Quercetin mitigates aluminum nanoparticle-induced neurotoxicity: a stereological and molecular study on memory, hippocampal integrity, and MAPK signaling
DOI:
https://doi.org/10.17179/excli2025-8315Keywords:
Aluminum nanoparticles, quercetin, hippocampus, Alzheimer’s disease, MAPK signaling, stereology, neuroprotectionAbstract
Emerging evidence suggests a strong association between aluminum (Al) exposure and the development of Alzheimer’s disease (AD). Due to their nanoscale size and increased surface area, Al nanoparticles (ALNP) exhibit greater neurotoxicity than bulk Al, raising concerns about their role in neurodegenerative disorders. While quercetin has been recognized for its neuroprotective effects, its ability to counteract ALNP-induced hippocampal neurodegeneration and dysregulated MAPK signaling remains largely unexplored. This study investigated the potential of quercetin to ameliorate ALNP-induced memory deficits, alterations in hippocampal stereological parameters, and disruptions in caspase-3 and MAPK signaling in male Swiss mice. Mice (SWR/J, aged 8–10 weeks) received ALNP (10 mg/kg, intraperitoneally for 10 days) with or without quercetin at doses of 1, 10, or 100 mg/kg (orally). Memory performance was assessed using the elevated plus maze (EPM), novel object recognition (NOR), and Y-maze tasks, followed by stereological and western blot analyses of the hippocampus. Our findings revealed that quercetin (100 mg/kg) significantly preserved hippocampal volume and neuronal integrity in the dentate gyrus (DG) and Cornu Ammonis 1 (CA1)—key regions involved in memory processing and output signaling. Additionally, quercetin modulated MAPK signaling by enhancing ERK phosphorylation while suppressing ALNP-induced activation of p38 and cleaved caspase-3, suggesting a role in reducing neuroinflammation and apoptosis. This is the first study to demonstrate that quercetin can counteract the neurotoxic effects of ALNP, highlighting its potential as a therapeutic strategy against nanoparticle-induced neurodegeneration in an Alzheimer’s-like model.
Downloads
Published
How to Cite
License
Copyright (c) 2025 Zahra Esmaili, Mohammad Shabani, Fatemeh Karimi, Moazamehosadat Razavinasab, Meysam Ahmadi-Zeidabadi, Majid Reza Farokhi, Maryam Moosavi
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish in this journal agree to the following terms:
- The authors keep the copyright and grant the journal the right of first publication under the terms of the Creative Commons Attribution license, CC BY 4.0. This licencse permits unrestricted use, distribution and reproduction in any medium, provided that the original work is properly cited.
- The use of general descriptive names, trade names, trademarks, and so forth in this publication, even if not specifically identified, does not imply that these names are not protected by the relevant laws and regulations.
- Because the advice and information in this journal are believed to be true and accurate at the time of publication, neither the authors, the editors, nor the publisher accept any legal responsibility for any errors or omissions presented in the publication. The publisher makes no guarantee, express or implied, with respect to the material contained herein.
- The authors can enter into additional contracts for the non-exclusive distribution of the journal's published version by citing the initial publication in this journal (e.g. publishing in an institutional repository or in a book).
