Alterations in hippocampal myelin and oligodendrocyte precursor cells during epileptogenesis

Recent reports have described damage to myelinated fibers in the central nervous system (CNS) in patients with temporal lobe epilepsy (TLE) and animal models. However, only limited data are available on the dynamic changes that occur in myelinated fibers, oligodendrocytes (which are myelin-forming cells), and oligodendrocyte precursor cells (OPCs), which are a reservoir of new oligodendrocytes, in the hippocampus throughout epileptogenesis. The current study was designed to examine this issue using a rat model of lithium-pilocarpine-induced epilepsy. Electroencephalography (EEG), immunofluorescence, and Western blot analysis showed that the loss of myelin and oligodendrocytes in the rat hippocampus began during the acute stage of epileptogenesis, and the severity of this loss increased throughout epileptogenesis. Accompanying this loss of myelin and oligodendrocytes, OPCs in the rat hippocampus became activated and their populations increased during several phases of epileptogenesis (the acute, latent and chronic phases). The transcription factors olig1 and olig2, which play crucial roles in regulating OPC proliferation, differentiation and remyelination, were up-regulated during the early phases (the acute and latent phases) followed by a sharp decline in their expression during the chronic and late chronic phases. This study is the first to confirm the loss of myelin and oligodendrocytes during lithium-pilocarpine-induced epileptogenesis accompanied by a transient increase in the number of OPCs. Prevention of the loss of myelin and oligodendrocytes may provide a novel treatment strategy for epilepsy.