Mitochondria-A target for attenuation of astrocyte pathology

J Neuroimmunol. 2021 Sep 15:358:577657. doi: 10.1016/j.jneuroim.2021.577657. Epub 2021 Jul 14.

Abstract

Astrocyte pathology is a feature of neuromyelitis optica spectrum disorder (NMOSD) pathology. Recently mitochondrial dysfunction and metabolic changes were suggested to play a role in NMOSD. To elucidate the role of mitochondrial dysfunction, astrocyte pathology was induced in C57BL/6 J female mice by intracerebral injection of aquaporin-4-immunoglobulin G from an NMOSD patient, together with complement. Etomoxir has been shown to cause mitochondrial dysfunction. Etomoxir was delivered to the central nervous system and resulted in decreased astrocyte pathology. The ameliorating effect was associated with increases in different acylcarnitines and amino acids. This suggests that mitochondria may be a therapeutic target in NMOSD.

Keywords: Astrocyte pathology; Central nervous system; Etomoxir; Metabolic; Mitochondrial dysfunction; Neuromyelitis optica spectrum disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Astrocytes / immunology*
  • Astrocytes / pathology*
  • Autoantibodies / immunology*
  • Epoxy Compounds / administration & dosage*
  • Female
  • Humans
  • Immunoglobulin G / administration & dosage
  • Immunoglobulin G / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects
  • Mitochondria / immunology*
  • Neuromyelitis Optica / immunology

Substances

  • Autoantibodies
  • Epoxy Compounds
  • Immunoglobulin G
  • etomoxir