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Part Fibre Toxicol. 2017 Aug 30;14(1):35. doi: 10.1186/s12989-017-0213-5.

Diesel engine exhaust accelerates plaque formation in a mouse model of Alzheimer's disease.

Author information

1
IUF - Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225, Düsseldorf, Germany.
2
, Present address: Triskelion BV Utrechtseweg 48, 3704 HE, Zeist, The Netherlands.
3
National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
4
Department of Pharmacology and Toxicology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
5
Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
6
Institute of Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
7
Department of Psychiatry and Psychotherapy, Division of Molecular Psychiatry, Georg-August-University Göttingen, University Medicine Göttingen, Göttingen, Germany.
8
IUF - Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225, Düsseldorf, Germany. Roel.Schins@uni-duesseldorf.de.

Abstract

BACKGROUND:

Increasing evidence from toxicological and epidemiological studies indicates that the central nervous system is an important target for ambient air pollutants. We have investigated whether long-term inhalation exposure to diesel engine exhaust (DEE), a dominant contributor to particulate air pollution in urban environments, can aggravate Alzheimer's Disease (AD)-like effects in female 5X Familial AD (5XFAD) mice and their wild-type female littermates. Following 3 and 13 weeks exposures to diluted DEE (0.95 mg/m3, 6 h/day, 5 days/week) or clean air (controls) behaviour tests were performed and amyloid-β (Aβ) plaque formation, pulmonary histopathology and systemic inflammation were evaluated.

RESULTS:

In a string suspension task, assessing for grip strength and motor coordination, 13 weeks exposed 5XFAD mice performed significantly less than the 5XFAD controls. Spatial working memory deficits, assessed by Y-maze and X-maze tasks, were not observed in association with the DEE exposures. Brains of the 3 weeks DEE-exposed 5XFAD mice showed significantly higher cortical Aβ plaque load and higher whole brain homogenate Aβ42 levels than the clean air-exposed 5XFAD littermate controls. After the 13 weeks exposures, with increasing age and progression of the AD-phenotype of the 5XFAD mice, DEE-related differences in amyloid pathology were no longer present. Immunohistochemical evaluation of lungs of the mice revealed no obvious genetic background-related differences in tissue structure, and the DEE exposure did not cause histopathological changes in the mice of both backgrounds. Luminex analysis of plasma cytokines demonstrated absence of sustained systemic inflammation upon DEE exposure.

CONCLUSIONS:

Inhalation exposure to DEE causes accelerated plaque formation and motor function impairment in 5XFAD transgenic mice. Our study provides further support that the brain is a relevant target for the effects of inhaled DEE and suggests that long-term exposure to this ubiquitous air pollution mixture may promote the development of Alzheimer's disease.

KEYWORDS:

5XFAD mice; Alzheimer’s disease; Amyloid-β; Behaviour; Diesel engine exhaust; Inhalation; Particulate matter

PMID:
28854940
PMCID:
PMC5577845
DOI:
10.1186/s12989-017-0213-5
[Indexed for MEDLINE]
Free PMC Article

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