TETRAHYDROXYSTILBENE GLUCOSIDE AMELIORATES MEMORY AND MOVEMENT FUNCTIONS, PROTECTS SYNAPSES AND INHIBITS α-SYNUCLEIN AGGREGATION IN HIPPOCAMPUS AND STRIATUM IN AGED MICE

Abstract

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). Synaptic dysfunction plays an important role in the progression of cognitive impairment and movement disorder among these neurodegenerative diseases. Synaptic degeneration occurs early in the progression of AD involving neocortical and limbic system circuitries. Accumulating oligomeric α-synuclein may mediate early synaptic pathology in PD and DLB by disrupting synaptic vesicles. Polygonum multiflorum has been widely used in China as an anti-aging agent since ancient times. 2,3,5,4’-Tetrahydroxystilbene-2-O-β-D-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 synapses and a-synuclein in aged mice. The memory ability of mice was detected by step-through passive avoidance task. 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 synapse-related proteins and a-synuclein. Intragastrical administration of TSG for 3 months significantly improved the memory and movement functions in aged mice. TSG treatment obviously protected the synaptic ultrastructure and increased the number of synaptic connections in the hippocampal CA1 region and striatum; enhanced the expression of synaptophysin, phosphorylated synapsin I and postsynaptic density protein 95 (PSD-95), elevated phosphorylated calcium/calmodulin-dependent protein kinase II (p-CaMK II) expression, and inhibited the overexpression and aggregation of a-synuclein in the hippocampus, striatum and cerebral cortex of aged mice. TSG improved the memory and movement functions in aged mice through protecting synapses and inhibiting a-synuclein overexpression and aggregation in multiple brain regions. The results suggest that TSG may have the potential to treat Alzheimer's disease, Parkinson's disease dementia and dementia of Lewy body.