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Ginsenoside Rb1 Prevents MPTP-Induced Changes in Hippocampal Memory via Regulation of the α-Synuclein/PSD-95 Pathway

52 Pages Posted: 30 Oct 2018

See all articles by Yunlong Zhang

Yunlong Zhang

Guangzhou Medical University

Xingjun Meng

Southern Medical University

Yan Liu

Xiamen University - School of Medicine

Xiuping Zhang

Xiamen University

Shaogang Qu

Southern Medical University - Central Laboratory and Department of Neurology

More...

Abstract

Memory deficiency is a common non-motor symptom of Parkinson's disease (PD), and conventionally, α-synuclein is considered to be an important biomarker for both motor and cognitive characteristics attributed to PD. However, the role of physiological α-synuclein in cognitive impairment remains undetermined. Ginsenoside Rb1 has been shown to protect dopaminergic neurons (DA) from death and inhibit α-synuclein fibrillation and toxicity in vitro. Our recent study also revealed that ginsenoside Rb1 ameliorates motor deficits and prevents DA neuron death via upregulating glutamate transporter GLT-1 in the 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Whether Rb1 can improve memory deficiency and the underlying mechanism is still unknown. In this study, we found that Rb1 can prevent the spatial learning and memory deficits, increase long-term potentiation (LTP) and hippocampal glutamatergic transmission, and protect hippocampal neurons from death in the MPTP mouse model. The underlying neuroprotective mechanism involves Rb1 improving hippocampal CA3 α-synuclein expression, restoring the glutamate in the CA3-schaffer collateral-CA1 pathway, and sequentially increasing postsynaptic density-95 (PSD-95) expression. Thus, we provide evidence that Rb1 modulates memory function, synaptic plasticity, and excitatory transmission via the trans-synaptic α-synuclein/PSD-95 pathway. Our findings suggest that Rb1 may serve as a functional drug in treating the memory deficiency in PD.

Funding Statement: This project was supported by the National Natural Science Foundation of China (Nos. 81870991 and U1603281 to SQ, No. 81704130 to YZ), the Natural Science Foundation of Fujian Province of China (No. 2017J05139 to YZ), the Natural Science Foundation of Guangdong Province of China (No. 2017A030310643 to YZ), and the China Postdoctoral Science Foundation (No. 2016M590598 to YZ).

Declaration of Interests: The authors declare no conflicts of interest.

Ethics Approval Statement: All experiments were conducted according to the National Institute of Health guidelines on the care and use of animals (NIH Publications No. 8023, revised 1978) and approved by the Institutional Animal Care and Use Committee of Guangzhou Medical University.

Keywords: Parkinson's Disease; Ginsenoside Rb1; Memory Deficits; α-Synuclein; Synaptic Plasticity

Suggested Citation

Zhang, Yunlong and Meng, Xingjun and Liu, Yan and Zhang, Xiuping and Qu, Shaogang, Ginsenoside Rb1 Prevents MPTP-Induced Changes in Hippocampal Memory via Regulation of the α-Synuclein/PSD-95 Pathway (October 25, 2018). Available at SSRN: https://ssrn.com/abstract=3273163 or http://dx.doi.org/10.2139/ssrn.3273163

Yunlong Zhang

Guangzhou Medical University

195 Dongfeng W Rd
Yuexiu Qu
Guangzhou Shi, Guangdong Sheng 510080
China

Xingjun Meng

Southern Medical University

Guangzhou, Guangdong Province
China

Yan Liu

Xiamen University - School of Medicine

Xiamen, Fujian 361005
China

Xiuping Zhang

Xiamen University

Xiamen, Fujian 361005
China

Shaogang Qu (Contact Author)

Southern Medical University - Central Laboratory and Department of Neurology ( email )

Foshan, 528300
China

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