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P3‐341: Effects of tetrahydroxystilbene glucoside on synapses and alpha‐synuclein in brains of aged mice
Author(s) -
Li Lin,
Sun Funling,
Zhang Ruyi,
Wang Yuqin
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.1565
Subject(s) - morris water navigation task , neuroscience , striatum , hippocampus , hippocampal formation , postsynaptic density , postsynaptic potential , biology , psychology , chemistry , medicine , dopamine , inhibitory postsynaptic potential , excitatory postsynaptic potential , receptor
Background: Synaptic dysfunction and alpha-synuclein play important roles in the progression of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB). 2,3,5,4’-Tetrahydroxystilbene glucoside (TSG) is a main component extracted from Polygonum multiflorum. The aim of this study was to investigate the effects of TSG on synapses and its possible mechanisms in the brain of aged mice for the treatment of age-related neurodegenerative diseases. Methods: TSG (50, 100 and 200mg/kg) or vehicle was intragastrically administered daily to 18month-old C57BL mice for 3 months. The learning and memory ability was detected by Morris water maze test and step-through task. The movement ability was measured by the rotorod, pole test and locomotor activity tests. The synaptic ultrastructure was detected by electron microscopy. The expression of synaptic proteins and phosphorylated CaMKII was measured by immunoblotting. Results: (1) TSG decreased the escape latency in Morris water maze test, and extended latency and reduced error times in step-through task, dementrating that TSG improved the learning and memory ability in aged mice (21 months old). (2) TSG extended the time on rotorod, and shortened the turntime and the down-time when climbing down from the pole, indicating that TSG improved movement function in aged mice. (3) TSG effectively protected synaptic ultrastructure of the hippocampal CA1 area, increased postsynaptic density length in striatum, increased the number of synaptic appositional zone area in hippocampus and striatum, and protected the mitochondrial ultrastructure in aged mice. (4) TSG enhanced the expression of phosphorylated CaMKII, synaptophysin, phosphorylated synapsin I and PSD-95, and reduced the expression of synaptotagmin I in the hippocampus, cortex and striatum of aged mice, consequently improved the synaptic plasticity. (5) TSG inhibited the overexpression and aggregation of alpha-synuclein in the hippocampus, cortex and striatum of aged mice, thus improved the abnormity of alpha-synuclein. Conclusions: TSG improved both learningmemory ability and movement ability in aged mice, through protecting synaptic structure and functions and inhibiting the overexpression and aggregation of alpha-synuclein. The results suggest that TSG may have a promising prospect in treatment of neurodegenerative diseases such as AD, DLB and PDD.