Mass Spectrometry Imaging Deciphers Dysregulated Lipid Metabolism in the Human Hippocampus Affected by Temporal Lobe Epilepsy

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 ( n = 14) and control (non-TLE; n = 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.