Role of brain extracellular vesicles in air pollution-related cognitive impairment and neurodegeneration

Abstract

A relationship between environmental exposure to air pollution and cognitive impairment and neurological disorders has been described. Previous literature has focused on the direct effects of the air pollution components on neuronal and glial cells, as well as on involvement of oxidative stress and neuroinflammation on microglia and astrocyte reactivity. However, other mechanisms involved in the air pollution effects on central nervous system (CNS) toxicity can be playing critical roles. Increasingly, extracellular vesicle's (EVs) mediated intercellular communication is being recognized as impacting the development of cognitive impairment and neurological disorders like Alzheimer's disease and others. Here we describe the available evidence about toxic air pollutants and its components on brain, an involvement of brain cells specific and EVs types (based in the origin or in the size of EVs) in the initiation, exacerbation, and propagation of the neurotoxic effects (inflammation, neurodegeneration, and accumulation of neurotoxic proteins) induced by air pollution in the CNS. Additionally, we discuss the identification and isolation of neural-derived EVs from human plasma, the most common markers for neural-derived EVs, and their potential for use as diagnostic or therapeutic molecules for air pollution-related cognitive impairment and neurodegeneration.

Keywords: Air pollution; Cognitive impairment; Extracellular vesicles; Neurodegeneration; PM(2.5).

Figure 1.. Effect of Air Pollution on CNS Cells & EVs Release.

Air pollution triggers microglia activation and reactive astrocytes inducing neuronal inflammation/excitation and oligodendrocyte dysfunction. It results in the increased release of EVs from glial and neuronal cells. EVs can cross the BBB to enter the systemic circulation whereby, they may be isolated from blood/plasma and identified through centrifugation, filtering, or immunoprecipitation with cell-type specific antibodies for molecular analyses. PM_2.5: Particulate matter with diameter < 2.5 μm. (Allen et al., 2017; Chen et al., 2020; Liddelow et al., 2017)

Figure 2.. Effects and functions of EVs in the central nervous system.

A: Under physiological conditions, EVs help maintain brain homeostasis and neuronal function. However, under pathological conditions, EVs may promote inflammation, neurodegeneration, and myelin loss and serve as conduits for the intercellular spread and aggregation of neurotoxic proteins. B: Neurons release EVs that can contain tau protein or carry Aβ fibrils anchored apically to membrane-bound PrP^c. Microglia, astrocytes, and other neurons participate in the clearance and uptake of neuronal-derived EVs. C: EVs can seed the aggregation of extracellular free tau and Aβ, forming neurofibrillary tangles and plaques that activate microglia and promote microglial EV uptake.