Ambient PM particles reach mouse brain, generate ultrastructural hallmarks of neuroinflammation, and stimulate amyloid deposition, tangles, and plaque formation

Abstract

Mice were exposed to ambient PM particles 8 h per day, 6 days per week, for twenty-four weeks in enrichment chambers, with real-time mass concentration of PM2.5 around 70 µg/m3, and the number of PM0.1 about 10,000-20,000/m3. The component analysis of PM particles by inductive coupled plasma emission spectrometer detected low concentrations of species associated with crustal materials, metalloid, transition metals, and heavy metals originating from industrial emission. High-performance liquid chromatography (HPLC) detected 22 polycyclic aromatic hydrocarbons originating from traffic exhausts. We found that PM particles from dirty air entered mouse brain which were visualized by field emission scanning electron microscopy (FE-SEM) and were counted by femtosecond pulsed laser illumination microscopy. FE-SEM of brain tissues from dirty air (n=8), and filtered air (control) (n=8) revealed ultrastructural hallmarks of neuroinflammation, enlarged perivascular space, and the attachment of inflammatory cells to the endothelium of blood vessels in brain. Exposure to dirty air containing ambient PM particles resulted in amyloid deposits and formation of neurofibrillary tangles and plaques. Desorption electrospray ionization mass spectrometry imaging enabled label-free elucidation of the spatial distribution of metabolites and lipids in brain tissue samples without any pretreatment. Ceramide Cer(t18:0/34:0(34OH)), m/z 822.54, and sulfatides, ST18:0, m/z 806.54; ST(d18:1/h22:0), m/z 878.60; ST(24:1), m/z 888.62, and ST(d18:1/h24:0), m/z 906.62 showed upregulation with significant differences in brain tissue from mice exposed to dirty air as compared to filtered air (control). The upregulation of ceramide resulted in formation of neurofibrillary tangles and plaques. Moreover, upregulation of sulfatides might enhance the leakiness of the blood brain barrier by weakening myelin sheaths. Although limited by sample number, our results strongly suggest that prolonged exposure to dirty air contributes to the observed increase in the incidence of cognitive decline and dementia, such as Alzheimer's disease.