Enhanced defense against mitochondrial hydrogen peroxide attenuates age-associated cognition decline

Liuji Chen, Ren Na, Qitao Ran

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Increased mitochondrial hydrogen peroxide (H2O2) is associated with Alzheimer's disease and brain aging. Peroxiredoxin 3 (Prdx3) is the key mitochondrial antioxidant defense enzyme in detoxifying H2O2. To investigate the importance of mitochondrial H2O2 in age-associated cognitive decline, we compared cognition between aged (17-19months) APP transgenic mice and APP/Prdx3 double transgenic mice (dTG) and between old (24months) wild-type mice and Prdx3 transgenic mice (TG). Compared with aged APP mice, aged dTG mice showed improved cognition that was correlated with reduced brain amyloid beta levels and decreased amyloid beta production. Old TG mice also showed significantly increased cognitive ability compared with old wild-type mice. Both aged dTG mice and old TG mice had reduced mitochondrial oxidative stress and increased mitochondrial function. Moreover, CREB signaling, a signaling pathway important for cognition was enhanced in both aged dTG mice and old TG mice. Thus, our results indicate that mitochondrial H2O2 is a key culprit of age-associated cognitive impairment, and that a reduction of mitochondrial H2O2 could improve cognition by maintaining mitochondrial health and enhancing CREB signaling.

Original languageEnglish (US)
Pages (from-to)2552-2561
Number of pages10
JournalNeurobiology of Aging
Volume35
Issue number11
DOIs
StatePublished - Nov 1 2014

Fingerprint

Cognition
Hydrogen Peroxide
Transgenic Mice
Peroxiredoxin III
Amyloid
Aptitude
Brain
Alzheimer Disease
Oxidative Stress
Antioxidants
Health
Enzymes

Keywords

  • Alzheimer's disease
  • Beta-amyloid
  • Brain aging
  • Mitochondria
  • Mitochondrial HO
  • Oxidative stress
  • Peroxiredoxin 3

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Enhanced defense against mitochondrial hydrogen peroxide attenuates age-associated cognition decline. / Chen, Liuji; Na, Ren; Ran, Qitao.

In: Neurobiology of Aging, Vol. 35, No. 11, 01.11.2014, p. 2552-2561.

Research output: Contribution to journalArticle

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