Continuous exposure to urban air pollution induces brain oxidative stress, inflammation and impaired mitochondrial function in mice

Abstract

Increasing evidence indicates that the central nervous system (CNS) is a target of air pollution, which might lead to oxidative stress and neuroinflammation. However, the mechanisms mediating these effects have not been fully elucidated. The aim of this work was to study the effects of chronic exposure to air pollution, on mice brain cortex (CX) and olfactory bulb (OB), focusing on oxidative and inflammatory markers, and mitochondrial function. Male 8-week-old BALB/c mice were exposed to filtered air (FA, control) or urban air (UA) inside whole-body inhalation chambers located in a highly polluted area of Buenos Aires City, for up to 4 weeks. Glutathione levels, assessed as GSH/GSSG ratio, were decreased in CX after 1 and 2 w of exposure to UA, and after 4 w in the case of the OB (26% and 60% respectively; p<0.05). NADPH oxidase and GPx activities were increased in all of the studied time points, while this increment was observed only after 4 w for SOD and GR activities, in CX of UA group (p<0.05). After 4 w, increased GFAP expression levels showed reactive astrocytes in OB, probably associated with the altered olfactory function observed by a behavioral test, in UA compared to FA mice (p<0.05). Also, UA mice showed impaired mitochondrial function due to a 50% reduction in O2 consumption in active state (state 3) (p<0.05), a 65% decrease in ATP production rate (p<0.01) and a 30% increase of H2O2 production (p<0.01). Moreover, respiratory complexes I-III and II-III activities were decreased in UA group (30% and 36% respectively vs. FA; p<0.05). Taken together, UA exposed mice showed alterations in mice olfaction and mitochondrial function, increased oxidants production, along with an inflammatory process evidenced by astrocyte activation. These data indicate that oxidative stress and inflammation may play a key role in CNS damage mechanisms, triggered by air pollution.