cDNA PROFILING OF EPILEPTOGENESIS IN THE RAT BRAIN
Abstract number :
1.047
Submission category :
Year :
2002
Submission ID :
458
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Katarzyna Lukasiuk, Laura Kontula, Asla Pitkanen. A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland
RATIONALE: Temporal lobe epilepsy is the most common human focal epilepsy. It typically develops in three phases: (1) initial brain damaging insult, (2) latency period (epileptogenesis), (2) recurrent seizures (epilepsy). The present study tested the hypothesis that remodeling of neuronal circuits underlying epilepsy is associated with altered gene expression during the epileptogenic phase.
METHODS: Epileptogenesis was triggered by inducing self-sustained status epilepticus (SSSE) with a 20 to 30 min electrical stimulation of the amygdala in rats. Animals were monitored continuously with video-EEG to ascertain that they were in the epileptogenic phase. Pattern of gene expression was examined in the hippocampus and temporal lobe using cDNA arrays containing about 5000 gene probes. Semiquantitative RT-PCR was performed to verify changes in expression for selected genes.
RESULTS: Changes in gene expression were found for 282 genes. In the hippocampus 87 genes displayed changes in expression. In animals undergoing epileptogenesis, that did not have spontaneous seizures changes in gene expression were observed for 37 genes at 1 day, 12 genes at 4 days, and 14 genes at 14 days after stimulation. In epileptic animals, that had spontaneous seizures by 14d after stimulation alterations were observed for 42 genes. In the temporal lobe changes in expression were observed for 208 genes. In animals undergoing epileptogenesis, changes in gene expression were observed for 29 genes at 1 day, 155 genes at 4 days, and 32 genes at 14 days after stimulation. In epileptic animals alterations were observed for 62 genes. Genes displaying changes can participate in a wide range of processes including synaptic and axonal plasticity, organization of cytoskeleton, organization of extracellular matrix or cell adhesion, gliosis, signal transduction, protein synthesis and processing, energy metabolism, regulation of cell cycle, or oxidative processes. Majority of these genes was not previously implicated in epileptogenesis or epilepsy or encodes unknown proteins.
CONCLUSIONS: Epileptogenesis is associated with dynamic changes in expression of number of genes that can be involved in several parallel processes occurring in the brain.
[Supported by: the Academy of Finland, Sigrid Juselius Foundation and Vaajasalo Foundation.]