cDNA Profiling of Epileptogenesis-Related Genes: Focus on Membrane Type Metalloproteinase 1.
Abstract number :
2.085
Submission category :
Year :
2001
Submission ID :
224
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
K. Lukasiuk, PhD, A.I. Virtanen Institute, University of Kuopio, Kuopio, Finland; A. Pitkänen, MD, PhD, A I. Virtanen Institute, Universtiy of Kuopio, Kuopio, Finland
RATIONALE: Epilepsy frequently develops as a result of brain insult and the epileptic process can be divided into three phases: 1) initial insult, 2) latency period (epileptogenesis) and 3) recurrent seizures (epilepsy). In the present study, we aimed at identification of epileptogenesis related genes.
METHODS: We used an amygdala stimulation model of the temporal lobe epilepsy, in which status epilepticus (SE) is followed by a latency period preceding the appearance of the first spontaneous seizures. SE was evoked by stimulation of the lateral nucleus of the amygdala. Rats were monitored with video-EEG during SE, and thereafter, until the end of the experiment to detect the appearance of spontaneous seizures. Rats were sacrificed and tissue was collected 2 weeks after stimulation. Comparison of transcriptosomes was performed using cDNA arrays. Changes in gene expression were confirmed with semiquantitative RT-PCR and immunohistochemistry.
RESULTS: Analysis of data obtained from cDNA array hybridization of hippocampal RNA from control (unstimulated) rats and rats undergoing epileptogenesis (that had SE but did not experience spontaneous seizures yet) revealed upregulation of nine genes coding for proteinases or their inhibitors including a membrane type matrix metalloproteinase 1 (MT1-MMP). Epileptogenesis-related increase in MT1-MMP expression was confirmed with semiquantitative RT-PCR. Increase in MT1-MMP protein was observed in the inner molecular layer of the dentate gyrus, as revealed by immunohistochemistry.
CONCLUSIONS: MT1-MMP regulating the remodeling of extracellular matrix may participate in SE induced plasticity leading to development of epilepsy.
Support: Supported by the Academy of Finland, Sigrid Juselius Foundation and Vaajasalo Foundation.