Department of Medical Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
Department of Neurology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Mol Biol Rep. 2024 May 25;51(1):690. doi: 10.1007/s11033-024-09631-1.
Methamphetamine (METH) is an addictive psychostimulant with deleterious effects on the central nervous system. Chronic use of METH in high doses impairs cognition, attention and executive functions, but the underlying mechanisms are still unclear. Sirtuin 1 (SIRT1) is a post-translational regulator that is downregulated following METH neurotoxicity. Melatonin is a neuroprotective hormone that enhances mitochondrial metabolism. Here, we evaluated the effect of melatonin on METH-induced attention deficits disorder and the involvement of the miR-181/SIRT1 axis in melatonin neuroprotection.
METH at a dose of 5 mg/kg was injected for 21 consecutive days. The animals were assigned to receive either melatonin or the vehicle after METH injections. Attention levels were evaluated with abject-based attention test. In the prefrontal cortex, the expression levels of miR-181a-5p, SIRT1, p53 and CCAR2, as well as the mtDNA copy numbers were evaluated using qRT-PCR and western blotting. The outcomes revealed that melatonin treatment following METH injections improved METH-induced attention deficits. METH toxicity can be associated with changes in the miR-181/SIRT1 axis, elevated levels of p53 and COXII, and decreased levels of mtDNA in the prefrontal cortex of adult rats. Interestingly, administration of melatonin can improve the expression of these molecules and reduces the toxic effects of METH.
Melatonin ameliorated the neurotoxicity of METH in the prefrontal cortex and the miR-181/SIRT1 axis is involve in the protective effects of melatonin. However, melatonin can be potentially administrated to improve attention impairment in METH use disorders.
甲基苯丙胺（METH）是一种成瘾性的精神兴奋剂，对中枢神经系统有有害影响。慢性大剂量使用 METH 会损害认知、注意力和执行功能，但潜在机制尚不清楚。沉默调节蛋白 1（SIRT1）是一种翻译后调节物，在 METH 神经毒性后下调。褪黑素是一种神经保护激素，可增强线粒体代谢。在这里，我们评估了褪黑素对 METH 诱导的注意力缺陷障碍的影响，以及 miR-181/SIRT1 轴在褪黑素神经保护中的作用。
METH 以 5mg/kg 的剂量连续注射 21 天。动物在 METH 注射后被分配接受褪黑素或载体。使用基于物体的注意力测试评估注意力水平。在大脑前额叶皮层中，使用 qRT-PCR 和 Western blot 评估 miR-181a-5p、SIRT1、p53 和 CCAR2 的表达水平以及 mtDNA 拷贝数。结果表明，METH 注射后给予褪黑素可改善 METH 诱导的注意力缺陷。METH 毒性可能与 miR-181/SIRT1 轴的改变、p53 和 COXII 水平升高以及成年大鼠前额叶皮层中线粒体 DNA 水平降低有关。有趣的是，褪黑素的给药可以改善这些分子的表达，并减轻 METH 的毒性作用。
褪黑素改善了 METH 在前额叶皮层中的神经毒性，miR-181/SIRT1 轴参与了褪黑素的保护作用。然而，褪黑素可能可以被潜在地用于改善 METH 使用障碍中的注意力损伤。
