Comprehensive Analysis of Age-related Changes in Lipid Metabolism and Myelin Sheath Formation in Sciatic Nerves
Comprehensive Analysis of Age-related Changes in Lipid Metabolism and Myelin Sheath Formation in Sciatic Nerves
复制标题
坐骨神经脂质代谢和髓鞘形成的年龄相关变化的综合分析。
DOI：
10.1007/s12031-020-01768-5
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发表时间：
2021-01-25
影响因子：
3.1
通讯作者：
Zhu, Zhaowei
中科院分区：
文献类型：
--
作者：
Djuanda, David;He, Bo;Zhu, Zhaowei
目的探讨衰老过程中大鼠坐骨神经髓鞘形成和脂质代谢的分子变化。健康雄性SD大鼠36只，按日龄分为1周龄、1月龄、6月龄、12月龄和24月龄5组。收集1月龄和24月龄SD大鼠坐骨神经（n = 3）进行下一代测序（NGS）和生物信息学分析。收获来自每组的标本并通过qPCR、蛋白质印迹和透射电子显微镜（TEM）进行分析。构建了与髓鞘和脂质代谢相关的差异表达mRNA（DEmRNA）的蛋白质-蛋白质相互作用（PPI）网络。使用qPCR验证子网络中的DEmRNA。在衰老过程中共发现4580个DEmRNA。最高富集的GO生物过程主要聚集在胆固醇和脂质代谢中，包括胆固醇生物合成过程（RF = 3.16），甾醇生物合成过程（RF = 3.03），胆固醇代谢过程（RF = 2.15）、甾醇代谢过程（RF = 2.11）、脂肪酸生物合成过程（RF = 2.09）和脂质生物合成过程（RF = 1.79）。MBP、PMP 22和MPZ的mRNA水平在衰老过程中呈下降趋势，而MBP的蛋白表达呈上升趋势。透射电镜结果显示，1周龄大鼠髓鞘变薄，无髓轴突数量增加，老年大鼠髓鞘变厚，轴突变性。构建了40个与脂质代谢相关的PPI子网络，包括一个初级子网络和两个较小的子网络。枢纽基因是子网络1中的mTOR、子网络2中的Akt 1和子网络3中的SIRT 1。没有发现与测序结果一致的基因表达，而在下调的基因中，AKT 1，CEBPA，LIPE，LRP 5，PHB和Rara在24月龄大鼠中显著下调。脂代谢可能在维持坐骨神经结构和生理功能方面起重要作用，可作为神经老化研究的候选对象。
To investigate the molecular changes related to myelin formation and lipid metabolism in the sciatic nerve in Sprague Dawley (SD) rats during aging. Thirty-six healthy male SD rats were divided into five groups according to age: 1 week, 1 month, 6 months, 12 months, and 24 months. Sciatic nerves were collected from 1-month-old and 24-month-old SD rats (n = 3) to perform next-generation sequencing (NGS) and bioinformatics analysis. Specimens from each group were harvested and analyzed by qPCR, Western blotting, and transmission electron microscopy (TEM). Protein-protein interaction (PPI) networks of differentially expressed mRNAs (DEmRNAs) related to myelin and lipid metabolism were constructed. DEmRNAs in subnetworks were verified using qPCR. A total of 4580 DEmRNAs were found during aging. The top enriched GO biological processes were primarily clustered in cholesterol and lipid metabolism, including the cholesterol biosynthetic process (RF = 3.16), sterol biosynthetic process (RF = 3.03), cholesterol metabolic process (RF = 2.15), sterol metabolic process (RF = 2.11), fatty acid biosynthetic process (RF = 2.09), and lipid biosynthetic process (RF = 1.79). The mRNA levels of MBP, PMP22, and MPZ were downregulated during aging, while the protein expression of MBP showed an increasing trend. The TEM results showed thin myelin sheaths and an increased number of unmyelinated axons in the 1-week-old rats, and the sheaths became thickened with degenerated axons appearing in older animals. Forty PPI subnetworks related to lipid metabolism were constructed, including one primary subnetwork and two smaller subnetworks. The hub genes were mTOR in sub-network 1, Akt1 in sub-network 2, and SIRT1 in sub-network 3. No gene expression was found consistent with the sequencing results, while in the downregulated genes, AKT1, CEBPA, LIPE, LRP5, PHB, and Rara were significantly downregulated in 24-month-old rats. Lipid metabolism might play an important role in maintaining the structure and physiological function in sciatic nerves during aging and could be candidates for nerve aging research.