Objective: To delineate the molecular mechanisms involved in bidirectional olfactory-brain-induced neurodegeneration caused by exposure to ambient particulate matter (PM_2.5).

Background: Air pollution has been linked to having detrimental effects on human health. APM_2.5 is one of the major contributors that can penetrate deep inside the systemic circulation, causing oxidative stress and inflammation-associated damage [1]. Inhalational exposure to PM_2.5 in highly polluted regions causes astrocyte and microglia activation due to polyaromatic hydrocarbons (PAHs) instigating neurodegeneration [2]. Our study explores the mechanism of intranasal exposure to PM_2.5 and its bidirectional olfactory-brain-mediated inflammation and neurodegeneration.

Method: Intranasal exposure of PM_2.5 at a dose of 10, 30, and 60µg/ml to C57BL/6 mice for 90 days significantly alters the behavior of mice, as evidenced by olfactory function test and cognitive analysis. These effects were linked to causing impaired spatial memory and motor functions which were assessed by Morris Water Maze (MWM), Novel Object Recognition Test (NORT). Marked changes in the expression of iba-1, GFAP, and CD-68 suggest the glial cells’ increased phagocytotic activity.

Results: Astrocyte and microglial activation in the olfactory bulb of mice after chronic exposure to PM_2.5 leads to significant alterations in the olfactory and cognitive functions. Initiation of the glial cell’s activation and neuroinflammation in the olfactory bulb releases abundant cytokines (IL-1β, IL-18, TNF-α) and inflammatory markers (NF-κB) that further progress neurodegeneration in the brain. Our results correlated with the previous studies and further predicted the molecular mechanism involved in the olfactory-brain-mediated neurodegeneration caused by PM_2.5.

Conclusion: The current study explores the novel molecular mechanisms involved in neurodegeneration through the olfactory-brain axis caused by APM_2.5 exposure. Our results depict the cognitive dysfunction was critically observed at a dose of 60µg/ml for 90 days. Cognitive dysfunction was associated with marked reduction in the movement of mice. Further glial cells activation and ROS mediated neuroinflammation was observed in the olfactory bulb and hippocampus of the mice brain.

References: 1. Lee, S.H., Lin, C.Y., Chen, T.F., Chou, C.C.K., Chiu, M.J., Tee, B.L., Liang, H.J. and Cheng, T.J., 2022. Distinct brain lipid signatures in response to low-level PM2. 5 exposure in a 3xTg-Alzheimer’s disease mouse inhalation model. Science of The Total Environment, p.156456.
2. Li, B., Chang, X., Liang, X., Liu, T., Shen, Y., Zhang, Q., Yang, X., Lyu, Y., Liu, L., Guo, J. and Wu, M., 2023. The role of reactive astrocytes in neurotoxicity induced by ultrafine particulate matter. Science of The Total Environment, p.161416.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/polyaromatic-hydrocarbons-in-ambient-particulate-matter-pm-2-5-mediate-neurodegeneration-through-the-olfactory-brain-axis-in-c57bl-6-mice/