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The Effects of Various Estrogen Doses on the Proliferation and Differentiation of Cultured Neural Stem Cells

Lixia Zhang, Yulong Ma, Pei Qin, Youliang Deng, Zengli Zhang, Yushu Hou, Huadong Zhao, Haili Tang, Zijun Gao and Wugang Hou

The neuroprotective effects of estrogen in neurodegenerative diseases, such as Alzheimer’s disease, cerebral ischemia and Parkinson’s disease, are well documented and involve stimulating neurogenesis. However, the dosage and timing of estrogen treatment is controversial, and the underlying mechanism remains unclear. In this study, we tested the effects of various estrogen doses on the proliferation and differentiation of NSCs. First, we identified estrogen receptor α, β and GPR30 were highly expressed in NSCs. The results from a cell cycle analysis detected by flow cytometry revealed that 10 nM 17β-estradiol (E2) treatments for 3 days significantly increased the proliferation of neural stem cells (NSCs) and the expression level of p-ERK1/2, whereas 50 nM E2 exposures markedly decreased the proliferation of NSCs and the expression level of p-ERK1/2. According to immunofluorescence staining and Western blot analyses, 10 nM E2 treatment for 7 days stimulated NSCs to differentiate into neurons and inhibited their differentiation into astrocytes. These results demonstrate NSCs is definitely the target of estrogen and that an appropriate dose of E2 (10 nM) can significantly increase the proliferation of NSCs and significantly stimulate NSCs to differentiate into neurons, which supports the neuroprotective role of estrogen in neurodegenerative diseases.