Progesterone reduces brain mitochondrial dysfunction after transient focal ischemia in male and female mice

J Cereb Blood Flow Metab. 2016 Mar;36(3):562-8. doi: 10.1177/0271678X15610338. Epub 2015 Oct 14.

Abstract

This study investigated the effect of intranasal administration of progesterone on the early brain mitochondrial respiratory chain dysfunction and oxidative damage after transient middle cerebral occlusion in male and female mice. We showed that progesterone (8 mg/kg at 1 h post-middle cerebral occlusion) restored the mitochondrial reduced glutathione pool and the nicotinamide adenine dinucleotide-linked respiration in both sexes. Progesterone also reversed the decrease of the flavin adenine dinucleotide-linked respiration, which was only observed in females. Our findings point to a sex difference in stroke effects on the brain respiratory chain and suggest that the actions of progesterone on mitochondrial function may participate in its neuroprotective properties.

Keywords: Mitochondria; oxidative phosphorylation; oxidative stress; progesterone; sex difference.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Cell Respiration / drug effects
  • Female
  • Flavin-Adenine Dinucleotide / analogs & derivatives
  • Flavin-Adenine Dinucleotide / metabolism
  • Glutathione / metabolism
  • Infarction, Middle Cerebral Artery / drug therapy*
  • Infarction, Middle Cerebral Artery / metabolism
  • Infarction, Middle Cerebral Artery / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • NAD / metabolism
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / therapeutic use*
  • Oxidative Stress / drug effects*
  • Oxygen Consumption / drug effects
  • Progesterone / administration & dosage
  • Progesterone / therapeutic use*

Substances

  • Neuroprotective Agents
  • NAD
  • Flavin-Adenine Dinucleotide
  • 1,5-dihydro-FAD
  • Progesterone
  • Glutathione