The Changes of Mitochondria in Substantia Nigra and Anterior Cerebral Cortex of Hepatic Encephalopathy Induced by Thioacetamide

Anat Rec (Hoboken). 2019 Jul;302(7):1169-1177. doi: 10.1002/ar.23932. Epub 2019 Mar 4.

Abstract

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome resulting from chronic or acute liver failure. Under the condition of HE, various factors such as reactive oxygen species, inflammatory factors, ammonia poisoning and amino acids alteration lead to changes of mitochondria. Selective depletion of damaged mitochondrion is essential for maintaining the morphology and function of mitochondria and cells. In this study, molecular biology analysis was used to analyze the mitochondrial morphology in the substantia nigra (SN) and anterior cerebral cortex (ACC) of the HE mice. The results revealed that the drp1, mfn1 and mfn2 increased in mRNA level of SN, which indicated the changes of mitochondrial morphology in HE mice. The drp1 and mfn2 genes were up-regulated, then, the Opa1 exhibited no significant change in the ACC of HE mice. Further study demonstrated that the mitochondrial autophagy related genes, pink1 and parkin, increased in SN, while the parkin reduced in ACC of HE mice. In addition, uncoupling protein (ucp2) increased in mRNA level of SN and ACC, and the ucp4 had no change or reduced in SN and ACC, respectively. These findings suggested that the mitochondrial dynamics is different in the SN and ACC of HE mice. Therefore, our results indicated that mitochondrial dynamics provided a potential treatment strategy for HE through the fission, fusion and autophagy of genes. Anat Rec, 302:1169-1177, 2019. © 2018 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.

Keywords: anterior cerebral cortex; hepatic encephalopathy; mitochondria; substantia nigra; thioacetamide.

MeSH terms

  • Animals
  • Autophagy
  • Cerebral Cortex / cytology
  • Cerebral Cortex / pathology*
  • Disease Models, Animal
  • Hepatic Encephalopathy / chemically induced
  • Hepatic Encephalopathy / pathology*
  • Humans
  • Injections, Intraperitoneal
  • Male
  • Mice
  • Mitochondria / pathology*
  • Mitochondrial Dynamics
  • Substantia Nigra / cytology
  • Substantia Nigra / pathology*
  • Thioacetamide / administration & dosage
  • Thioacetamide / toxicity

Substances

  • Thioacetamide