2002 Fiscal Year Final Research Report Summary
Involvement of GABA-mediated inhibitory neuronal processes in seizure activity in rat hippocampal slices
| Project/Area Number |
13670994
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Kanazawa university |
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Principal Investigator |
HIGASHIMA Masato Kanazawa University Hospital Assistant Professor, 医学部附属病院, 講師 (00173146)
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| Project Period (FY) |
2001 – 2002
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| Keywords | epilepsy / kindling / hippocampus / brain slice / inhibitory synaptic trasmission / disinhibiton / afterdischarge / GABA |
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| Research Abstract |
The main purpose of our study is to clarify the involvement of γ-aminobutric acid (GABA)-mediated inhibitory mechanism in generation of seizure activity of epilepsy. We used an in vitro seizure model, in which ictal activity-like rhythmic afterdischarges (Ads) are developmentally induced following repetitive application of high-frequency stimuli (1 sec, 100 Hz) to the stratum radiatum of the CA1 region in rat hippocampal slices. We have previously reported that the GABA_A receptor antagonist bicuculline suppresses AD generation, suggesting that activation of GABA_A-mediated inhibitory mechanism may be necessary for ictal activity.
In order to test whether this model can serve as an in vitro seizure model for temporal lobe epilepsy, we examined the effects of antiepileptic drugs on this model. Bath application of phenytoin and carbamazepine, which are clinically effective against seizures associated with temporal lobe epilepsy, suppressed AD generation at their clinically relevant concentrations. On the other hand, ethosuximide which is clinically effective against absence seizure but not against temporal lobe epilepsy had no effect on AD generation at its clinically relevant concentration. These findings suggest that our experimental model can become an experimental seizure model for temporal lobe epilepsy. In addition, we recorded intracellular potentials of pyramidal neurons in the CA1 region. Following repetitive high-frequency stimulation to the CA1 stratum radiatum, the amplitude of GABA_A-mediated inhibitory postsynaptic potentials induced by single stimuli increased in conjunction with enhancement in AD generation. Therefore we conclude that activation of GABA_A-mediated inhibitory processes is necessary for seizure induction of temporal lobe epilepsy, and propose a modification to the simple disinhibition hypothesis for epileptogenesis.
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Research Products
(4 results)
