Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy.
Analytical Biochemistry and Proteomics Laboratory, Research Centre on Aging and Translational Medicine (Ce.S.I-MeT), University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy.
Int J Mol Sci. 2018 Nov 14;19(11):3589. doi: 10.3390/ijms19113589.
Multiple sclerosis (MuS) is an autoimmune disease of the central nervous system characterized by neuroinflammation, neurodegeneration, and degradation of the myelin sheath. Epidemiological studies have shown that the female gender is more susceptible than the male gender to MuS development, with a female-to-male ratio of 2:1. Despite this high onset, women have a better prognosis than men, and the frequency of the relapsing phase decreases during pregnancy, while it increases soon after birth. Therefore, it is interesting to investigate hormonal fluctuations during pregnancy and whether they correlate with metabolic signatures. To gain a deeper inside into the biochemical mechanism of such a multifactorial disease, we adopted targeted metabolomics approaches for the determination of many serum metabolites in 12 pregnant women affected by MuS by mass spectrometry analysis. Our data show a characteristic hormonal fluctuation for estrogens and progesterone, as expected. They also highlight other interesting hormonal alterations for cortisol, corticosterone, 11-deoxycortisol, 4-androstene-3,17-dione, testosterone, and 17α-hydroxyprogesterone. Furthermore, a negative correlation with progesterone levels was observed for amino acids and for acylcarnitines, while an imbalance of different sphingolipids pathways was found during pregnancy. In conclusion, these data are in agreement with the characteristic clinical signs of MuS patients during pregnancy and, if confirmed, they may add an important tessera in the complex mosaic of maternal neuroprotection.
多发性硬化症(MuS)是一种中枢神经系统自身免疫性疾病,其特征是神经炎症、神经退行性变和髓鞘降解。流行病学研究表明,女性比男性更容易患上 MuS,女性与男性的比例为 2:1。尽管发病率如此之高,但女性的预后比男性好,怀孕期间复发期的频率降低,而产后则增加。因此,研究怀孕期间荷尔蒙波动及其与代谢特征的相关性是很有趣的。为了更深入地了解这种多因素疾病的生化机制,我们采用了靶向代谢组学方法,通过质谱分析测定了 12 名患有 MuS 的孕妇的许多血清代谢物。我们的数据显示,雌激素和孕激素的荷尔蒙波动特征与预期相符。它们还突出了其他有趣的荷尔蒙变化,如皮质醇、皮质酮、11-脱氧皮质醇、4-雄烯-3,17-二酮、睾酮和 17α-羟孕酮。此外,还观察到氨基酸和酰基辅酶 A 与孕激素水平呈负相关,而在怀孕期间发现不同的神经鞘脂代谢途径失衡。总之,这些数据与 MuS 患者怀孕期间的典型临床症状一致,如果得到证实,它们可能为母体神经保护的复杂马赛克增添一个重要的板块。