Liu Yan, Zong Xiaodan, Huang Jie, Guan Yanfei, Li Yuanquan, Du Ting, Liu Keyin, Kang Xinpan, Dou Chunyan, Sun Xiangdong, Wu Renhua, Wen Lei, Zhang Yunlong
Department of Traditional Chinese Medicine, School of Medicine, Xiamen University, Xiamen 361102, China.
Key Laboratory of Neuroscience, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China.
Aging (Albany NY). 2019 Jul 17;11(14):5008-5034. doi: 10.18632/aging.102095.
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 GABARα1 and increase its expression in the SH-SY5Y cells and in the prefrontal cortex (PFC) of MPTP model and . Furthermore, Rb1 can promote prefrontal cortical GABA level and GABAergic transmission in MPTP-treated mice. We also revealed that Rb1 may suppress presynaptic GABAR1 to enhance GABA release and GABA 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.
帕金森病（PD）是一种常见的神经退行性疾病，其特征为运动功能障碍以及认知障碍等非运动症状，γ-氨基丁酸（GABA）介导的抑制性传递功能异常在PD发病机制中起重要作用。人参根提取物的主要成分人参皂苷Rb1分子已被证明可改善PD患者的运动功能障碍并预防多巴胺能神经元死亡。然而，Rb1是否能调节PD相关功能障碍中的GABA能传递及其潜在机制仍不清楚。在本研究中，我们探讨了Rb1对1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的PD小鼠模型中GABA能突触传递的影响。我们证明Rb1可与GABARα1结合并增加其在SH-SY5Y细胞和MPTP模型小鼠前额叶皮质（PFC）中的表达。此外，Rb1可提高MPTP处理小鼠前额叶皮质的GABA水平和GABA能传递。我们还发现Rb1可能通过抑制突触前GABAR1来增强GABA释放和GABA受体介导的抑制性传递。此外，Rb1减轻了MPTP诱导的步态动力学功能障碍和认知障碍，这种神经保护机制可能涉及调节前额叶皮质的GABA能传递。因此，Rb1可能是治疗PD的潜在候选药物。
