Oral glutathione administration inhibits the oxidative stress and the inflammatory responses in AppNL−G-F/NL−G-F knock-in mice

Hisanao Izumi, Keita Sato, Kazuhiro Kojima, Takashi Saito, Takaomi C. Saido, Kohji Fukunaga

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by the presence of extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles. Reduced antioxidants and increased oxidative stress and inflammation are responsible for the pathological features characteristic of an AD brain. We observed decreased levels of the reduced form of glutathione (GSH), the most abundant brain antioxidant, and decreased GSH/glutathione disulfide (GSSG) ratios in AppNL−G-F/NL−G-F knock-in (NL-G-F) mouse brains. Repeated oral GSH administration for 3 weeks dose-dependently increased GSH levels and restored the GSH/GSSH ratio. Consistent with the restoration of GSH levels, the levels of 4-hydroxy-2-nonenal (4-HNE), a marker of oxidative stress, were significantly decreased in the hippocampus of NL-G-F mice. Additionally, inflammatory responses, such as microgliosis and increased mRNA expression of inflammatory cytokines, were also inhibited. Moreover, behavioral deficits including cognitive decline, depressive-like behaviors, and anxiety-related behaviors observed in NL-G-F mice were significantly improved by oral and chronic GSH administration. Taken together, our data suggest that oral GSH administration is an attractive therapeutic strategy to reduce the excessive oxidative stress and inflammatory responses in the AD brain.

Original languageEnglish
Article number108026
JournalNeuropharmacology
Volume168
DOIs
Publication statusPublished - 2020 May 15

Keywords

  • Alzheimer's disease
  • Glutathione
  • Inflammation
  • Oxidative stress

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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