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Electroacupuncture Ameliorates Cognitive Impairment Through the Inhibition of NLRP3 Inflammasome Activation by Regulating Melatonin-Mediated Mitophagy in Stroke Rats

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Abstract

Previous studies found that electroacupuncture (EA) at the Shenting (DU24) and Baihui (DU20) acupoints alleviates cognitive impairment in cerebral ischemia–reperfusion (I/R) injury rats. Nonetheless, the mechanisms of the anti-inflammatory effects of EA are unclear. Cerebral I/R injury was induced in rats by middle cerebral artery occlusion (MCAO). Following I/R injury, the rats underwent EA therapy at the Shenting (DU24) and Baihui (DU20) acupoints for seven successive days. The Morris water maze test, magnetic resonance imaging (MRI) and molecular biology assays were utilized to assess the establishment of the rat stroke model with cognitive impairment and the therapeutic effect of EA. EA treatment of rats subjected to MCAO showed a significant reduction in infarct volumes accompanied by cognitive recovery, as observed in Morris water maze test outcomes. The possible mechanisms by which EA treatment attenuates cognitive impairment are by regulating endogenous melatonin secretion through aralkylamine N-acetyltransferase gene (AANAT, a rate-limiting enzyme of melatonin) synthesis in the pineal gland in stroke rats. Simultaneously, through melatonin regulation, EA exerts neuroprotective effects by upregulating mitophagy-associated proteins and suppressing reactive oxygen species (ROS)-induced NLRP3 inflammasome activation after I/R injury. However, melatonin receptor inhibitor (luzindole) treatment reversed these changes. The findings from this research suggested that EA ameliorates cognitive impairment through the inhibition of NLRP3 inflammasome activation by regulating melatonin-mediated mitophagy in stroke rats.

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Acknowledgements

We would like to thank AJE (www.aje.cn) for English language editing.

Funding

This study was supported by the National Natural Science Foundation of China (Grant Nos. 81803889 and 81804175), the Natural Science Foundation of Fujian Province (Grant Nos. 2018J01329, 2019J01497, and 2020J011043), and the National Traditional Chinese Medicine (TCM) Clinical Research Base Foundation of Fujian (Grant No. JDZX2019043).

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Authors and Affiliations

  1. Neurology Department, The Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, 350004, China

    Xiaoyong Zhong, Su Ruan, Fang Wang & Hui Liang

  2. National Clinical Research Base of Traditional Chinese Medicine, the Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, 350004, China

    Xiaoyong Zhong & Bin Chen

  3. Department of Rehabilitation, The Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, 350004, China

    Bin Chen

  4. Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, China

    Zuanfang Li & Ruhui Lin

  5. College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China

    Jing Tao

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  1. Xiaoyong Zhong
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  2. Bin Chen
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  3. Zuanfang Li
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Contributions

XZ Conceptualization, Methodology, Performed the experiment, Writing- Original draft preparation, analysis, Reviewing and Editing. BC, ZL and RL Performed the experiment, data analyses. HL, SR and FW Project administration, Data Curation and analysis. JT Conceptualization, Supervision.

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Correspondence to Xiaoyong Zhong or Jing Tao.

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Zhong, X., Chen, B., Li, Z. et al. Electroacupuncture Ameliorates Cognitive Impairment Through the Inhibition of NLRP3 Inflammasome Activation by Regulating Melatonin-Mediated Mitophagy in Stroke Rats. Neurochem Res 47, 1917–1930 (2022). https://doi.org/10.1007/s11064-022-03575-3

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