Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
Neurotox Res. 2014 Apr;25(3):286-94. doi: 10.1007/s12640-013-9419-y. Epub 2013 Aug 23.
Methamphetamine (METH) is a highly addictive drug causing neurodegenerative diseases. METH has been known to be neurotoxic by inducing oxidative stress, free radical, and pro-inflammatory cytokines. Previous studies have shown that METH could induce neuron and glial cell death, especially inducing glial cell-mediated neurotoxicity that plays a critical role in stress-induced central nervous system damage. Therefore, the aim of the present study is to explore the mechanisms of METH-induced cell death in the glial cell. METH-induced glial cells death is mediated via mitochondrial damage pathway. METH activates the upregulation of the Bax, cytochrome c, cleavage caspase 9 and 3 proteins, and downregulation of Bcl-XL protein in cascade. Pretreatment with melatonin, a neurohormone secreted by the pineal gland, effectively reduced glial cell death. Moreover, melatonin increased the Bcl-XL/Bax ratio but reduced the level of cytochrome c, cleavage caspase 9 and 3 proteins. Therefore, these results demonstrated that melatonin could reduce the cytotoxic effect of METH by decreasing the mitochondrial death pathway activation in glial cells. This outcome suggests that melatonin might be beneficial as the neuroprotection in neurodegenerative diseases caused by METH or other pathogens.
甲基苯丙胺（METH）是一种高度成瘾的毒品，可导致神经退行性疾病。已知 METH 通过诱导氧化应激、自由基和促炎细胞因子而具有神经毒性。先前的研究表明，METH 可诱导神经元和神经胶质细胞死亡，特别是诱导神经胶质细胞介导的神经毒性，这在应激诱导的中枢神经系统损伤中起着关键作用。因此，本研究旨在探讨 METH 诱导神经胶质细胞死亡的机制。METH 诱导的神经胶质细胞死亡是通过线粒体损伤途径介导的。METH 激活 Bax、细胞色素 c、裂解 caspase 9 和 3 蛋白的上调，并级联地下调 Bcl-XL 蛋白。预先用褪黑素处理，褪黑素是松果腺分泌的一种神经激素，可有效减少神经胶质细胞死亡。此外，褪黑素增加了 Bcl-XL/Bax 比值，但降低了细胞色素 c、裂解 caspase 9 和 3 蛋白的水平。因此，这些结果表明褪黑素通过减少神经胶质细胞中线粒体死亡途径的激活，可降低 METH 的细胞毒性作用。这一结果表明，褪黑素可能对由 METH 或其他病原体引起的神经退行性疾病具有神经保护作用。
