Tetrahydroxystilbene glucoside ameliorates memory and movement functions, protects synapses and inhibits α-synuclein aggregation in hippocampus and striatum in aged mice.

ABSTRACT

PURPOSE: To investigate the effects of 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) on the memory and movement functions and its mechanisms related to synapses and α-synuclein in aged mice. METHODS: 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 α-synuclein. RESULTS: 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 (PSD95), elevated phosphorylated calcium/calmodulin-dependent protein kinase II (p-CaMKII) expression, and inhibited the overexpression and aggregation of α-synuclein in the hippocampus, striatum and cerebral cortex of aged mice. CONCLUSION: TSG improved the memory and movement functions in aged mice through protecting synapses and inhibiting α-synuclein overexpression and aggregation in multiple brain regions. The results suggest that TSG may be beneficial to the treatment of ageing-related neurodegenerative diseases.