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,反复使用3,4-亚甲基二氧基甲基苯丙胺(MDMA;摇头丸)与脑功能障碍,记忆障碍,运动过度活跃和体温过高有关。 MDMA对血清素能神经元和多巴胺能系统均具有毒性。腺苷是在中枢神经系统中具有神经调节功能的内源性嘌呤核苷。核因子κB(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久中起关键作用。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(每只0.03 mg / kg)。然后取出海马,进行western blot和RT-PCR分析。 MDMA显着提高了NF-kB的表达。我们的结果表明,在MDMA之后施用CGS可以显着提高mRNA和蛋白水平上的NF-kB表达。相反,施用A2a-R拮抗剂SCH导致NF-kB水平降低。综上所述,这些结果表明,共同使用A2a激动剂(CGS)可以通过增加NF-kB表达水平来预防MDMA神经毒性作用。提示了针对MDMA用户观察到的抗神经毒性作用的潜在应用。

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