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Effects of tetrahydroxy-stilbene glucoside on cognitive and motor functions, α-synuclein aggregation and synapse in transgenic mice and in aged mice

Effects of tetrahydroxy-stilbene glucoside on cognitive and ...

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中国神经科学学会第十二届全国学术会议

作者： Lin Li Lan Zhang Ru-yi Zhang Xuanwu Hospital of Capital Medical University Key Laboratory for Neurodegenerative Diseases of Ministry of China Beijing Engineering Research Center for Nerve System Drugs

Objective Aging is the greatest risk factor of senile neurodegenerative diseases such as Alzheimer’s disease（AD）, Parkinson’s disease（PD） and dementia of Lewy body（DLB）. α-Synuclein aggregation is the common pathogenesis of these diseases, and synaptic dysfunction plays an important role in the progression of AD and PD. tetrahydroxy-stilbene glucoside（TSG） is one of the main active component extracted from the root of Polygonum multiflorum. The purpose of this study was to investigate the effects of TSG on the memory and movement functions and its mechanisms related to a-synuclein and synapses in animal models. Methods The memory ability of mice was detected by step-through task and Y maze test. The movement function was measured by the pole test and rotarod test. Transmission electron microscopy was used to observe the synaptic ultrastructure. Western blotting was applied to measure the expression of a-synuclein and synaptic proteins. Results Intragastrical administration of TSG significantly improved the memory and movement functions in α-synuclein transgenic mice and in aged mice. TSG obviously inhibited the overexpression and aggregation of a-synuclein, reduced the expression of phosphorylated α-syn at Ser129, and increased Parkin, Atg5 and LC3 in the multiple brain regions of a-synuclein transgenic mice and aged mice. Moreover, TSG protected the synaptic ultrastructure and increased the number of synaptic connections in the hippocampus and striatum;enhanced the expression of synaptophysin, phosphorylated synapsin I, postsynaptic density protein 95（PSD-95）, and phosphorylated calcium-dependent protein kinase II（p-Ca MK II） in the hippocampus, striatum and cerebral cortex of aged mice. Conclusion TSG improved the memory and movement functions through inhibiting a-synuclein aggregation and protecting synapses in multiple brain regions of a-synuclein transgenic mice and aged mice. The results suggest that TSG may be beneficial to treat AD, PD, PD dementia and DLB.

关键词： tetrahydroxy-stilbene glucoside cognitive function motor function asynuclein synapse neurodegenerative diseases

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