Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam 781101, India.
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam 781101, India; Department of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 15 901, New Haven, CT 06511, USA.
Environ Toxicol Pharmacol. 2023 Aug;101:104183. doi: 10.1016/j.etap.2023.104183. Epub 2023 Jun 13.
Exposure to ambient particulate matter (PM) 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 PM 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 PMinduced 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 PM exposed BEAS2B cells. Further, melatonin treatment at a dose of 50 mg/kg to C57BL/6 mice exposed to PM (at a dose of 60 µg/animal) for 90 days significantly alleviated the neuroinflammation and neurodegeneration caused by PAHs in PM by modulating olfactory-brain and microbiome-gut-brain axis.
暴露于环境细颗粒物（PM）已被证明会扰乱肠道微生物组稳态，并通过肠-脑双向轴引发神经炎症和神经退行性变。多环芳烃（PAHs）是致癌和致突变的，是 PM 的重要有机成分，可能参与微生物组-肠-脑轴介导的神经退行性变。褪黑素（ML）已被证明可调节微生物组并抑制肠道和大脑中的炎症。然而，目前尚无研究报道其对 PM 诱导的神经炎症的影响。在本研究中，观察到 100µM 的 ML 处理可显著抑制由暴露于 PM 的 BEAS2B 细胞产生的条件培养基引起的小胶质细胞活化（HMC-3 细胞）和结肠炎症（CCD-841 细胞）。此外，50mg/kg 剂量的褪黑素处理可显著减轻 60µg/动物 PM 暴露的 C57BL/6 小鼠的神经炎症和神经退行性变，通过调节嗅觉-脑和微生物组-肠-脑轴。
