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. 2021 Nov 3;12(21):4187-4194. doi: 10.1021/acschemneuro.1c00587. Epub 2021 Oct 16.
Temporal lobe epilepsy (TLE) is the most prevalent form of human epilepsy, often accompanied by neurodegeneration in the hippocampus. Like other neurological diseases, TLE is expected to disrupt lipid homeostasis. However, the lipid architecture of the human TLE brain is relatively understudied, and the molecular mechanism of epileptogenesis is poorly understood. We performed desorption electrospray ionization mass spectrometry imaging of 39 fresh frozen surgical specimens of the human hippocampus to investigate lipid profiles in TLE with hippocampal sclerosis ( = 14) and control (non-TLE; = 25) groups. In contrast to several previous studies on animal models of epilepsy, we report reduced expression of various important lipids, notably phosphatidylcholine (PC) and phosphatidylethanolamine (PE), in the human TLE hippocampus. In addition, metabolic pathway analysis suggested the possible dysregulation of the Kennedy pathway in TLE, resulting in striking reductions of PC and PE levels. This revelation opens up opportunities to further investigate the associated molecular mechanisms and possible therapeutic targets for TLE.
颞叶癫痫（TLE）是最常见的人类癫痫形式，常伴有海马体的神经退行性变。与其他神经疾病一样，TLE 预计会破坏脂质动态平衡。然而，人类 TLE 大脑的脂质结构相对研究较少，癫痫发生的分子机制也知之甚少。我们对 39 个新鲜冷冻的人类海马体手术标本进行了解吸电喷雾电离质谱成像，以研究伴有海马硬化的 TLE（ = 14）和对照组（非 TLE； = 25）的脂质图谱。与之前关于癫痫动物模型的几项研究不同，我们报告在人类 TLE 海马体中，各种重要脂质，特别是磷脂酰胆碱（PC）和磷脂酰乙醇胺（PE）的表达减少。此外，代谢途径分析表明，TLE 中可能存在肯尼迪途径的失调，导致 PC 和 PE 水平的显著降低。这一发现为进一步研究 TLE 相关的分子机制和可能的治疗靶点提供了机会。
