An Air Particulate Pollutant Induces Neuroinflammation and Neurodegeneration in Human Brain Models

Abstract

Fine particulate matter (PM2.5), a major component among air pollutants, highlights as a global health concern. Several epidemiological studies show the correlation between chronical PM2.5 exposure and incidents of neurological disorders including Alzheimer's disease. However, the mechanisms have not been well understood, partly due to the lack of model systems that reflect the physiologically relevant innate immunity in human brains. Here, PM2.5‐polluted human brain models (PMBs) are created in a 3D microfluidic platform reconstituting key aspects of human brain immunity under the PM2.5 exposure. PM2.5 penetration across a blood–brain barrier (BBB) model and accumulation in the brain tissue side of the model are first validated. Second, the PMB model shows that the BBB‐penetrating PM2.5 initiates astrogliosis, resulting in slight neuronal loss and microglial infiltration. Third, it is demonstrated that the infiltrating microglia obtain M1 phenotype induced by interleukin‐1β and interferon‐γ from neurons and reactive astrocytes under the PM2.5 exposure. Finally, it is observed that additional proinflammatory mediators and nitric oxide released from the M1 microglia exacerbate neuronal damages, such as synaptic impairment, phosphoric tau accumulation, and neuronal death. This study suggests that PM2.5 can be a potential environmental risk factor for dementia mediated by the detrimental neuroinflammation.

Particulate matter and Alzheimer’s disease: an intimate connection

“…The hippocampus is responsible for learning and memory processes and is implicated in AD development [34]. Studies have demonstrated the ability of PM to initiate neurological effects beyond the olfactory bulb and penetrate barriers within the body and brain [16,18,34]. Findings from TRAP-exposed animals support the hypothesis that PM nanoparticles can translocate to the brain, specifically the hippocampus, as exposed animals possessed visible refractive particles in the hippocampal region [34].…”

“…activation, systemic/neuroinflammation, oxidative stress, immune activation, and behavioral changes) have been found in PM-exposed animals [3,[16][17][18][19][20]. The following section will discuss clinical hallmarks of AD and associated changes in the context of PM exposure through clinical and preclinical studies to better understand PM exposures and AD development.…”

Long-Term Exposure to Fine Particulate Matter and the Risk of Chronic Liver Diseases: A Meta-Analysis of Observational Studies

“…Overexposure to PM2.5 pollution promoted the incidence and mortality of serious multi-system diseases including the respiratory system, cardiovascular systems, and digestive system. An increasing number of studies have proved that PM2.5 enters the blood circulation and deposits in liver, brain, and other organs through gas exchange in the alveolus [ 43 , 44 ]. Recent studies also reported that inhalation of PM2.5 disordered gut microbiota, leading to abnormal serum metabolome and insulin resistance [ 45 , 46 ].…”

Effects of microenvironmental factors on assessing nanoparticle toxicity

“…Recent studies have showed that an indirect toxic effect was induced in a multicellular environment by the inflammatory cytokine or oxidative stress produced by cells exposed to air pollutants. 185–187 Therefore, consideration of the coculture environment, especially with immune cells, is necessary to estimate particulate matter-induced tissue damage and cytotoxicity.…”