumina is widely used in chemical engineering, food and medicine due to its special physical and chemical properties, and its potential health hazards have attracted attention.

Objective: Aim of this study is to understanding the effect and possible mechanism of nano-alumina on cognitive function in mice.

Methods: Male healthy ICR mice were randomly assigned and given nasal drops of saline, nano-alumina (different doses) and micro-alumina for 30 days, respectively. Morris water maze test, step down test and open field test were used to detect learning and memory ability. Blood brain permeability was observed by immunofluorescence staining and lanthanum nitrate tracing, histopathological abnormalities in mice hippocampus was observed by thionine staining, the final determination of oxidative stress level in brain tissue was measured by using oxidative stress index detection kit and the level of LC3-Ⅱ and Caspase-3, 8, 9 proteins were detected by western blot.

Results: In the cerebral cortex of mice exposed to nano-alumina particles, lanthanum nitrate particles adhered to vascular endothelial cells, and the expression of ZO-1 and Occuldin decreased and morphology was disordered; most neurons in hippocampus CA3 region showed balloon-like swelling and degeneration, nucleoli disappeared and apical dendrites broke; mice exposed to nano-alumina, the escape latency in Morris water maze increased compared with the control group(P < 0.05),and the residence time in the original platform quadrant shortened significantly(P < 0.05);the platform latency was significantly shortened and the number of errors increased in the step down test compared with the control group; the residence time in the center of mice the nano-alumina treated was significantly increased in open field test (P < 0.05).

Conclusion: The nano-alumina particles could be transported into the central nervous system via blood-brain barrier and olfactory bulb, impair learning and memory function in mice, which is more serious than the micro-alumina particles. The apoptosis of mice neurons caused by nano-alumina particles maybe due to the mixed neurotoxic effect of oxidative stress and the elemental toxicity of aluminum itself.