Ambient particulate matter (PM2.5) exposure contributes to neurodegeneration through the microbiome-gut-brain axis: Therapeutic role of melatonin

Environ Toxicol Pharmacol. 2023 Aug:101:104183. doi: 10.1016/j.etap.2023.104183. Epub 2023 Jun 13.

Abstract

Exposure to ambient particulate matter (PM2.5) has been shown to disturb the gut microbiome homeostasis and cause initiation of neuroinflammation and neurodegeneration via gut-brain bi-directional axis. Polyaromatic hydrocarbons (PAHs), which are carcinogenic and mutagenic, are important organic constituents of PM2.5 that could be involved in the microbiome-gut-brain axis-mediated neurodegeneration. Melatonin (ML) has been shown to modulate the microbiome and curb inflammation in the gut and brain. However, no studies have been reported for its effect on PM2.5-induced neuroinflammation. In the current study, it was observed that treatment with ML at 100 µM significantly inhibits microglial activation (HMC-3 cells) and colonic inflammation (CCD-841 cells) by the conditioned media from PM2.5 exposed BEAS2B cells. Further, melatonin treatment at a dose of 50 mg/kg to C57BL/6 mice exposed to PM2.5 (at a dose of 60 µg/animal) for 90 days significantly alleviated the neuroinflammation and neurodegeneration caused by PAHs in PM2.5 by modulating olfactory-brain and microbiome-gut-brain axis.

Keywords: Air Pollution; Fine Particulate matter; Gut-Brain axis; Hippocampus; Melatonin; Neurodegeneration; Olfactory bulb.

MeSH terms

  • Air Pollutants* / analysis
  • Air Pollutants* / toxicity
  • Animals
  • Brain-Gut Axis
  • Inflammation
  • Melatonin* / pharmacology
  • Melatonin* / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Neuroinflammatory Diseases
  • Particulate Matter / analysis
  • Particulate Matter / toxicity

Substances

  • Particulate Matter
  • Air Pollutants
  • Melatonin