Objective: To explore the effects of ginsenoside Rb1 on the cognitive impairment of Parkinson’s disease (PD) model.

Background: Memory deficiency is a common non-motor symptom of 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. Whether Rb1 can improve memory deficiency in the PD animal model and the underlying mechanism is still unknown.

Method: We cultured primary hippocampal neuron and used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to construct the mouse model of PD. Morris water maze test was used to examine the effects of Rb1 on the memory deficits. Western blot and immunostaining were used to explore the effects of Rb1 on the α-synuclein expression. Stereotaxic injection of α-synuclein shRNA in the hippocampus to detect the effects of α-synuclein knockdown on the memory function. Long-term potentiation (LTP) and miniature excitatory postsynaptic currents (mEPSCs) were recorded to examine the effects of Rb1 on the synaptic plasticity and glutamatergic transmission.

Results: We found that Rb1 can prevent the spatial learning and memory deficits, increase LTP and the frequency and amplitudes of mEPSCs, suggesting Rb1 improved the hippocampal synaptic plasticity and glutamatergic transmission in the MPTP model. In addition, Rb1 also protected hippocampal neurons from death in the MPTP mouse model. The underlying neuroprotective mechanism of Rb1-improved synaptic plasticity involves Rb1 promoting hippocampal CA3 α-synuclein expression, restoring the glutamate in the CA3-schaffer collateral-CA1 pathway, and sequentially increasing postsynaptic density-95 (PSD-95) expression. We also found that α-synuclein knockdown in the hippocampus induced the memory deficiency in the normal mice. Furthermore, α-synuclein knockdown decreased LTP and PSD-95 expression in the hippocampus.

Conclusion: We provide evidence that Rb1 modulates memory function, synaptic plasticity, and excitatory transmission via the trans-synaptic α-synuclein/PSD-95 pathway. Rb1 may serve as a functional drug in treating the memory deficiency in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/ginsenoside-rb1-prevents-mptp-induced-changes-in-hippocampal-memory-via-regulation-of-the-%ce%b1-synuclein-psd-95-pathway/