Wang Zhen, Liu Dexiang, Zhang Qun, Wang Jianmei, Zhan Jingmin, Xian Xiuying, Du Zhaoxia, Wang Xueer, Hao Aijun
Department of Physiology, Shandong University School of Medicine, Shandong, People's Republic of China; Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong, People's Republic of China.
J Neurosci Res. 2014 May;92(5):574-86. doi: 10.1002/jnr.23342. Epub 2014 Jan 21.
High-lipid diet composed of saturated fatty acids (SFAs) has significant detrimental effects on brain homeostasis, and deleterious effects of SFAs on various cells have been well documented. However, the effects of SFAs on neural stem Cells (NSCs) function have not been fully explored. The aim of this study was to determine whether palmitic acid (PA) affected the proliferation and differentiation of murine-derived NSCs. The results showed that PA dose dependently suppressed viability of NSCs and was cytotoxic at high concentrations. The toxic levels of PA inhibited the proliferation of NSCs as shown by reduced bromodeoxyuridine labeling of NSCs, which is correlated with reactive oxygen species generation. Pretreatment of the cells with the antioxidant N-acetyl-L-cysteine inhibitor significantly attenuated the effects of PA on the proliferation of NSCs. Furthermore, nontoxic levels of PA promoted astrocytogenesis in the differentiated NSCs, associated with Stat3 activation and altered expression of serial of basic helix-loop-helix transcription factor genes. Altogether, our data have demonstrated that PA has a significant impact on proliferation and differentiation of NSCs in vitro and may be useful for elucidating the role of SFAs in regulating NSCs fate in physiological and pathological settings.
由饱和脂肪酸（SFA）组成的高脂饮食对脑内环境稳定有显著的有害影响，并且SFA对各种细胞的有害作用已有充分记载。然而，SFA对神经干细胞（NSC）功能的影响尚未得到充分研究。本研究的目的是确定棕榈酸（PA）是否会影响源自小鼠的NSC的增殖和分化。结果表明，PA剂量依赖性地抑制NSC的活力，并且在高浓度时具有细胞毒性。PA的毒性水平抑制了NSC的增殖，如NSC的溴脱氧尿苷标记减少所示，这与活性氧的产生相关。用抗氧化剂N-乙酰-L-半胱氨酸抑制剂对细胞进行预处理可显著减弱PA对NSC增殖的影响。此外，无毒水平的PA促进分化的NSC中的星形胶质细胞生成，这与Stat3激活以及一系列碱性螺旋-环-螺旋转录因子基因的表达改变有关。总之，我们的数据表明PA在体外对NSC的增殖和分化有显著影响，可能有助于阐明SFA在生理和病理环境中调节NSC命运的作用。
