Ginsenoside Rb1 regulates prefrontal cortical GABAergic transmission in MPTP-treated mice
Ginsenoside Rb1 regulates prefrontal cortical GABAergic transmission in MPTP-treated mice
复制标题
人参皂苷 Rb1 调节 MPTP 处理小鼠的前额皮质 GABA 能传递
DOI：
10.18632/aging.102095
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发表时间：
2019-07-31
期刊：
影响因子：
5.2
通讯作者：
Zhang, Yunlong
中科院分区：
文献类型：
--
作者：
Liu, Yan;Zong, Xiaodan;Zhang, Yunlong
帕金森病（Parkinson's disease，PD）是一种常见的神经退行性疾病，以运动功能障碍和认知功能障碍等非运动症状为特征，γ-氨基丁酸（gamma-aminobutyric acid，GABA）介导的抑制性传递功能障碍在PD发病中起重要作用。人参根提取物的主要成分人参皂苷Rb 1分子已被证明可以改善PD中的运动缺陷并防止多巴胺能神经元死亡。然而，Rb 1是否可以调节PD相关缺陷中的GABA能传递及其潜在机制仍不清楚。本研究在1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）帕金森病（PD）小鼠模型上，探讨Rb 1对GABA能突触传递的影响。本实验在体外和体内研究中证实Rb 1可与GABA（A）R α 1结合，并在MPTP模型的SH-SY 5 Y细胞和前额叶皮层（PFC）中增加其表达。Rb_1还能促进MPTP处理小鼠前额叶皮层GABA水平和GABA能传递。Rb 1可能通过抑制突触前GABA（B）R1而增强GABA的释放和GABA（A）受体介导的抑制性传递。此外，Rb 1减轻MPTP诱导的步态动力学和认知功能障碍，这种神经保护机制可能涉及调节前额叶皮层GABA能传递。因此，Rb 1可作为治疗PD的潜在候选药物。
Parkinson's disease (PD) is a common neurodegenerative disease, featured by motor deficits and non-motor symptoms such as cognitive impairment, and malfunction of gamma-aminobutyric acid (GABA) mediated inhibitory transmission plays an important role in PD pathogenesis. The ginsenoside Rb1 molecule, a major constituent of the extract from the Ginseng root, has been demonstrated to ameliorate motor deficits and prevent dopaminergic neuron death in PD. However, whether Rb1 can regulate GABAergic transmission in PD-associated deficits and its underlying mechanisms are still unclear. In this study, we explored the effects of Rb1 on the GABAergic synaptic transmission in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. We demonstrated that Rb1 can bind with GABA(A)R alpha 1 and increase its expression in the SH-SY5Y cells and in the prefrontal cortex (PFC) of MPTP model in vitro and in vivo. Furthermore, Rb1 can promote prefrontal cortical GABA level and GABAergic transmission in MPTP-treated mice. We also revealed that Rb1 may suppress presynaptic GABA(B)R1 to enhance GABA release and GABA(A) receptor-mediated inhibitory transmission. In addition, Rb1 attenuated MPTP-induced dysfunctional gait dynamic and cognitive impairment, and this neuroprotective mechanism possibly involved regulating prefrontal cortical GABAergic transmission. Thus, Rb1 may serve as a potential drug candidate for the treatment of PD.