NLRP3 inflammasome activation by mitochondrial reactive oxygen species plays a key role in long-term cognitive impairment induced by paraquat exposure

Liuji Chen, Ren Na, Erin Boldt, Qitao Ran

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Exposure to environmental toxins such as pesticides is implicated in increasing Alzheimer's disease risk. In this study, we investigated the long-term effects of paraquat exposure on cognition of Alzheimer's disease animal model APP/PS1 mice and wild-type (WT) mice. Our results showed that APP/PS1 mice had exacerbated cognition impairment and elevated Aβ levels at 5months after paraquat exposure, and that WT mice had cognition impairment at 5 and 16months after paraquat exposure. In addition, increased mitochondrial oxidative stress and augmented brain inflammation were observed in both paraquat-exposed APP/PS1 mice and WT mice. Interestingly, activation of NLRP3 inflammasome, which triggers inflammation in response to mitochondrial stress, was enhanced in paraquat-exposed mice. Moreover, transgenic mice overexpressing Prdx3, a key enzyme in detoxifying mitochondrial H<inf>2</inf>O<inf>2</inf>, had suppressed NLRP3 inflammasome activation, reduced brain inflammation, and attenuated cognition impairment after paraquat exposure. Together, our results indicate that NLRP3 inflammasome activation induced by mitochondrial reactive oxygen species plays a key role in mediating paraquat-induced long-term cognition decline by elevating brain inflammation.

Original languageEnglish (US)
Pages (from-to)2533-2543
Number of pages11
JournalNeurobiology of Aging
Volume36
Issue number9
DOIs
StatePublished - Sep 1 2015

Keywords

  • Alzheimer's disease
  • Inflammation
  • Mitochondria
  • NLRP3 inflammasome
  • Oxidative stress
  • Paraquat
  • Toxin exposure

ASJC Scopus subject areas

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

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