Ginsenoside Rb1 regulates prefrontal cortical GABAergic transmission in MPTP-treated mice

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 GABA A Rα1 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.

Chinese Herbal Medicine Interventions in Neurological Disorder Therapeutics by Regulating Glutamate Signaling

“…Hence, further systemic and large-scale RCTs on these natural constituents are required. Intriguingly, since our series of studies reported the neuroprotective of ginsenoside Rb1 in the PD mouse model recently [ 82 - 84 ], we have started multicenter, randomized, and double-blind clinical trials on Rb1 in patients with PD in China. We hope to provide insights for…”

“…The contradictory results may be due to the cellular model and the time point of glutamate addition. Moreover, Rb1 may also regulate the synaptic glutamate system via the α-synuclein and GABA system in PD [ 83 , 84 ]. Ginsenoside Rb1, together with Rc and Rg5, has also been shown to protect primary medium spiny striatal neurons from glutamate-induced intracellular Ca 2+ concentrations and glutamate-induced apoptosis [ 85 ].…”

“…Recently, we, along with other groups, indicated that ginsenoside Rb1 protects neurons from glutamate-induced excitotoxicity, and shows benefits in PD mouse models [ 82 - 84 ]. However, only a few clinical trials of Rb1 have been reported.…”

Modified Huang-Lian-Jie-Du Decoction Ameliorates Aβ Synaptotoxicity in a Murine Model of Alzheimer’s Disease

“…As stated previously [31], prepared samples were subjected to gel electrophoresis (12% SDS-PAGE) and probed using relevant antibodies. Peroxidase activity was examined by enhanced chemiluminescence (Millipore, MA, USA), and chemiluminescent immunoreactive complexes were collected using the Tanon imaging system (Shanghai, China).…”

Dopaminergic and Metabolic Correlations With Cognitive Domains in Non-demented Parkinson’s Disease

“…In an animal study, Kucinski et al reported that dual dopaminergic-cholinergic lesions in rats induced greater attention deficits than those with only dopaminergic or cholinergic lesions. Another animal study supported the link between the promoted prefrontal cortical GABA level and GABAergic transmission and the amelioration of working memory deficits ( Liu et al, 2019 ). However, how neurotransmitters interact with each other is not well understood.…”