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转录组学和代谢组学分析提供了神经酸通过 MPTP 刺激 PD 模型小鼠减轻神经炎症的见解。

Transcriptomic and metabolomic analyses provide insights into the attenuation of neuroinflammation by nervonic acid in MPTP-stimulated PD model mice.

机构信息

College of Life Science, Northwest Normal University, Lanzhou 730070, Gansu Province, China.

Bioactive Products Engineering Research Center for Gansu Distinctive Plants, Lanzhou 730070, China.

出版信息

Food Funct. 2023 Jan 3;14(1):277-291. doi: 10.1039/d2fo02595g.

DOI:10.1039/d2fo02595g
PMID:36484706
Abstract

Nervonic acid is one of the most promising bioactive fatty acids, which is believed to be beneficial for the recovery of human cognitive disorders. However, the detailed neuroprotective effects and mode of action of nervonic acid have not yet been fully elucidated. In this study, we used an MPTP-stimulated mouse Parkinson's disease (PD) model as a target to investigate the neuroprotective effects by behavioral tests and integrative analysis of trancriptomes and metabolomes of PD mouse brain with nervonic acid injections. The KEGG pathway enrichment analysis of transcriptomes showed that the genes involved in neuroinflammation were significantly increased after MPTP induction and have been greatly inhibited by nervonic acid injection, while nervonic acid also greatly improved nerve growth and synaptic plasticity pathways which were significantly downregulated by MPTP. At the same time, the upregulation of oleic acid and arachidonic acid metabolism pathways and the downregulation of amino acid metabolism pathways in metabolomes were particularly highlighted in the nervonic acid protection groups compared with the PD model. Meanwhile, it was found that arachidonic acid, oleic acid and taurine play an important regulatory role in the neuroprotective mechanism of nervonic acid through fatty acid metabolism by integrative analysis. Therefore, our study laid a solid foundation for further studies on the specific role of nervonic acid in the inhibition of PD at the level of metabolic regulation.

摘要

神经酸是最有前途的生物活性脂肪酸之一,据信它对人类认知障碍的恢复有益。然而,神经酸的详细神经保护作用和作用机制尚未完全阐明。在这项研究中,我们使用 MPTP 刺激的小鼠帕金森病 (PD) 模型作为靶点,通过行为测试和对 PD 小鼠大脑转录组和代谢组的综合分析,研究神经酸注射的神经保护作用。转录组的 KEGG 通路富集分析表明,MPTP 诱导后,参与神经炎症的基因显著增加,而神经酸注射大大抑制了这些基因的表达,同时,神经酸还显著改善了由 MPTP 显著下调的神经生长和突触可塑性通路。同时,在代谢组学中,特别突出了神经酸保护组中油酸和花生四烯酸代谢途径的上调以及氨基酸代谢途径的下调。同时,通过整合分析发现,花生四烯酸、油酸和牛磺酸通过脂肪酸代谢在神经酸的神经保护机制中发挥重要的调节作用。因此,我们的研究为进一步研究神经酸在代谢调节水平抑制 PD 的具体作用奠定了基础。

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