There is an abundance of evidence showing that repeated use of 3,4-methlylenedioxymethamphetamine (MDMA; ecstasy) is associated with brain dysfunction, memory disturbance, locomotor hyperactivity, and hyperthermia. MDMA is toxic to both the serotonergic neurons and dopaminergic system. Adenosine is an endogenous purine nucleoside with a neuromodulatory function in the central nervous system. Nuclear factor kappa-B (NF-kB) plays a pivotal role in the initiation and perpetuation of an immune response by triggering the expression of major inflammatory mediators such as cytokines, chemokines, and adhesion molecules. Here, we investigated the effects of the A2a adenosine receptor (A2a-R) agonist (CGS) and antagonist (SCH) on NF-kB expression after MDMA administration. Male Sprague-Dawley rats were injected to MDMA (10 mg/kg) followed by intraperitoneal injection of either CGS or SCH (0.03 mg/kg each) to animals. The hippocampi were then removed for western blot and RT- PCR analyses. MDMA significantly elevated NF-kB expression. Our results show that administration of CGS following MDMA significantly elevated the NF-kB expression both at mRNA and protein levels. By contrast, administration of the A2a-R antagonist SCH resulted in a decrease in the NF-kB levels. Taken together, these results indicate that, co-administration of A2a agonist (CGS) can protect against MDMA neurotoxic effects by increasing NF-kB expression levels; suggesting a potential application for protection against the neurotoxic effects observed in MDMA users.

译文

有大量证据表明,重复使用3,4-甲基二氧基甲基苯丙胺 (MDMA; 摇头丸) 与脑功能障碍,记忆障碍,运动亢进和体温过高有关。MDMA对血清素能神经元和多巴胺能系统均有毒。腺苷是一种内源性嘌呤核苷,在中枢神经系统中具有神经调节功能。核因子kappa-B (NF-kB) 通过触发主要炎症介质 (例如细胞因子,趋化因子和粘附分子) 的表达,在免疫反应的启动和持续中起关键作用。在这里,我们研究了MDMA给药后A2a腺苷受体 (A2a-R) 激动剂 (CGS) 和拮抗剂 (SCH) 对NF-kB表达的影响。将雄性Sprague-Dawley大鼠注射至MDMA (10 mg/kg),然后向动物腹膜内注射CGS或SCH (各0.03 mg/kg)。然后去除海马进行蛋白质印迹和rt-pcr分析。MDMA显著升高NF-kB表达。我们的结果表明,在MDMA之后给予CGS显着提高了mRNA和蛋白质水平的NF-kB表达。相比之下,施用A2a-R拮抗剂SCH导致NF-kB水平降低。总之,这些结果表明,A2a激动剂 (CGS) 的共同给药可以通过增加NF-kB表达水平来预防MDMA神经毒性作用; 提示潜在的应用,以防止在MDMA使用者中观察到的神经毒性作用。

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