Loonen Inge C M, Kohler Isabelle, Ghorasaini Mohan, Giera Martin, van den Maagdenberg Arn M J M, Mayboroda Oleg A, Tolner Else A
Department of Human Genetics, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands.
Center for Proteomics and Metabolomics, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands.
Metabolites. 2022 Mar 1;12(3):220. doi: 10.3390/metabo12030220.
Metabolite levels in peripheral body fluids can correlate with attack features in migraine patients, which underscores the potential of plasma metabolites as possible disease biomarkers. Migraine headache can be preceded by an aura that is caused by cortical spreading depolarization (CSD), a transient wave of neuroglial depolarization. We previously identified plasma amino acid changes after CSD in familial hemiplegic migraine type 1 (FHM1) mutant mice that exhibit increased neuronal excitability and various migraine-related features. Here, we aimed to uncover lipid metabolic pathways affected by CSD, guided by findings on the involvement of lipids in hemiplegic migraine pathophysiology. Using targeted lipidomic analysis, we studied plasma lipid metabolite levels at different time points after CSD in wild-type and FHM1 mutant mice. Following CSD, the most prominent plasma lipid change concerned a transient increase in PGD, which lasted longer in mutant mice. In wild-type mice only, levels of anti-inflammatory lipid mediators DPAn-3, EPA, ALA, and DHA were elevated 24 h following CSD compared to Sham-treated animals. Given the role of PGs and neuroinflammation in migraine pathophysiology, our findings underscore the potential of monitoring peripheral changes in lipids to gain insight in central brain mechanisms.
外周体液中的代谢物水平可能与偏头痛患者的发作特征相关，这突出了血浆代谢物作为潜在疾病生物标志物的可能性。偏头痛发作前可能会出现由皮质扩散性抑制（CSD）引起的先兆，CSD是一种神经胶质去极化的短暂波。我们之前在表现出神经元兴奋性增加和各种偏头痛相关特征的1型家族性偏瘫性偏头痛（FHM1）突变小鼠中，发现了CSD后血浆氨基酸的变化。在此，鉴于脂质参与偏瘫性偏头痛病理生理学的研究结果，我们旨在揭示受CSD影响的脂质代谢途径。通过靶向脂质组学分析，我们研究了野生型和FHM1突变小鼠在CSD后不同时间点的血浆脂质代谢物水平。CSD后，最显著的血浆脂质变化是PGD的短暂增加，这在突变小鼠中持续时间更长。仅在野生型小鼠中，与假手术处理的动物相比，CSD后24小时抗炎脂质介质DPAn-3、EPA、ALA和DHA的水平升高。鉴于PGs和神经炎症在偏头痛病理生理学中的作用，我们的研究结果突出了监测外周脂质变化以深入了解中枢脑机制的可能性。
