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MK-801 does not attenuate immediate-early gene expression following an amygdala afterdischarge
P Hughes1, K Singleton, M Dragunow
1Department of Pharmacology, School of Medicine, University of Auckland, New Zealand.
Abstract:
It has been suggested that the increased transient expression of immediate-early gene transcription factors seen in nerve cells following an afterdischarge may initiate longer lasting or permanent changes in gene expression which underly the development of kindling. Since the development of kindling is sensitive to pharmacological blockade of the N-methyl-D-aspartate receptor, we tested whether the increased expression of the immediate-early genes c-fos, jun-B, c-jun, krox-20, and krox-24 following a kindling afterdischarge was also sensitive to N-methyl-D-aspartate receptor blockade by MK-801. In this report we demonstrate that all five immediate-early genes are induced by an amygdala afterdischarge. N-methyl-D-aspartate receptor blockade by a dose of MK-801 that significantly retards the development of amygdala kindling failed to attenuate immediate-early gene expression. These results suggest that although expression of these five immediate-early genes occurs after an amygdala afterdischarge their expression is not involved in the N-methyl-D-aspartate receptor-mediated component of amygdala kindling.
Insights
Immediate-early gene expression after brain afterdischarges is not blocked by NMDA receptor antagonists. This suggests these genes are not involved in the NMDA receptor-dependent development of kindling.
Area of Science:
- Neuroscience
- Molecular Biology
- Epilepsy Research
Background:
- Kindling is a model for epilepsy development.
- Immediate-early genes (IEGs) are rapidly expressed after neuronal stimulation.
- IEG expression may underlie long-term changes in gene expression leading to kindling.
Purpose of the Study:
- To investigate if IEG induction following an afterdischarge is sensitive to N-methyl-D-aspartate (NMDA) receptor blockade.
- To determine the role of NMDA receptor-dependent IEG expression in amygdala kindling.
Main Methods:
- Kindling was induced in the amygdala.
- Afterdischarges were monitored.
- Expression of five immediate-early genes (c-fos, jun-B, c-jun, krox-20, krox-24) was measured.
- Mice were treated with MK-801, an NMDA receptor antagonist, to assess its effect on IEG expression and kindling development.
Main Results:
- An amygdala afterdischarge induced the expression of all five tested immediate-early genes.
- NMDA receptor blockade with MK-801 significantly retarded kindling development.
- However, the same dose of MK-801 failed to attenuate the expression of the immediate-early genes induced by the afterdischarge.
Conclusions:
- The induction of c-fos, jun-B, c-jun, krox-20, and krox-24 following an amygdala afterdischarge is not dependent on the NMDA receptor.
- These specific immediate-early genes are likely not involved in the NMDA receptor-mediated component of amygdala kindling development.