Research Paper Volume 11, Issue 14 pp 5008—5034
Ginsenoside Rb1 regulates prefrontal cortical GABAergic transmission in MPTP-treated mice
- 1 Department of Traditional Chinese Medicine, School of Medicine, Xiamen University, Xiamen 361102, China
- 2 Key Laboratory of Neuroscience, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China
- 3 Department of Medical Imaging, The Second Affiliated Hospital, Medical College of Shantou University, Shantou 515041, China
- 4 School of Basic Medical Sciences, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China
- 5 Provincial Key Laboratory of Medical Molecular Imaging, Shantou 515041, China
- 6 Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen 361102, China
- 7 Shenzhen Research Institute of Xiamen University, Shenzhen 518000, China
Received: May 8, 2019 Accepted: July 10, 2019 Published: July 17, 2019
https://doi.org/10.18632/aging.102095How to Cite
Copyright © 2019 Liu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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 GABAARα1 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 GABABR1 to enhance GABA release and GABAA 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.
Abbreviations
CEST: chemical exchange saturation transfer; DA: dopamine; eIPSCs: evoked inhibitory postsynaptic currents; GABA: gamma-aminobutyric acid; mIPSCs: miniature inhibitory postsynaptic currents; MPP+: 1-methyl-4-phenylpyridinium-iodide; MPTP: 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine; PFC: prefrontal cortex; PSD: postsynaptic density.