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Electroconvulsive Seizures in Rats and Fractionation of Their Hippocampi to Examine Seizure-induced Changes in Postsynaptic Density Proteins
Published on: August 15, 2017
Alteration of epileptogenesis genes
Amy R Brooks-Kayal1, Yogendra H Raol, Shelley J Russek
1Division of Neurology, Department of Pediatrics, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA. brooks-kayal.amy@tchden.org
Summary
Epilepsy development (epileptogenesis) involves gene expression changes. Targeting GABA(A) receptor changes after seizures may prevent epilepsy, offering new therapeutic strategies.
Area of Science:
- Neuroscience
- Molecular Biology
- Epilepsy Research
Background:
- Precipitating events like seizures, stroke, or head trauma can lead to epilepsy.
- Epileptogenesis involves complex changes in gene expression, making it challenging to identify causal factors.
- The GABA(A) receptor is crucial for fast synaptic inhibition, and its altered expression is implicated in epilepsy.
Purpose of the Study:
- To investigate the role of GABA(A) receptor subunit alterations in epileptogenesis.
- To identify molecular mechanisms regulating GABA(A) receptor expression after seizures.
- To explore therapeutic targets for preventing epilepsy development.
Main Methods:
- Studied changes in GABA(A) receptor subunit expression and function post-status epilepticus (SE) in animal models.
- Utilized viral gene transfer to prevent GABA(A) receptor subunit changes after SE.
- Investigated signaling pathways (CREB-ICER, JAK-STAT, BDNF, Egr3) regulating gene expression.
Main Results:
- GABA(A) receptor subunit expression and function change after SE and persist in chronic epilepsy.
- Preventing these GABA(A) receptor changes via gene transfer inhibited epilepsy development in an animal model.
- Identified CREB-ICER, JAK-STAT, BDNF, and Egr3 signaling pathways as regulators of GABA(A) receptor subunit expression.
Conclusions:
- Alterations in GABA(A) receptor subunits directly contribute to epileptogenesis.
- Targeting specific signaling pathways offers a potential strategy for preventing or treating epilepsy after an initial insult.
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