Hejr Hossein, Ghareghani Majid, Zibara Kazem, Ghafari Maryam, Sadri Farzad, Salehpour Zinab, Hamedi Azadeh, Negintaji Koresh, Azari Hassan, Ghanbari Amir
Cellular and Molecular Research Center, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran.
ER045, Laboratory of stem cells, DSST, Biology department, Faculty of Sciences-I, Lebanese University, Beirut, Lebanon.
Neurosci Lett. 2017 Jun 9;651:216-225. doi: 10.1016/j.neulet.2017.05.020. Epub 2017 May 11.
During neural development, embryonic neural stem cells (eNSCs) differentiate toward glial, oligodendrocytic, and neuronal cells. Dysregulation of polyunsaturated fatty acids (PUFAs) induce a wide range of neurological and developmental disorders. In this study, we investigated the effect of various concentrations and ratios of linoleic acid (LA) and alpha linolenic acid (ALA), which belong respectively to omega-6 and omega-3 PUFAs, on the proliferation and differentiation of eNSCs.Results showed that low (25 and 50μM) or high (100 and 200μM) concentrations of ALA, but not LA, and the ratio of 1:3 of LA/ALA significantly increased neurospheres size, frequency and cell numbers, in comparison to controls. Moreover, low or high concentrations of ALA, but not LA, and different ratios of LA/ALA resulted in a significant increase in mRNA expression levels of Notch1, Hes1 and Ki-67, and the differentiation of eNSCs toward astrocytes (GFAP) and oligodendrocytes (MBP), but not neurons (β-III Tubulin), with the highest increase being for LA/ALA ratio of 1:3, in comparison to controls. These results demonstrate the importance of higher concentrations of ALA in enhancing proliferation and differentiation of eNSCs, which could be used in diet to help preventing neurodevelopmental syndromes, cognitive decline during aging, and various psychiatric disorders.
在神经发育过程中,胚胎神经干细胞(eNSCs)向神经胶质细胞、少突胶质细胞和神经元细胞分化。多不饱和脂肪酸(PUFAs)的失调会引发多种神经和发育障碍。在本研究中,我们调查了分别属于ω-6和ω-3多不饱和脂肪酸的亚油酸(LA)和α-亚麻酸(ALA)的不同浓度和比例对eNSCs增殖和分化的影响。结果显示,与对照组相比,低浓度(25和50μM)或高浓度(100和200μM)的ALA而非LA,以及LA/ALA 1:3的比例显著增加了神经球的大小、频率和细胞数量。此外,低浓度或高浓度的ALA而非LA,以及不同比例的LA/ALA导致Notch1、Hes1和Ki-67的mRNA表达水平显著增加,并且eNSCs向星形胶质细胞(GFAP)和少突胶质细胞(MBP)分化,但不向神经元(β-III微管蛋白)分化,与对照组相比,LA/ALA比例为1:3时增加最为明显。这些结果证明了较高浓度的ALA在增强eNSCs增殖和分化方面的重要性,这可用于饮食中以帮助预防神经发育综合征、衰老过程中的认知衰退以及各种精神疾病。