Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhon Pathom, 73170, Thailand; School of Food Technology, Institute of Agricultural Technology, Suranaree University of Technology, Nakhon Ratchasima, 30000, Thailand.
Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhon Pathom, 73170, Thailand; Institute of Pure and Applied Biology, Zoology division, Bahauddin Zakariya University, Multan, 60800, Pakistan.
Food Chem Toxicol. 2020 Dec;146:111829. doi: 10.1016/j.fct.2020.111829. Epub 2020 Oct 29.
Accumulation of aluminium (Al) in the brain is known to be a toxic insult that result in neurodegenerative diseases and melatonin is known to have neuroprotective role. The present study was designed to investigate the neuroprotective effects of melatonin for aluminium chloride (AlCl)-induced neurotoxicity in rats. Twelve-week old male Wistar rats were orally received 175 mg/kg AlCl with or without 5 mg/kg melatonin intraperitoneal pretreatment. Group 3 intraperitoneally recieved 5 mg/kg melatonin and group 4 rats were orally treated with saline solution for 8 weeks. A series of behavioral tests, biochemical analysis and expression of AD-associated proteins in the brain were determined after 7 weeks of all treatments. Our results indicated that AlCl treatment tends to induce memory and cognitive impairment. However, melatonin treatment attenuated amyloid beta (Aβ) (1-42) level by decreasing β-secretase, augmented low-density lipoprotein receptor-related protein 1, and neprilysin protein expression. Moreover, AlCl -induced endoplasmic reticulum (ER) stress and oxidative stress was attenuated by melatonin supplementation. In conclusion, these findings demonstrate a protective role of melatonin against Aβ peptide accumulation, ER stress and oxidative stress in the AlCl -treated AD model. Hence, the melatonin supplement might be an alternative way to alleviate the development of AD.
铝（Al）在大脑中的积累已知是一种毒性损伤，会导致神经退行性疾病，而褪黑素已知具有神经保护作用。本研究旨在探讨褪黑素对氯化铝（AlCl）诱导的大鼠神经毒性的神经保护作用。12 周龄雄性 Wistar 大鼠经口给予 175mg/kg AlCl3，同时或不预先给予 5mg/kg 褪黑素腹腔内给药。第 3 组腹腔内给予 5mg/kg 褪黑素，第 4 组大鼠经口给予生理盐水 8 周。所有治疗 7 周后，进行一系列行为测试、生化分析和大脑中与 AD 相关蛋白的表达。我们的结果表明，AlCl3 处理会导致记忆和认知障碍。然而，褪黑素治疗通过降低β-分泌酶、增加低密度脂蛋白受体相关蛋白 1 和 Neprilysin 蛋白表达来减轻淀粉样β（Aβ）（1-42）水平。此外，褪黑素补充可减轻 AlCl3 诱导的内质网（ER）应激和氧化应激。总之，这些发现表明褪黑素对 AlCl3 处理的 AD 模型中的 Aβ肽积累、ER 应激和氧化应激具有保护作用。因此，褪黑素补充可能是减轻 AD 发展的一种替代方法。
