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The Impairing Effect of Oral Aluminum Oxide Nanoparticle on Novel Object Recognition Memory Coincides with Akt/GSK-3β Signaling Deregulation in Mice Hippocampus

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Abstract

The rise in annual production and applications of aluminum nanoparticles leads to elevation of the environmental and occupational exposures to this substance and might raise potential risk to the human health. Aluminum toxicity was suggested to have a role in the pathogenesis of Alzheimer’s disease. Considering the physicochemical properties of aluminum nanoparticle, such as its size, high reactivity, and high specific surface area, there is a concern about the impact of these nanoparticles on brain function. This study was designed to evaluate the effect of a 5-day oral gavage of aluminum oxide nanoparticle (ALNP) on memory and Akt/GSK-3β pathway as well as cleaved caspase-3 signaling in the hippocampus. Adult male NMRI mice were treated with ALNP in doses 5 and 10 mg/kg/oral gavage for 5 days. The novel object recognition (NOR) test session was performed on day 5. Following the behavioral assessments, the hippocampi were assessed for Akt/GSK-3β signaling using western blot technique. The results showed that ALNP oral gavage in doses 5 and 10 mg/kg impairs NOR memory in mice. Furthermore, it decreased the ratio of active to total level of Akt in the hippocampus while increased GSK-3β level in the hippocampus. The memory impairing effect of ALNP coincided with a dose-dependent increase in cleaved caspase-3. This study showed the deregulation of Akt/GSK-3β signaling and apoptosis in the hippocampus following oral aluminum oxide nanoparticle (ALNP) exposure.

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Funding

This work was supported by a grant (no. 20755) from Shiraz University of Medical Sciences, Shiraz, Iran.

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Conceptualization—Zahra Esmaili, Maryam Moosavi; methodology—Zahra Esmaili, Maryam Moosavi, Majid Reza Farokhi; formal analysis and investigation—Zahra Esmaili, Maryam Moosavi, Roksana Soukhaklari, Safura Absalan; writing (original draft preparation)—Maryam Moosavi; writing (review and editing)—Majid Reza Farokhi, Zahra Esmaili, Roksana Soukhaklari, Safura Absalan; funding acquisition—Maryam Moosavi; resources—Majid Reza Farokhi; supervision—Maryam Moosavi. All authors read and approved the manuscript.

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Correspondence to Maryam Moosavi.

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The protocols were approved by the Animals Experiment Ethics Committee of Shiraz University of Medical University, Shiraz, Iran (license # IR.SUMS.REC.1399.598). The present article does not contain any experiment on human subjects.

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Esmaili, Z., Soukhaklari, R., Farokhi, M.R. et al. The Impairing Effect of Oral Aluminum Oxide Nanoparticle on Novel Object Recognition Memory Coincides with Akt/GSK-3β Signaling Deregulation in Mice Hippocampus. BioNanoSci. 11, 1119–1126 (2021). https://doi.org/10.1007/s12668-021-00908-4

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