Objective: To evaluate the impact of air pollution on microglial activation and phenotype and determine whether these changes persist following air quality improvement.

Background: Epidemiological evidence indicates that air pollution exposure significantly increases the risk of neurodegenerative diseases, including Parkinson’s Disease (PD) and other α-synucleinopathies [1]. Chronic microglial activation and a neuroinflammatory state have been implicated as mechanisms of PD pathogenesis and progression [2]. However, it remains unclear whether air quality improvements can mitigate these effects. Understanding the persistence of microglial activation and its inflammatory profile after pollution exposure may offer important insights into PD development.

Method: 8-week-old male and female C57BL/6 mice inhaled Filtered Air (FA) and DEP (NIST SRM 2975) at 100μg/m3. The three arms were 1) 8 weeks of FA or DEP, 2) 8 weeks of FA or DEP followed by an 8-week recovery period with FA, and 3) 16 weeks of FA or DEP (n=16/group). Immunofluorescence was conducted on corpus callosum tissue. Microglial activation was assessed using calcium-binding adapter molecule 1 (Iba-1). Proinflammatory microglia were identified with co-localization of Iba-1 with inducible nitric oxide synthase (iNOS), and anti-inflammatory microglia were identified with co-localization of Iba-1 with arginase-1 (Arg).

Results: Iba-1 expression elevated after 8 and 16 weeks of DEP exposure (+29%, p<0.0001 and +21%, p<0.01, respectively). Iba-1 elevation persisted after an 8-week recovery interval (+23%, p<0.001). Iba/iNos co-expression increased after 8 and 16 weeks of DEP exposure (+33%, p=0.009 and +23%, p=0.03, respectively). There was no increase in the 8-week recovery arm. No significant differences were observed in Iba-1/Arg co-expression across conditions [figure1].

Conclusion: DEP activation of microglia was robust after 8 weeks and 16 weeks of exposure and results in a primarily proinflammatory phenotype. Although microglial activation persists in the recovery phase, the proinflammatory phenotype is not sustained. These findings highlight air pollution as a modifiable environmental risk factor for PD and emphasize the need for further research on microglia-mediated neurodegenerative processes.

Previously presented in part at Congress of Neurological Surgeons Conference 9/30/24 and American Association of Neurological Surgeons Conference 4/25/25.

Figure 1: Corpus Callosum Immunofluorescence

References: [1] Murata H, Barnhill LM, Bronstein JM. Air Pollution and the Risk of Parkinson’s Disease: A Review. Mov Disord. 2022 May;37(5):894-904. doi: 10.1002/mds.28922. Epub 2022 Jan 19. PMID: 35043999; PMCID: PMC9119911.
[2] Isik S, Yeman Kiyak B, Akbayir R, Seyhali R, Arpaci T. Microglia Mediated Neuroinflammation in Parkinson’s Disease. Cells. 2023 Mar 25;12(7):1012. doi: 10.3390/cells12071012. PMID: 37048085; PMCID: PMC10093562.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/microglial-activation-and-phenotype-in-air-pollution-neurotoxicity-implications-for-parkinsons-disease/