Evaluation of sphingolipids changes in brain tissues of rats with pentylenetetrazol-induced kindled seizures using MALDI-TOF-MS

Abnormal lipid metabolism has been implicated in the pathogenesis of many neural system diseases, including epilepsy. Pentylenetetrazol (PTZ)-induced kindling in rodents is considered a model of human absence epilepsy and myoclonic, generalized tonic-clonic seizure. In an effort to further understand the mechanism for PTZ-induced seizure, we analyzed crude lipids and sphingolipids in the cortex, hippocampus, and brain stem of normal and PTZ-rats using delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry (DE MALDI-TOF-MS). It was found that phosphatidylcholines dominated the crude lipids in different tissues and there were no obvious differences in crude lipid profiles of different tissues between normal and PTZ-rats. However, ceramide, sphingomyelins, and ceramide-monohexoside were differently distributed in normal and PTZ-rats. Using the reference mass spectra method established in our laboratory, it was shown that sphingomyelins and ceramide-monohexoside levels were elevated in the brain tissues of PTZ-rats. Ceramide levels were found to be higher in brain stem than in cortex and hippocampus of normal rats, and PTZ caused a general decrease in ceramide levels. These data suggest that changes in sphingolipid metabolism contribute to PTZ-induced seizure.