Department of Chemistry, Indian Institute of Science Education and Research Tirupati, Tirupati 517507, India.
Department of Neurological Sciences, Christian Medical College, Vellore 632004, India.
ACS Chem Neurosci. 2024 Mar 6;15(5):983-993. doi: 10.1021/acschemneuro.3c00693. Epub 2024 Feb 14.
Temporal lobe epilepsy (TLE) is one of the most common neurological disorders, often accompanied by hippocampal sclerosis. The molecular processes underlying this epileptogenesis are poorly understood. To examine the lipid profile, 39 fresh frozen sections of the human hippocampus obtained from epilepsy surgery for TLE ( = 14) and non-TLE (control group; = 25) patients were subjected to desorption electrospray ionization mass spectrometry imaging in the negative ion mode. In contrast to our earlier report that showed striking downregulation of positively charged phospholipids (, phosphatidylcholine and phosphatidylethanolamine, .) in the TLE hippocampus, this study finds complementary upregulation of negatively charged phospholipids, notably, phosphatidylserine and phosphatidylglycerol. This result may point to an active metabolic pool in the TLE hippocampus that produces these anionic phospholipids at the expense of the cationic phospholipids. This metabolic shift could be due to the dysregulation of the Kennedy and CDP-DG pathways responsible for biosynthesizing these lipids. Thus, this study further opens up opportunities to investigate the molecular hallmarks and potential therapeutic targets for TLE.
颞叶癫痫(TLE)是最常见的神经疾病之一,常伴有海马硬化。其致痫的分子过程尚不清楚。为了研究脂质谱,我们对 39 例来自 TLE(=14)和非 TLE(对照组;=25)患者癫痫手术的新鲜冷冻人脑海马组织进行了负离子模式解吸电喷雾电离质谱成像分析。与我们之前的报告相比,该报告显示 TLE 海马中带正电荷的磷脂(,磷脂酰胆碱和磷脂乙醇胺,。)明显下调,本研究发现带负电荷的磷脂,特别是磷脂酰丝氨酸和磷脂酰甘油互补地上调。这一结果可能表明 TLE 海马中存在活跃的代谢池,以牺牲阳离子磷脂为代价产生这些阴离子磷脂。这种代谢转变可能是由于负责合成这些脂质的 Kennedy 和 CDP-DG 途径失调所致。因此,这项研究进一步为研究 TLE 的分子特征和潜在治疗靶点提供了机会。