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

[Speaker] Lin Li:1,2,3
[Co-author] Lan Zhang:1,2,3, Ru-Yi Zhang:1,2,3
1:Department of Pharmacology, Xuanwu Hospital of Capital Medical University, China, 2:Key Laboratory for Neurodegenerative Diseases of Ministry, China, 3:Beijing Engineering Research Center for Nerve System Drugs, China

Background: 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). Alpha-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 alpha-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 alpha-synuclein and synaptic proteins.
Results: Intragastrical administration of TSG significantly improved the memory and movement functions in alpha-synuclein transgenic mice and in aged mice. TSG obviously inhibited the overexpression and aggregation of alpha-synuclein, reduced the expression of phosphorylated alpha-synuclein at Ser129, and increased Parkin, Atg5 and LC3 in the multiple brain regions of alpha-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-CaMK II) in the hippocampus, striatum and cerebral cortex of aged mice.
Conclusions: TSG improved the memory and movement functions through inhibiting alpha-synuclein aggregation and protecting synapses in multiple brain regions of alpha-synuclein transgenic mice and aged mice. The results suggest that TSG may be beneficial to treat AD, PD, PD dementia and DLB.

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