饱和脂肪酸对胚胎神经系统发育的影响及机制研究

项目名称： 饱和脂肪酸对胚胎神经系统发育的影响及机制研究

项目编号： No.81200879

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 王贞

作者单位： 山东大学

项目金额： 23万元

中文摘要： 孕期肥胖可引起子代神经系统发育异常，其发生机理至今尚不清楚。肥胖患者常伴有游离脂肪酸水平长期升高，其中饱和脂肪酸（SFAs）与神经系统功能损伤密切相关。我们在预实验中发现，高SFAs饮食性肥胖孕鼠组的胚鼠神经干细胞（NSCs）增殖明显低于正常饮食组。另外，SFAs引起原代培养的小鼠胚胎NSCs增殖分化异常，并下调Notch1 mRNA的表达。上述结果提示，SFAs可能是通过Notch信号通路调控NSCs的增殖分化，进而导致胚胎神经系统发育异常。为验证该假设，拟建立高SFAs饮食性肥胖动物模型，系统研究SFAs对胎鼠神经系统发育的影响；利用免疫荧光、蛋白印迹等方法检测SFAs对在体及离体NSCs增殖、分化的影响；利用基因转染、小干扰RNA等方法，检测Notch信号通路在SFAs调节NSCs增殖分化中的作用。通过上述研究，可为深入理解孕期肥胖致胚胎神经损伤的发病机理和治疗提供理论依据。

中文关键词： 饱和脂肪酸；神经干细胞；增殖；分化；

英文摘要： Previous studies have suggested that pregnancy obesity may alter brain structure in the offspring. However, the underlying mechanism is still unclear. Obesity is often marked by elevated free fatty acid levels, especially saturated fatty acids (SFAs), which play an important role in brain injury. Our preliminary data showed that, the proliferation of neural stem cells (NSCs) was decreased in fetuses from mothers fed the high SFAs diet when compared to controls. Furthermore, along with the abnormal proliferation and differentiation of the mouse embryonic NSCs in vitro, the level of Notch1 mRNA was also downregulated after SFAs treatment. These data suggested that SFAs played a role in neurogenesis through Notch passway and affected the development of embryonic nervous system. To verify the hypothesis, further studies should be carried out to investigate the effects of SFAs on the development of embryonic nervous system using high SFAs diet-induced pregnancy obesity modle; the effects of SFAs on the proliferation and differentiation of NSCs in vivo and in vitro; the role of Notch pathway in the effects of SFAs on neurogenesis using gene transfection and small interfering RNA. The study may further understanding of the mechanism of the negative effect of pregnancy obesity on the development of embryonic nervous sys

英文关键词： saturated fatty acids；neural stem cells；proliferation；differentiation；