Objectives: Estrogen replacement therapy (ERT) reduces the risk of Alzheimer's disease and symptoms in postmenopausal and elderly women. However, ERT is associated with increased risk of uterine and breast cancer. Dietary phytoestrogens have been suggested as a potential alternative to ERT, while little information is available regarding the effects and the underlying mechanisms of such treatment on central neuron function. The present study aimed to determine the effects of phytoestrogens including genistein and daidzein on the proliferation and survival of the hippocampus neural cells, which are of importance in learning and memory function.
Measurements: H19-7/IGF-IR neural cell line was cultured in DMEM absented of serum for 72 h, and treated with various concentrations of genistein, daidzein or 17β-estradiol. Neuronal cell viability and proliferation were determined by MTT and BrdU assay, respectively Cell cycle analysis was performed using flow cytometry. The effects of genistein and daidzein on brain-derived neurotrophic factor (BDNF) mRNA and protein expression were determined by RT-PCR and ELISA, respectively. The effect of Trk receptors inhibitor on genistein and daidzein - induced hippocampus neuronal cell proliferation was also examined.
Results: 17β-estradiol, genistein and daidzein ranged from 20 nM to 2000 nM significantly promoted hippocampus neuronal cell viability and proliferation. Similar to the effect of 17β-estradiol, genistein and daidzein induced an increase in the percentage of cells in S phase. Genistein and daidzein significantly increased the expression of BDNF mRNA and protein levels. The effect of genistien and daidzein on hippocampus neuronal proliferation was blocked by K252a, a selective Trk receptors inhibitor.
Conclusion: This study concluded that genistein and daidzein improved hippocampus neuronal cell viability and proliferation in vitro. These neuroprotective effects might be mediated by BDNF-Trk pathway.