Systemic Exposure to Air Pollution Induces Oxidative Stress and Inflammation in Mouse Brain, Contributing to Neurodegeneration Onset.

Chiara Milani,Elisabetta Donzelli,Elisa Ballarini,Alessandra Bulbarelli,Luca Crippa,Paola Palestini,Luca Massimino,Paola Marmiroli,Elena Lonati,Laura Botto,Francesca Farina

doi:10.3390/ijms21103699

Abstract

In northern Italy, biomass burning-derived (BB) particles and diesel exhaust particles (DEP) are considered the most significant contributors to ultrafine particle (UFP) emission. However, a comparison between their impact on different brain regions was not investigated until now. Therefore, male BALB/c mice were treated with a single or three consecutive intratracheal instillations using 50 µg of UFPs in 100 µL of isotonic saline solution or 100 µL of isotonic saline solution alone, and brains were collected and analyzed. Proteins related to oxidative stress and inflammation, as well as Alzheimer’s disease markers, were examined in the hippocampus, cerebellum, and the rest of the brain (RoB). Histopathological examination of the brain was also performed. Moreover, correlations among different brain, pulmonary, and cardiovascular markers were performed, allowing us to identify the potentially most stressful UFP source. Although both acute exposures induced inflammatory pathways in mouse brain, only DEP showed strong oxidative stress. The sub-acute exposure also induced the modulation of APP and BACE1 protein levels for both UFPs. We observed that DEP exposure is more harmful than BB, and this different response could be explained by this UFP’s different chemical composition and reactivity.

Highlights

Airborne particulate matter (PM) is a complex mixture of solid and liquid particles with different size, composition, and origin, suspended in the air [1]
After acute diesel exhaust particles (DEP) exposure, we observed a significant increase in Hsp70 levels in the rest of the brain (RoB), which positively correlates with several markers, including heme oxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS) expressed in the same brain areas, and Hsp70 and MPO increased in the heart and bronchoalveolar lavage fluid (BALf) [33]
We demonstrated that amyloidogenic precursor protein (APP) and BACE1 protein levels undergo some alterations after biomass burning-derived (BB) and DEP sub-acute exposure, and we hypothesize that these changes may become more prominent during chronic exposure, as demonstrated by mouse long-term PM inhalation performed by Bhatt and collaborators [64]

Summary

Introduction

Airborne particulate matter (PM) is a complex mixture of solid and liquid particles with different size, composition, and origin, suspended in the air [1]. In Lombardy (northern Italy), solid biomass burning for domestic heating and diesel combustion used for private and public transport are estimated to be the major sources of fine particle emissions (PM2.5, da < 2.5 μm), accounting for 49.8% and 21.5%, respectively [6,7,8]. Biomass burning and diesel combustion mainly produce particles of 15–30 nm in diameter, often aggregated; these processes are considered significant contributors to UFP emission [9,10]. During the last few years, the use of biomass burning for residential heating experienced a substantial increase in northern Italy and Europe as a result of the affordable price of solid biomass fuels and as a consequence of the policy that aims to reduce greenhouse gases (EU Directive, 2009/287/EC). The result is a relatively high UFP emission, which contains a multitude of toxic or carcinogenic compounds, including free radicals, polycyclic aromatic hydrocarbons (PAHs), and aldehydes [12]

Methods

Results

Conclusion