Mass Spectrometric Imaging of Anionic Phospholipids Desorbed from Human Hippocampal Sections: Discrimination between Temporal and Nontemporal Lobe Epilepsies.

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 (n = 14) and non-TLE (control group; n = 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 (e.g., phosphatidylcholine and phosphatidylethanolamine, etc.) 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.