J Korean Neurol Assoc > Volume 20(2); 2002 > Article

Journal of the Korean Neurological Association 2002;20(2): 179-186.

"Kainate 유발 간질 모델에서 Glutamate 수용체의 시공간적인 분포와 M K - 8 0 1이 Glutamate 수용체의 활성에 미치는 영향; 정량적 수용체 자가방사법을 이용한 연구"

김명규 , 김병채 손의주 조기현 이민철

전남대학교 의과대학 신경과학교실, 의과학연구소

"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"

Myeong-Kyu Kim

Department of Neurology and Research Institute of Medical Science,Chonnam National University Medical School

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 binding 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 & 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 associated 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 & CA3. In addition, the synaptic reorganization in inner molecular layer of dentate gyrus was proved to be chronically hyperexcitable in function and may contribute epileptogenesis.Key Words : Kainic acid, Epileptogenesis, Autoradiography, Glutamate receptor"