J Korean Neurol Assoc.  2002 Mar;20(2):179-186.

The Temporospatial Distribution of Glutamate Receptors and the Effect of MK-801 on Glutamate Receptors Activation in Kainate-induced Seizure Model: Quantitative Receptor Autoradiography of Ionotropic Glutamate Receptors

• Kim MK
• Kim BC
• Sohn EJ
• Cho KH
• Lee MC

Abstract

BACKGROUND: Excitotoxicity and epileptogenesis have often been associated with glutamate receptor activation. Some evidence indicates that selective down regulation of AMPA receptor may be the mechanism of delayed neuronal cell death in the hippocampus.
METHODS
We used in situ hybridization to examine the hybridization density (HD) of NMDA and AMPA receptors on excitotoxicity and epileptogenesis in the hippocampus of the kainic acid (KA)-induced rat seizure model. Some Sprague-Dawley rats were injected with KA, and others with MK-801 prior to KA injection. The rats were killed at 8 hours or 4 weeks after KA or MK-801/KA injection. HD of [3H]MK-801 and [3H]AMPA bind-ing in subfields of the hippocampus was measured by an image analyzer.
RESULTS
After 8 hours of KA injection, [3H]MK-801 binding was increased in CA1 and CA3, and decreased in dentate gyrus, and [3H]AMPA binding was decreased in all of CA1, CA3 and fascia dentata, and pretreatment of MK-801 did not affect [3H]AMPA binding in all of CA1, CA3 and dentate gyrus. After 4 weeks, both [3H]MK-801 and [3H]AMPA binding were prominently increased in inner molecular layer of dentate gyrus.
CONCLUSIONS
Glutamate receptors, especially NMDA receptor, were associ-ated with excitotoxicity in the hippocampus but the selective down regulation of GluR2 subunit of AMPA receptor without NMDA receptor activation may not be sufficient to cause excitotoxic neuronal cell death in CA1 and CA3. In addition, the synaptic reorganization in inner molecular layer of dentate gyrus was proved to be chronically hyperex-citable in function and may contribute epileptogenesis.

Keyword

Kainic acid; Epileptogenesis; Autoradiography; Glutamate receptor

MeSH Terms

Animals
Autoradiography*
Cell Death
Dentate Gyrus
Dizocilpine Maleate*
Down-Regulation
Glutamic Acid*
Hippocampus
In Situ Hybridization
Kainic Acid
N-Methylaspartate
Neurons
Rats
Rats, Sprague-Dawley
Receptors, AMPA
Receptors, Glutamate*
Receptors, Ionotropic Glutamate*
Seizures*
Dizocilpine Maleate
Glutamic Acid
Kainic Acid
N-Methylaspartate
Receptors, AMPA
Receptors, Glutamate
Receptors, Ionotropic Glutamate