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Protective effects of dihydromyricetin on primary hippocampal astrocytes from cytotoxicity induced by comorbid diabetic neuropathic pain and depression

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Abstract

Activated astrocytes play a key role in diabetic neuropathic pain and depression. We aimed to assess the protective effects of dihydromyricetin (DHM) on primary hippocampal astrocytes cultured with high glucose (HG), substance P (SP), and corticosterone (CORT). Culturing with HG + SP + CORT resulted in damage to primary hippocampal astrocytes, which simulates the clinical damage caused by comorbidity of diabetic neuropathic pain and depression. Western blot, qPCR, and immunofluorescence analyses revealed that HG + SP + CORT increased P2X7 receptor expression in primary hippocampal astrocytes, which was reversed by DHM treatment. Further, HG + SP + CORT elevated TNF-α, IL-1β, free Ca2+, and ERK1/2 phosphorylation levels, which was inhibited by DHM or P2X7 shRNA treatment. Moreover, DHM significantly reduced the P2X7 agonist-activated currents in HEK293 cells transfected with the P2X7 receptor. These findings suggest that DHM can protect primary hippocampal astrocytes cultured with HG + SP + CORT from P2X7 receptor-mediated damage. Culturing cells with HG + SP + CORT might be a viable cell model for cellular injury exploration of diabetic comorbid pain and depression.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgments

We thank Prof. Shangdong Liang and Prof. Guodong Li for assisting us in the experimental design.

Funding

This study was supported by grants from the National Natural Science Foundation of China (No. 81760152).

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Authors and Affiliations

  1. Department of Physiology, Basic Medical College of Nanchang University, 461 Bayi Road, Nanchang, Jiangxi, China

    Huixiang Ge, Mengyun Sun, Mingming Zhang & Yun Gao

  2. Medical College of Grade 2017, Nanchang University, Nanchang, Jiangxi, People’s Republic of China

    Xingyu Wei, Ruxin Chen & Miao Ye

  3. Medical College of Grade 2018, Nanchang University, Nanchang, Jiangxi, People’s Republic of China

    Hongcheng Tu

  4. Queen Mary College of Grade 2016, Nanchang University, Nanchang, Jiangxi, People’s Republic of China

    Yuanzhen Hao

  5. Jiangxi Provincial Key Laboratory of Autonomic Nervous Function and Disease, Nanchang, Jiangxi, People’s Republic of China

    Yun Gao

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Contributions

Y.G. designed the study; H.G. and M.S. carried out the experiments; X. W., M. Z., H.T., Y. H., R.C., and M.Y. assisted H.G to carry out the findings; H.G. drafted the manuscript and all authors reviewed the manuscript and approved the final version for publication.

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Correspondence to Yun Gao.

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The authors declare that they have no financial or other conflicts of interest in association with this work.

Ethical approval

This study was approved by the Animal Care and Ethics Committee of Nanchang University. We performed the experiments in accordance with the guidelines of the National Institutes of Health on Laboratory Animal Care and Use (NIH Publication No. 8023, Rev. 1978).

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Ge, H., Sun, M., Wei, X. et al. Protective effects of dihydromyricetin on primary hippocampal astrocytes from cytotoxicity induced by comorbid diabetic neuropathic pain and depression. Purinergic Signalling 16, 585–599 (2020). https://doi.org/10.1007/s11302-020-09752-9

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