1997 Fiscal Year Final Research Report Summary
Characterization of molecular events leading to seizure susceptibility in ethacrynic acid-induced seizure model.
| Project/Area Number |
08680850
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Kansai Medical University |
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Principal Investigator |
OMORI Kyoko Kansai Medical Univ., Dept.of Pharmacol., Assistant Professor, 医学部, 助教授 (90152256)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Ethacrynic acid / c-fos / nerve growth factor (NGF) / generalized tonic-clomic convulsion / hippocampus / seizure susceptibility / inhibitory interneuron |
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| Research Abstract |
Neuronal alterations by seizures produce a long-lasting reorganization of susceptible neuronal circuity in the central nervous system, culminating in long-term seizure susceptibility. We previously reported that an intracerebroventricular administration of ethacrynic acid (EA) to mice induced repeated tonic-clonic convulsions. We aimed in this seizure model to demonstrate molecular and cellular events leading to the seizure susceptibility, in relation to the expression of immediate early gene c-fos. Studies on the long-term expression of c-fos mRNA revealed that the expression was increased biphasically, with a transient increase at 60 min (early phase) and a prolonged increase on the 10-14th day (late phase) post-EA administration, most remarkably in dentate gyrus and pyriform cortex. The expression of NGF,a neurotrophic factor supposed to play a role in the reorganization of neural circuity, also showed biphasic increases with a close spatiotemporal correlation with c-fos expression. In addition, immuno-histochemical analysis displayd that the dendrites of parvalbumin (PARV) -positive cells, a subpopulation of GABAergic interneurons, were markedly decreased on the 7th day post-EA seizure and that their cell somata also decreased on 14th day. Furthermore, we examined the development of seizure susceptibity in EA-treated mice on the 14th day. Intraperitoneal injection with subconvulsive dose of kainic acid caused severe (stage 5) seizure in 77% of mice recovered from EA seizure with 70% mortality within 10 min. These findings suggest that the transient EA-induced seizures produce the development of long-term seizure susceptibility via prolonged increase in c-fos expression and subsequent increase in NGF mRNA expression. Also, it was supposed that the loss of PARV-positive cells which precede the late phase increase in c-fos expression play a causal role in the development.
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Research Products
(8 results)
