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Involvement of Mitophagy in Aluminum Oxide Nanoparticle–Induced Impairment of Learning and Memory in Mice

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Abstract

Aluminum oxide nanoparticles (nano-aluminum) have been known to be widespread in the environment for decades. Exposure to nano-aluminum may impair learning and memory, but the potential mechanism has not yet been elucidated. In neurons, efficient clearance of damaged mitochondria through mitophagy plays an important role in mitochondrial energy supply, neuronal survival, and health. However, abnormal mitophagy induces accumulation of damaged mitochondria, which induces cellular dysfunction, contributing to the impairment of learning and memory. It is currently unclear whether nano-aluminum interferes with the function of nerve cells through mitophagy, leading to learning and memory disorders. Institute of Cancer Research (ICR) female mice were randomly divided into four groups, and treated with normal saline (control) and 50 nm nano-aluminum at concentrations of 25, 50, and 75 mg/kg for 30 days. Our results showed that exposure to nano-aluminum impaired the spatial learning and memory of mice. Superoxide dismutase levels decreased, whereas the levels of malondialdehyde increased. Moreover, there were significant pathological changes in the ultra-structure and function of mitochondria. Finally, expression of autophagy-related proteins LC3-II and Beclin-1 was upregulated and p62 expression decreased, but the expression of apoptotic and necrosis-related proteins had no significant difference among groups. Our results suggest that learning and memory impairment induced by nano-aluminum could be related to mitophagy.

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Funding

This research was financially supported by the National Natural Science Foundation of China (No. 81430078, 30972456), and Natural Science Foundation of Shanxi Province (No. 201901D111203).

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Correspondence to Qinli Zhang.

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The authors declare that they have no conflict of interest.

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Co-first authors are Tao Huang and Weiwei Guo

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Huang, T., Guo, W., Wang, Y. et al. Involvement of Mitophagy in Aluminum Oxide Nanoparticle–Induced Impairment of Learning and Memory in Mice. Neurotox Res 39, 378–391 (2021). https://doi.org/10.1007/s12640-020-00283-0

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  • DOI: https://doi.org/10.1007/s12640-020-00283-0

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