Estrogen-like Effects And The Mechanism Of Quercetin On Cortical Neurons Of Newborn Rat

Alzheimer’s disease(AD) is a neurodegenerative disease of the central nervous system, which is characterized by deposition of amyloid beta(Aβ) and neurofibrillary tangles and the incidence of women significantly higher than men. The studies have shown that the occurrence and development of AD are closely associated with the declining estrogen levels. Recent researches have revealed that estrogen replacement therapy(ERT) could delay the progression of AD in some extent, but long term use of estrogen will increase the incidence of endometrial cancer and the other diseases, so it’s limited the application of estrogen greatly. The researches have shown that the phytoestrogen which is similar to the chemical structure of estrogen, it’s not only have estrogen-like neuroprotective effects, but also can avoid the adverse reaction, when is used for the age-related diseases, therefore phytoestrogen is expected to replace estrogen for the prevention and treatment of AD. Quercetin, a natural flavonoid compounds, which is very similar to chemical structure of estrogen, is a kind of phytoestrogen. It exerts numerous beneficial effects on nerve, including anti-oxidation, anti-inflammatory and so on. In our previous studies have found that quercetin could promote the proliferation of MCF-7 cells by estrogen receptor α, which is showed the estrogen-like effect.In this research, we investigated the effect of quercetin on primary cultured newborn rat cortex neuron cells which were estrogen depleted, and discussed the possible mechanism, to provide new ideas and strategies for developing a drug of neurodegenerative disease. In this study, MTT was used to determine the effective concentration of quercetin on the protective effects of primary cultured newborn rat cortex neuron cell which is estrogen depletion; Using immunofluorescence cytochemistry technology to observe the effect of quercetin on morphology of cortical neurons; By Western blot detection the expression of estrogen receptors alpha and beta in cortical neurons; and the estrogen receptor antagonist(ICI182,780) was used as a tool to evaluate the relationship between estrogen-like effects of quercetin and estrogen receptor(ER). The results showed that the Que(50,100μmol·L-1) group compared with the control group could significantly improve the activity of the cortical neurons(P < 0.05); The cortical neurons which is cultured for sixth days was identified by immunofluorescence cytochemistry with Neuronal Class Ⅲβ-Tubulin(Tuj1) antibody, the results showed that the antibody staining was positive, and the Que(50,100μmol·L-1) group significantly promoted the formation of synapse, most of the neurons were full, and the synapses of neurons became thick、growth, and connect to a dense neural network; And Que(50,100μmol·L-1) group could obviously increase the expression of estrogen receptor alpha protein, in addition, the neural protective effect of quercetin can be inhibited by ICI182,780. The above experimental results validated that the quercetin had estrogen-like effect and played a protective role on cultured cortex neuron in vitro, aslo confirmed that the quercetin mainly by combinate with estrogen receptor alpha exert estrogen-like protection through ICI182,780.