Objective: To explore the therapeutic potential of melatonin in attenuating the PM_2.5 induced inflammation and neurodegeneration through the Gut-brain axis in C57BL/6 mice.

Background: The intestinal microbiome influences brain development, modulates behavior, and contributes to neurodegeneration during inflammatory conditions. Air pollution has been linked to causing detrimental health concerns, causing respiratory, cardiovascular diseases, and a potent environmental risk factor for causing neurodegeneration. However, the plausible mechanism mediating neurodegeneration through the Gut-Brain axis or olfactory bulb is still unclear.

Method: PM_2.5 intranasal exposure at a dose of 60µg/ml causes glial cells activation in the olfactory bulb, leading to neuroinflammation and glial cells activation in the brain. Motor damage and spatial memory were assessed by Open Field Test (OFT), Novel Object Recognition Test (NORT), and Morris Water Maze (MWM). Polyaromatic hydrocarbons were found to be the major contributing factor in causing bidirectional inflammation and neurodegeneration. Similarly, neuroimaging of the brain revealed marked changes in the percentage vascularity of the brain along with altered neurotransmitter levels was observed in the intestine and hippocampus tissues of C57BL/6 mice (n=10).

Results: Increased expression of GFAP, iba-1, and CD-68 markers were observed in the mice’s olfactory bulb and hippocampal regions along with increased IL-1β expression in the colon. Decreased levels of neurotransmitters indicate chronic bidirectional inflammation in the intestinal microbiome and the brain causing hippocampal memory loss as observed from the neurobehavioral analysis [Open Field Test (OFT), Novel Object Recognition Test (NORT), and Morris Water Maze (MWM)]. Further, melatonin treatment at a dose of 50mg/kg was found to attenuate the PM_2.5 mediated inflammation and neurodegeneration in the olfactory bulb, intestine, and brain.

Conclusion: The present study confirms the neurotoxic effect of APM_2.5 at a dose of 60µg/ml through affecting the intestinal microbiome and the olfactory route. Melatonin was found to alleviate the PM_2.5 induced ROS and inflammation along with showing signs of enhanced memory and attenuating motor impairment in C57BL/6 mice.

References: [1] Fouladi, F., Bailey, M.J., Patterson, W.B., Sioda, M., Blakley, I.C., Fodor, A.A., Jones, R.B., Chen, Z., Kim, J.S., Lurmann, F. and Martino, C., 2020. Air pollution exposure is associated with the gut microbiome as revealed by shotgun metagenomic sequencing. Environment international, 138, p.105604.
[2] Costa, L.G., Cole, T.B., Coburn, J., Chang, Y.C., Dao, K. and Roqué, P.J., 2017. Neurotoxicity of traffic-related air pollution. Neurotoxicology, 59, pp.133-139.
[3] Calderón-Garcidueñas, L., Solt, A.C., Henríquez-Roldán, C., Torres-Jardón, R., Nuse, B., Herritt, L., Villarreal-Calderón, R., Osnaya, N., Stone, I., García, R. and Brooks, D.M., 2008. Long-term air pollution exposure is associated with neuroinflammation, an altered innate immune response, disruption of the blood-brain barrier, ultrafine particulate deposition, and accumulation of amyloid β-42 and α-synuclein in children and young adults. Toxicologic pathology, 36(2), pp.289-310.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/melatonin-attenuates-the-bidirectional-gut-brain-axis-mediated-inflammation-caused-by-ambient-particulate-matter-pm2-5-and-averts-neurodegeneration/