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 language | English (US) |
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Pages (from-to) | 2533-2543 |
Number of pages | 11 |
Journal | Neurobiology of Aging |
Volume | 36 |
Issue number | 9 |
DOIs | |
State | Published - Sep 1 2015 |
Keywords
- Alzheimer's disease
- Aβ
- Inflammation
- Mitochondria
- NLRP3 inflammasome
- Oxidative stress
- Paraquat
- Toxin exposure
ASJC Scopus subject areas
- Clinical Neurology
- Neuroscience(all)
- Aging
- Developmental Biology
- Geriatrics and Gerontology