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 25 nm. The synthesised nCeO2 were then administered as part of the diet to transgenic Drosophila for one month, at 0.1 and 1 mM 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 1 mM 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 1 mM 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.
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Acknowledgements
Dr Sahabudeen acknowledges the Department of Science and Technology (DST) −Science and Engineering Research Board (FILE NO. ECR/2016/000490) for providing financial assistance. The authors acknowledge HRTEM, XRD and Raman facilities at SRM Institute of Science and Technology set up with support from MNRE (Project No. 31/03/2014-15/PVSE-R&D), Government of India. The authors acknowledge the SRM-DBT Platform for Advanced Life Sciences for providing the facility for performing Real-Time PCR experiments. The authors also thank Mr. V.P. Narayanan Nampoothiri for technical assistance.
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Sundararajan, V., Venkatasubbu, G.D. & Sheik Mohideen, S. Investigation of therapeutic potential of cerium oxide nanoparticles in Alzheimer’s disease using transgenic Drosophila. 3 Biotech 11, 159 (2021). https://doi.org/10.1007/s13205-021-02706-x
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DOI: https://doi.org/10.1007/s13205-021-02706-x