Inhibition of mammalian target of rapamycin complex 1 signaling by n-3 polyunsaturated fatty acids promotes locomotor recovery after spinal cord injury

n-3 多不饱和脂肪酸抑制哺乳动物雷帕霉素靶蛋白复合物 1 信号传导可促进脊髓损伤后运动功能恢复

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作者:Jiping Nie #, Jian Chen #, Jianguo Yang #, Qinqin Pei #, Jing Li, Jia Liu, Lixin Xu, Nan Li, Youhao Chen, Xiaohua Chen, Hao Luo, Tiansheng Sun

Abstract

The present study aimed to explore the effects of n‑3 polyunsaturated fatty acids (PUFAs) on autophagy and their potential for promoting locomotor recovery after spinal cord injury (SCI). Primary neurons were isolated and cultured. Sprague‑Dawley rats were randomly divided into three groups and fed diets with different amounts of n‑3 PUFAs. A model of spinal cord contusion was created at the T10 spinal segment and the composition of PUFAs was analyzed using gas chromatography. Spinal repair and motor function were evaluated postoperatively. Assessment of the effects of n‑3 PUFAs on autophagy and mammalian target of rapamycin complex 1 (mTORC1) was performed using immunofluorescence staining and western blotting. In vitro, n‑3 PUFAs inhibited mTORC1 and enhanced autophagy. The n‑3 PUFA levels and the ratio of n‑3 PUFA to n‑6 PUFA in the spinal cord and serum of rats fed a high‑n‑3 PUFA diet were higher before and after operation (P<0.05). Additionally, rats in the high‑n‑3 PUFA group showed improved motor function recovery, spinal cord repair‑related protein expression level (MBP, Galc and GFAP). Expression levels if these protiens in the high‑n‑3 PUFA diet group expressed the highest levels, followed by the low‑n‑3 PUFA diet group and finally the control group (P<0.05). high‑n‑3 PUFA diet promoted autophagy ability and inhibited activity of the mTORC1 signaling pathway compared with the low‑n‑3 PUFA diet group or the control group (P<0.05). These results suggest that exogenous dietary n‑3 PUFAs can inhibit mTORC1 signaling and enhance autophagy, promoting functional recovery of rats with SCI.

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