Effects of oxidative stress on hepatic encephalopathy pathogenesis in mice.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37488119.
- Also identified by DOI 10.1038/s41467-023-40081-8 and PMC identifier 10366183.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 (SNr<sup>GAD2</sup>) is activated by HE. Both overexpression of mitochondrial uncoupling protein 2 (UCP2) targeted to SNr<sup>GAD2</sup> and SNr<sup>GAD2</sup>-targeted chemogenetic inhibition targeted to SNr<sup>GAD2</sup> rescue mitochondrial dysfunction in TAA-induced HE. These results define the key role of oxidative stress in the pathogenesis of HE.
Medical subject headings
- Hepatic Encephalopathy