Mental Health Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
Neural Regen Res. 2012 Apr 25;7(12):955-9. doi: 10.3969/j.issn.1673-5374.2012.12.013.
The p75 neurotrophin receptor, which is a member of the tumor necrosis factor receptor superfamily, facilitates apoptosis during development and following central nervous system injury. Previous studies have shown that programmed cell death is likely involved in the neurotoxic effects of 3, 4-methylenedioxy-N-methylamphetamine (MDMA), because MDMA induces apoptosis of immortalized neurons through regulation of proteins belonging to the Bcl-2 family. In the present study, intraperitoneal injection of different doses of MDMA (20, 50, and 100 mg/kg) induced significant behavioral changes, such as increased excitability, increased activity, and irritability in rats. Moreover, changes exhibited dose-dependent adaptation. Following MDMA injection in rat brain tissue, the number of apoptotic cells dose-dependently increased and p75 neurotrophin receptor expression significantly increased in the prefrontal cortex, cerebellum, and hippocampus. These findings confirmed that MDMA induced neuronal apoptosis, and results suggested that this effect was related by upregulated protein expression of the p75 neurotrophin receptor.
p75 神经营养因子受体是肿瘤坏死因子受体超家族的成员，它在发育过程中和中枢神经系统损伤后促进细胞凋亡。先前的研究表明，程序性细胞死亡可能参与了 3,4-亚甲基二氧甲基苯丙胺（MDMA）的神经毒性作用，因为 MDMA 通过调节属于 Bcl-2 家族的蛋白质诱导永生化神经元凋亡。在本研究中，腹腔注射不同剂量的 MDMA（20、50 和 100mg/kg）可诱导大鼠出现明显的行为改变，如兴奋性增加、活动增加和易怒。此外，改变表现出剂量依赖性适应。在大鼠脑组织中注射 MDMA 后，前脑皮质、小脑和海马中的凋亡细胞数量呈剂量依赖性增加，p75 神经营养因子受体表达显著增加。这些发现证实 MDMA 诱导神经元凋亡，结果表明这种效应与 p75 神经营养因子受体的上调蛋白表达有关。
