Editor's Highlight: Nlrp3 Is Required for Inflammatory Changes and Nigral Cell Loss Resulting From Chronic Intragastric Rotenone Exposure in Mice.

Autor:	Martinez EM; Department of Molecular and Systems Biology., Young AL; Department of Molecular and Systems Biology., Patankar YR; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire 03756., Berwin BL; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire 03756., Wang L; Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226., von Herrmann KM; Department of Molecular and Systems Biology., Weier JM; Department of Molecular and Systems Biology., Havrda MC; Department of Molecular and Systems Biology.
Jazyk:	angličtina
Zdroj:	Toxicological sciences : an official journal of the Society of Toxicology [Toxicol Sci] 2017 Sep 01; Vol. 159 (1), pp. 64-75.
DOI:	10.1093/toxsci/kfx117
Abstrakt:	Complex interactions between genetic and environmental factors are widely believed to underlie the incidence and progression of Parkinson's disease (PD). Rotenone is a naturally occurring metabolic toxin employed as an insecticide and piscicide identified as a risk factor for the development of PD in agricultural workers. The Nlrp3 inflammasome is an intracellular mediator that can initiate an inflammatory cascade in response to cellular stress. Reports by others indicating that NLRP3 expression was detectable in tissues obtained from Alzheimer's disease patients and that the PD-associated protein α-synuclein could activate inflammasomes in cultured glial cells, prompted us to test the prediction that Nlrp3 was required for the development of Parkinson's-like changes resulting from rotenone exposure in mice. We exposed wild type and Nlrp3-/- mice to chronic low doses of intragastric rotenone and conducted longitudinal behavioral and serum cytokine analysis followed by evaluation of neuroinflammatory and neurodegenerative endpoints in brain tissues. We observed progressive rotenone-dependent changes in serum cytokine levels and circulating leukocytes in wild type mice not observed in Nlrp3-/- mice. Analysis of brain tissues revealed Nlrp3-dependent neuroinflammation and nigral cell loss in mice exposed to rotenone as compared with mice exposed to vehicle alone. Together, our findings provide compelling evidence of a role for Nlrp3 in nigral degeneration and neuroinflammation resulting from systemic rotenone exposure and suggest that the suppression of NLRP3 activity may be a rational neuroprotective strategy for toxin-associated PD. (© The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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