Regulatory doses of fungicides in water exacerbate Alzheimer's markers

Pierre-André Lafon, Yunyun Wang, Margarita Arango-Lievano, Joan Torrent, Lucie Salvador-Prince, Marine Mansuy, Nadine Mestre-Francès, Laurent Givalois, Jianfeng Liu, Josep Vicent Mercader, Freddy Jeanneteau, Catherine Desrumaux, Véronique Perrier

Overview

Our environment is contaminated by multiple pesticide residues whose long-term impact on health is subject to debate and concern. In order to mimic this chronic low-noise exposure, we treated transgenic mice model of Alzheimer's disease, with a cocktail of 3 fungicides (cyprodinil, mepanipyrim and pyrimethanil) at the regulatory dose of 0.1 ?g / L, present in drinking water.

Summary

Our results showed that chronic exposure to fungicides, even at very low doses, exacerbates markers of Alzheimer's disease such as amyloid deposits, inflammation and neuronal cell death.

Resources

Des fongicides aggravent Alzheimer chez la souris
https://www.lemonde.fr/sciences/article/2020/03/03/des-fongicides-aggravent-alzheimer-chez-la-souris_6031661_1650684.html
Maladie d’Alzheimer: des fongicides impliqués?
http://www.journaldelenvironnement.net/article/maladie-d-alzheimer-des-fongicides-impliques,103336
Des doses réglementaires de fongicides dans l’eau exacerbent les marqueurs d’Alzheimer
https://insb.cnrs.fr/fr/cnrsinfo/des-doses-reglementaires-de-fongicides-dans-leau-exacerbent-les-marqueurs-dalzheimer

Fungicide Residues Exposure and Aggregation in a Mouse Model of Alzheimer's Disease.

Authors:
Dr Pierre-Andre Lafon, Ph.D.
Dr Pierre-Andre Lafon, Ph.D.
Huazhong University od Science and Technology, College of Life Science and Technology, Cell Signaling lab
Doctor
Prion diseases, Alzheimer's disease, pesticides
Wuhan, Hubei | China

Environ Health Perspect 2020 Jan 15;128(1):17011. Epub 2020 Jan 15.

MMDN, University of Montpellier, EPHE, INSERM, Montpellier, France.

Background: Pesticide residues have contaminated our environment and nutrition over the last century. Although these compounds are present at very low concentrations, their long-term effects on human health is of concern. The link between pesticide residues and Alzheimer's disease is not clear and difficult to establish. To date, no experiments have yet modeled the impact of this chronic contamination on neurodegenerative disorders.

Objectives: We investigated the impact of fungicide residues on the pathological markers of Alzheimer's disease in a transgenic mouse model.

Methods: Transgenic (J20, ) mice were chronically exposed to a cocktail of residues of cyprodinil, mepanipyrim, and pyrimethanil at in their drinking water for 9 months. We assessed the effects of fungicide residues on the pathological markers of the disease including aggregates, neuroinflammation, and neuronal loss. Then, we studied the dynamics of aggregation via a longitudinal study using two-photon microscopy. Finally, we investigated the molecular mechanisms involved in the production and clearance of peptides.

Results: We found that a chronic exposure to three fungicide residues exacerbated aggregation, microgliosis, and neuronal loss. These fungicides also increased vascular amyloid aggregates reminiscent of cerebral amyloid angiopathy between 6 and 9 months of treatment. The mechanism of action revealed that fungicides promoted peptide fibril formation and involved an overexpression of the levels of the -cleaving enzyme (BACE1) combined with impairment of clearance through neprylisin (NEP).

Conclusions: Chronic exposure of the J20 mouse model of Alzheimer's disease to a cocktail of fungicides, at the regulatory concentration allowed in tap water (), strengthened the preexisting pathological markers: neuroinflammation, aggregation, and APP . We hypothesize prevention strategies toward pesticide long-term exposure may be an alternative to counterbalance the lack of treatment and to slow down the worldwide Alzheimer's epidemic. https://doi.org/10.1289/EHP5550.

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Source
http://dx.doi.org/10.1289/EHP5550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015540PMC
January 2020
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