The Protective Estrogen-like Effect And Mechanism Of Quercetin On Hippocampus Neurons Of Rats

Alzheimer’s disease(AD),also known as senile dementia,is a neurodegenerative disease caused by a variety of factors,Mainly for synapse loss and neuronal apoptosis in the hippocampus and cerebral cortex.So protect hippocampal neurons can delay the occurrence and development of AD.Studies have shown that estrogen closely related to the AD, estrogen can be in several ways to play a protective effect on neurons.Phytoestrogens are called selective estrogen receptor modulators, can enhance the growth and survival of neurons,while avoiding the side effects of estrogen replacement therapy.Quercetin(Que) belongs to flavonoids, is a kind of phytoestrogen. Have certain protection effect of quercetin on neuronal injury caused by cerebral ischemia reperfusion, amyloid beta protein and heavy metals.Primary cultured rat hippocampal neurons was used in the experment.Cells were cultured for 4 to 5 days 17β- estradiol(0.02μmol·L-1), genistein( 2μmol·L-1) and three different concentrations of quercetin(50μmol·L-1,25μmol·L-1, 12.5μmol·L-1) were added for 24/48 hours.The effects of Quercetin on activity of hippocampal neurons were tested by MTT. Effects of quercetin on synaptic morphology of hippocampal neurons were compared by methed of immunohistochemical stain, and the mechanism of quercetin estrogen-like through the use of tools drugs estrogen receptor antagonist ICI182,780, estrogen α receptor antagonist(MPP) and estrogen β receptor antagonist(PHTPP).The results showed that quercetin may increase the activity of hippocampal neurons of rat(P﹤0.05).Effect of quercetin on hippocampal neurons and protection into a dose-dependent increase.25μmol·L-1quercetin has a protective effect in low density of hippocampal neurons(P﹤0.05).When the estrogen receptor antagonist, 50μmol·L-1quercetin can still improve the activity of hippocampal neurons(P ﹤ 0.05),prolonged duration of action of three different concentrations of quercetin may increase the activity of hippocampal neurons(P ﹤ 0.05).Quercetin can increase the number and length of synapses in hippocampal neurons(P﹤0.05),promote synaptogenesis.After completely antagonize estrogen receptor, quercetin is still can improve the number and length of synapses in hippocampal neurons(P﹤0.05).Quercetin can increase the number and length of synapses in hippocampal neurons of estrogen β receptor antagonist. The number and length of synaptic is higher than the estrogen αreceptor antagonist(P ﹤ 0.05).Western blot results showed that quercetin could increase the expression of estrogen alpha receptor protein.Quercetin has a positive effect on the protection and promote synaptogenesi of rat hippocampal neurons.Mechanism for estrogen-like effect of quercetin may play a variety of ways, not only rely on the classical estrogen receptor pathway.Quercetin is mainly rely on estrogen receptor alpha play mediated in estrogen receptor related pathway.