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

Abstract

Neuronal loss, gliosis and axonal sprouting in the hippocampal formation are characteristics of the syndrome of mesial temporal sclerosis (MTS). In the post-status epilepticus (SE) rat model of spontaneous seizures these features of the MTS syndrome can be reproduced. To get a global view of the changes in gene expression in the hippocampus we applied serial analysis of gene expression (SAGE) during the early phase of epileptogenesis (latent period), 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 mRNA transcript. Of these, 92 genes were differentially expressed in the hippocampus of post-SE rats in comparison to controls. These genes appeared to be mainly associated with ribosomal proteins, protein processing, axonal growth and glial proliferation proteins. Verification of two of the differentially expressed genes by in situ hybridization confirmed the changes found by SAGE. Histological analysis of hippocampal sections obtained 8 days after SE showed extensive cell loss, mossy fibre sprouting and gliosis in hippocampal sub regions. This study identifies new high-abundant genes that may play an important role in post-SE epileptogenesis.

Electroconvulsive Seizures Regulate Gene Expression of Distinct Neurotrophic Signaling Pathways

“…Exercise, and most of these 11 genes, are associated with neuroprotection, neuroplasticity, and antidepressant effects rather than with damage. In addition, none of the other 107 genes in Table 1 overlapped with the 92 genes reported by Hendriksen et al (2001) to be altered in the gliotic and degenerate hippocampus in a status epileptics model. The present study is the first to demonstrate with high-density microarrays genomic changes in response to acute and chronic electroconvulsive seizure.…”

“…Investigations into the mediators of ECS have evaluated one or, at most, only several mRNA species in any brain region (Table A; available at http://www.psygenomics.com/html/Supplemental_ Table_A.pdf). Hendriksen et al (2001) measured multiple gene expression changes in the hippocampus, but only 8 d after local seizures induced by electrical stimulation had been terminated by pentobarbital. The only other study of this kind was by Lukasiuk et al (2003), in which hippocampal and temporal lobe expression profiling was conducted in animals subjected to amygdala kindling but before they developed spontaneous seizures.…”

Genes e epilepsia II: expressão gênica diferencial

“…A maior parte dos genes alterados está envolvida em vias metabólicas não-associadas previamente a crises convulsivas. Em particular, o gene da cistatina C, um inibidor de proteases, apresentou-se aproximadamente cinco vezes mais expresso em hipocampos de ratos submetidos às crises 42,43 . Nas análises de hibridação subtrativa, cDNAs provenientes de uma amostra A (hipocampo epiléptico) são subtraídos de cDNAs provenientes de uma amostra B (hipocampo normal).…”

Cystatin C Rescues Degenerating Neurons in a Cystatin B-Knockout Mouse Model of Progressive Myoclonus Epilepsy

“…[15][16][17] Notably, CysC has been implicated in the processes of neuronal repair of the nervous system. Enhanced CysC expression was observed in response to injury, including transient forebrain ischemia, 18,19 seizures, 20 and induction of epilepsy. 20 -22 Oxidative stress also stimulates an increase in CysC expression in cultured rat primary neurons 23 and in cerebral microvascular smooth muscle cells in vitro.…”