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The Role of Acetylation and Methylation of Rat Hippocampal Histone H3 in the Mechanism of Aluminum-Induced Neurotoxicity

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Abstract

Aluminum is a known neurotoxin and a major environmental contributor to neurodegenerative diseases such as Alzheimer’s disease (AD). We uesd a subchronic aluminum chloride exposure model in offspring rats by continuously treating them with AlCl3 solution from the date of birth until day 90 in this research. Then evaluated the neurobehavioral changes in rats, observed the ultrastructural changes of hippocampal synapses and neurons, and examined the level of hippocampal acetylated histone H3 (H3ac), the activity and protein expression of hippocampal HAT1 and G9a, and the protein expression level of H3K9 dimethylation (H3K9me2). The findings demonstrated that aluminum-treated offspring rats had impaired learning and memory abilities as well as ultrastructural alterations in hippocampal synapses and neurons. The level of histone H3ac was decreased along with decreased protein expression and activity of HAT1, while level of H3K9me2 was increased along with increased protein expression and activity of G9a.

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Data Availability

This published article and its supplemental information file contain all data created or analyzed throughout this experiment.

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Acknowledgements

We would like to thank Dr. Lifeng Zhang for reading and editing of the manuscript thoroughly.

Funding

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

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  1. Jie Gao and Wei Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Maternal, Child and Adolescent Health, School of Public Health, Shenyang Medical College, Shenyang, 110034, Liaoning Province, P. R. China

    Jie Gao, Wei Liu, Jiaqi Liu, Ni** Hao, **g Pei & Lifeng Zhang

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Contributions

Author Contribution J.G, W.L and J.L designed and conducted the research; N.H and J.P performed the experiments; J.G and W.L analyzed the data and wrote the paper; J.G, W.L and L.Z reviewed and edited the manuscript. All authors edited and approved the final manuscript.

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Correspondence to Lifeng Zhang.

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All animal experiments were conducted in accordance with the ethical review protocol approved in advance by Shenyang Medical College.

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Gao, J., Liu, W., Liu, J. et al. The Role of Acetylation and Methylation of Rat Hippocampal Histone H3 in the Mechanism of Aluminum-Induced Neurotoxicity. Neurochem Res 49, 441–452 (2024). https://doi.org/10.1007/s11064-023-04045-0

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