Investigation of therapeutic potential of cerium oxide nanoparticles in Alzheimer's disease using transgenic Drosophila.

Abstract

In the current study, the therapeutic potential of cerium oxide nanoparticles (nCeO2) was investigated in a human tau (htau) model of Alzheimer's disease (AD), using Drosophila melanogaster as an in vivo model. nCeO2 synthesised via the hydroxide-mediated approach were characterised using Fourier transform infrared (FTIR), transmission electron microscopy (TEM), X-ray diffraction (XRD) analyses and Raman spectroscopy. Characterisation studies confirmed the formation of pure cubic-structured nCeO2 and showed that the particles were spherically shaped, with an average size between 20 and 25nm. The synthesised nCeO2 were then administered as part of the diet to transgenic Drosophila for onemonth, at 0.1 and 1mM concentrations, and its effect on the biochemical levels of superoxide dismutase (SOD), acetylcholinesterase (AChE), and the climbing activity of flies were studied in a pan-neuronal model (elav; htau) of AD. Using an eye-specific model of htau expression (GMR; htau), the effect of nCeO2 on htau and autophagy-related (ATG) gene expression was also studied. Dietary administration of nCeO2 at a concentration of 1mM restored the activity of SOD similar to that of control, but both concentrations of nCeO2 failed to modulate the level of AChE, and did not elicit any significant improvements in the climbing activity of elav; htau flies. Moreover, nCeO2 at a concentration of 1mM significantly affected the climbing activity of elav; htau flies. nCeO2 also elicited a significant decrease in htau gene expression at both concentrations and increased the mRNA expression of key autophagy genes ATG1 and ATG18. The results therefore indicate that nCeO2 aids in replenishing the levels of SOD and tau clearance via the activation of autophagy.