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Sub-Chronic Aluminum Exposure in Rats’ Learning-Memory Capability and Hippocampal Histone H4 Acetylation Modification: Effects and Mechanisms

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Abstract

Aluminum has been found to be closely related to the pathogenesis of neurodegenerative diseases and damage learning and memory functions. Many changes in epigenetics may be one of the mechanisms of aluminum neurotoxicity. The purpose of this study is to further investigate the mechanism of action of sub-chronic aluminum exposure on learning memory and histone H4 acetylation modification in Wistar rats, and the correlation between learning memory impairment and histone H4 acetylation in aluminum-exposed rats. Rats in each dose group were given 0.0 g/L, 2.0 g/L, 4.0 g/L, and 8.0 g/L of AlCl3 distilled water daily for 12 weeks. The learning and memory ability of rats was measured by the Morris water maze test; the neuronal morphology of rat hippocampus was observed by Nissl staining and transmission electron microscope; real-time PCR, and Western blot were used to detect mRNA expression and protein content in hippocampus of rats. The results suggest that aluminum may affect the gene and protein expression of HAT1 and HDAC2, and then affect histone H4 and the acetylation of H4K12 (acH4K12), which may lead to learning and memory dysfunction in rats.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors sincerely appreciate the support of everyone. Thank the correspondent for guiding the manuscript.

Funding

This research was supported by the National Natural Science Foundation of China (81673226); by the Initiated Research Foundation for the Doctoral Program of Science and Technology Department of Liaoning Province, China (201601226); by the Natural Science Foundation of Education Department of Liaoning Province, China (L2015544, LJKZ1146); by the Natural Science Foundation for Innovation and Entrepreneurship Training Program of Education Department of Liaoning Province, China (201710164000038); by the Natural Science Foundation of Science and Technology Department of Shenyang City, China (17–231-1–44); by the Natural Science Foundation of Shenyang Medical College, China (20153043); by the Natural Science Foundation for graduate students of Shenyang Medical College, China (Y20180512); and by the Natural Science Foundation for undergraduate students of Shenyang Medical College, China (20179028).

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Author notes

  1. Jie Gao, Shiming Zhang and Bing Li contributed equally to the presented study.

Authors and Affiliations

  1. Department of Maternal, Child and Adolescent Health, School of Public Health, Shenyang Medical College, Shenyang, Liaoning, 110034, People’s Republic of China

    Jie Gao, Shiming Zhang, Wei Liu & Lifeng Zhang

  2. Department of Dermatology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People’s Republic of China

    Bing Li

  3. Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, People’s Republic of China

    Ziyi Wang

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  1. Jie Gao
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Contributions

Jie Gao: conceptualization, methodology, software, data curation, writing—original draft, writing–review and editing. Shiming Zhang: methodology, data curation, writing—original draft. Bing Li: methodology, data curation, writing—original draft. Ziyi Wang: methodology, data curation, writing—original draft. Wei Liu: methodology, data curation, writing—original draft. Lifeng Zhang: conceptualization, methodology, writing—review and editing, supervision.

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Correspondence to Lifeng Zhang.

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Gao, J., Zhang, S., Li, B. et al. Sub-Chronic Aluminum Exposure in Rats’ Learning-Memory Capability and Hippocampal Histone H4 Acetylation Modification: Effects and Mechanisms. Biol Trace Elem Res 201, 5309–5320 (2023). https://doi.org/10.1007/s12011-023-03602-6

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