A stereological study reveals nanoscale-alumina induces cognitive dysfunction in mice related to hippocampal structural changes

Aluminum (Al) is known to induce neurotoxicity in both humans and rodents. Recent evidence has indicated that the toxicity of Al Oxide (Al2O3) nanoparticles (Al-NP), one of the most abundantly used engineered nanoparticles, is far greater than that of Al itself. To date, however, no information is available regarding the effect of Al-NP on the stereological parameters of hippocampus. In particular, no stereological studies have evaluated the effect of Al-NP on hippocampal CA1, dentate gyrus volume, and number of pyramidal and granular cells. Thus, the present study aimed to take a multidimensional approach to assess the concomitant cognitive, stereological, and apoptotic changes induced by a five-day Al-NP ingestion (10 mg/kg/day) in mice. The results demonstrated that the five-day Al-NP ingestion elicited a reduced preference to explore a novel object in the novel object recognition test (a hippocampal-dependent task). Perhaps contributing to this memory deficit, Al-NP induced additional alterations in the hippocampus of male NMRI mice in terms of (1) hippocampal volume (decreased the volume of the whole hippocampus, CA1, and dentate gyrus regions), (2) cell number (decreased the number of CA1 pyramidal neurons and dentate gyrus granular cells), and (3) increased cleaved caspase-3 in the whole hippocampus. These results provided new mechanistic insight to understand the impairing effect of AL-NP on the hippocampal function and structure.