Altered hippocampal gene expression prior to the onset of spontaneous seizures in the rat post-status epilepticus model

Neuronal loss, gliosis and axonal sprouting in the hippocampal formation ar e characteristics of the syndrome of mesial temporal sclerosis (MTS). In th e post-status epilepticus (SE) rat model of spontaneous seizures these feat ures of the MTS syndrome can be reproduced. To get a global view of the cha nges in gene expression in the hippocampus we applied serial analysis of ge ne expression (SAGE) during the early phase of epileptogenesis (latent peri od), prior to the onset of the first spontaneous seizure. A total of 10 000 SAGE tags were analyzed per experimental group, resulting in 5053 (SE) and 5918 (control group) unique tags (genes), each representing a specific mRN A transcript. Of these, 92 genes were differentially expressed in the hippo campus of post-SE rats in comparison to controls. These genes appeared to b e mainly associated with ribosomal proteins, protein processing, axonal gro wth and glial proliferation proteins. Verification of two of the differenti ally expressed genes by in situ hybridization confirmed the changes found b y SAGE. Histological analysis of hippocampal sections obtained 8 days after SE showed extensive cell loss, mossy fibre sprouting and gliosis in hippoc ampal sub regions. This study identifies new high-abundant genes that may p lay an important role in post-SE epileptogenesis.