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Effects of oxidative stress on hepatic encephalopathy pathogenesis in mice

Author

Listed:
  • Yunhu Bai

    (The Fourth Military Medical University
    988 Hospital of Joint Logistic Support Force)

  • Kenan Li

    (The Fourth Military Medical University)

  • Xiaodong Li

    (The Fourth Military Medical University)

  • Xiyu Chen

    (The Fourth Military Medical University)

  • Jie Zheng

    (The Fourth Military Medical University)

  • Feifei Wu

    (The Fourth Military Medical University)

  • Jinghao Chen

    (The Fourth Military Medical University)

  • Ze Li

    (The Fourth Military Medical University)

  • Shuai Zhang

    (The Fourth Military Medical University)

  • Kun Wu

    (518 Hospital)

  • Yong Chen

    (The Fourth Military Medical University)

  • Yayun Wang

    (The Fourth Military Medical University)

  • Yanling Yang

    (The Fourth Military Medical University)

Abstract

Oxidative stress plays a crucial role in the pathogenesis of hepatic encephalopathy (HE), but the mechanism remains unclear. GABAergic neurons in substantia nigra pars reticulata (SNr) contribute to the motor deficit of HE. The present study aims to investigate the effects of oxidative stress on HE in male mice. The results validate the existence of oxidative stress in both liver and SNr across two murine models of HE induced by thioacetamide (TAA) and bile duct ligation (BDL). Systemic mitochondria-targeted antioxidative drug mitoquinone (Mito-Q) rescues mitochondrial dysfunction and oxidative injury in SNr, so as to restore the locomotor impairment in TAA and BDL mice. Furthermore, the GAD2-expressing SNr population (SNrGAD2) is activated by HE. Both overexpression of mitochondrial uncoupling protein 2 (UCP2) targeted to SNrGAD2 and SNrGAD2-targeted chemogenetic inhibition targeted to SNrGAD2 rescue mitochondrial dysfunction in TAA-induced HE. These results define the key role of oxidative stress in the pathogenesis of HE.

Suggested Citation

  • Yunhu Bai & Kenan Li & Xiaodong Li & Xiyu Chen & Jie Zheng & Feifei Wu & Jinghao Chen & Ze Li & Shuai Zhang & Kun Wu & Yong Chen & Yayun Wang & Yanling Yang, 2023. "Effects of oxidative stress on hepatic encephalopathy pathogenesis in mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40081-8
    DOI: 10.1038/s41467-023-40081-8
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    References listed on IDEAS

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    1. Bin Chen & Cenglin Xu & Yi Wang & Wenkai Lin & Ying Wang & Liying Chen & Heming Cheng & Lingyu Xu & Tingting Hu & Junli Zhao & Ping Dong & Yi Guo & Shihong Zhang & Shuang Wang & Yudong Zhou & Weiwei H, 2020. "A disinhibitory nigra-parafascicular pathway amplifies seizure in temporal lobe epilepsy," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
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