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Aluminum-induced “mixed” cell death in mice cerebral tissue and potential intervention

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Abstract

The brain is one of organs vulnerable to aluminum insult. Aluminum toxicity is involved in neurobehavioral deficit, neuronal cell dysfunction, and death. The aim of this study are as follows: (1) to evaluate the repairing efficiency of Necrostatin-1 (Nec-1), a cell death inhibitor, and Z-VAD-FMK, a pan-caspase inhibitor, on Al-induced neurobehavioral deficit and neuronal cell death, in order to evidence the cell death inducing ability of aluminum, and (2) to primarily explore the possibility of treating neuronal cell loss–related disease, such as Alzheimer’s disease, with Nec-1 and Z-VAD in Al-induced dementia animal model. We found Nec-1 and Z-VAD-FMK alone or in combination could reduce aluminum-induced learning and memory impairment in mice. Pathohistological results indicated that Nec-1 and Z-VAD-FMK can decrease Al-induced neuronal death cell. In addition, some cell death–associated proteins in cell death signal pathway were inhibited by Nec-1 and Z-VAD-FMK in Al-exposed mice. In conclusions, Nec-1 and Z-VAD-FMK can repair the injury of learning and memory induced by aluminum in mice. Furthermore, Nec-1 was more obvious to repair the injury of learning and memory function compared with Z-VAD-FMK. Nec-1 and Z-VAD-FMK can repair the Al-induced morphological injury of cell and reduce the amounts of dead cell, and repairing effects were more significant at higher doses. The effect of Nec-1 was stronger than Z-VAD-FMK, though their mechanism was different. The combination of them had the strongest effect. Our study evidenced Al-induced neuronal necroptosis and apoptosis existing in animal model and suggested potential therapeutic effects of Nec-1 and Z-VAD-FMK on neuronal cell death in neurodegenerative diseases.

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Funding

This study was supported by the Natural Science Foundation of China (NSFC, 81430078).

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Authors and Affiliations

  1. Department of Occupational Health, Key Laboratory of Environmental Hazard and Health of Shanxi Province, Key Laboratory of Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China

    Yan-xia Hao, Mei-qin Li, Jing-si Zhang, Qin-li Zhang, Xia Jiao, Xiu-liang Ji, Huan Li & Qiao Niu

  2. Shanxi Provincial People’s Hospital, Taiyuan, People’s Republic of China

    Yan-xia Hao

  3. University of Mississippi Medical Center, 2500 N State Street, Jackson, MS, 39216, USA

    Qin-li Zhang

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  1. Yan-xia Hao
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  2. Mei-qin Li
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  3. Jing-si Zhang
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  4. Qin-li Zhang
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  5. Xia Jiao
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  6. Xiu-liang Ji
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  7. Huan Li
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  8. Qiao Niu
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Correspondence to Qiao Niu.

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This study was approved by the Ethics Committee for Animal Studies of Shanxi Medical University.

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Hao, Yx., Li, Mq., Zhang, Js. et al. Aluminum-induced “mixed” cell death in mice cerebral tissue and potential intervention. Neurotox Res 37, 835–846 (2020). https://doi.org/10.1007/s12640-019-00123-w

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  • DOI: https://doi.org/10.1007/s12640-019-00123-w

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