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 journalArticlepeer-review

56 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 H2O2, 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

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

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