Lauric acid promotes neuronal maturation mediated by astrocytes in primary cortical cultures
Lauric acid promotes neuronal maturation mediated by astrocytes in primary cortical cultures
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DOI：
10.1016/j.heliyon.2020.e03892
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发表时间：
2020-05-01
期刊：
影响因子：
4
通讯作者：
Kunugi, Hiroshi
中科院分区：
文献类型：
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作者：
Nakajima, Shingo;Kunugi, Hiroshi
以前的研究表明，中链脂肪酸(MCFA)在治疗情绪障碍和认知功能障碍方面具有潜在的疗效。在星形胶质细胞中，MCFAs被代谢成酮体；然而，它们对神经元发育包括神经营养因子水平的影响还不是很清楚。在本研究中，我们检测了MCFAs对原代培养的皮质星形胶质细胞生长因子和细胞因子mRNA表达的影响。采用共培养和星形胶质细胞条件培养液检测MCFAs对神经元成熟过程中神经元-星形胶质细胞相互作用的影响。月桂酸(LA)显著增加星形胶质细胞胶质源性神经营养因子(GDNF)、白介素6(IL6)和C-C基序趋化因子2(CCL(2))的mRNA表达。La诱导的胞外信号调节激酶的磷酸化导致了这些变化。在含有星形胶质细胞的皮质神经元的原代培养中，LA提高了突触前蛋白水平。LA处理后的星形胶质细胞条件培养液也提高了皮层神经元培养的突触前蛋白水平。以上结果提示，LA可促进星形胶质细胞GDNF和细胞因子的基因表达，从而促进突触前成熟。
Previous studies have suggested the potential efficacy of middle chain fatty acids (MCFAs) in the treatment of mood disorders and cognitive dysfunction. MCFAs are metabolized to ketone bodies in astrocytes; however, their effects on neuronal development including neurotrophic factor level are not well-understood. In the present study, we examined the effect of MCFAs on the mRNA expression of growth factors and cytokines in primary cultures of cortical astrocytes. The effect of MCFAs on neuron-astrocyte interaction in neuronal maturation was also determined using co-culture and astrocyte-conditioned medium. Lauric acid (LA) typically increased the mRNA expression of glial-derived neurotrophic factor (Gdnf), interleukin-6 (Il6), and C-C motif chemokine 2 (Ccl(2)) in astrocytes. LA-induced phosphorylation of extracellular signal-regulated kinase contributed to these changes. In primary cultures of cortical neurons containing astrocytes, LA enhanced the presynaptic protein levels. Astrocyte-conditioned medium after LA treatment also enhanced the presynaptic protein levels in the cortical neuron cultures. These results suggest that LA increase the mRNA expression of GDNF and cytokines in astrocytes, and thereby, enhances the presynaptic maturation.