Long-lasting c-fos and NGF mRNA expressions and loss of perikaryal parvalbumin immunoreactivity in the development of epileptogenesis after ethacrynic acid-induced seizure
Autor: | Junko Suzukawa, Gaku Okugawa, Yoshito Fujiseki, Claus W. Heizmann, Chiyoko Inagaki, Kyoko Omori |
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Rok vydání: | 1999 |
Předmět: |
Male
Kainic acid medicine.medical_specialty Time Factors Glutamate decarboxylase Convulsants Epileptogenesis c-Fos Mice chemistry.chemical_compound Epilepsy Interneurons Internal medicine medicine Animals Tissue Distribution Nerve Growth Factors RNA Messenger Molecular Biology biology General Neuroscience Neural Inhibition medicine.disease Immunohistochemistry Ethacrynic Acid Parvalbumins Nerve growth factor Endocrinology nervous system chemistry biology.protein Disease Susceptibility Neurology (clinical) Excitatory Amino Acid Antagonists Proto-Oncogene Proteins c-fos Immediate early gene Parvalbumin Developmental Biology |
Zdroj: | Brain Research. 834:89-102 |
ISSN: | 0006-8993 |
DOI: | 10.1016/s0006-8993(99)01554-1 |
Popis: | A single cerebroventricular injection of ethacrynic acid (EA), a Cl(-)-ATPase inhibitor, induces generalized tonic-clonic convulsions in mice. To clarify whether such convulsive stimulus triggers a long-lasting rearrangement of the neural circuitry culminating in seizure susceptibility, we examined molecular, cellular and behavioral changes following the EA-induced seizure. The expression of immediate early gene c-fos mRNA as an index for cellular activation increased biphasically, with an early transient increase at 60 min and a late prolonged increase on the 10th to 14th day post-EA administration, most remarkably in the hippocampus and pyriform cortex. On the 14th day post-EA seizure, subconvulsive dose of kainic acid (5-17.5 mg/kg) caused severe (stage 5) seizure in 77% of the mice, with 70% mortality. In addition, the expression of nerve growth factor (NGF) also showed biphasic increases with close spatiotemporal correlation with c-fos expression. Moreover, the number of cell somata and the density of axon fibers of parvalbumin (PARV)-positive cells, a subpopulation of GABAergic interneurons, decreased in area dentata, CA1 and CA3 on the 7th and 14th day post-EA seizure. In area dentata and CA1, the density of glutamic acid decarboxylase (GAD)-positive cells also decreased on the 14th day. Thus, the transient EA-induced seizures appear to develop seizure susceptibility by causing damage of a subpopulation of inhibitory interneurons along with increases in the expression of c-fos and NGF in limbic structures. |
Databáze: | OpenAIRE |
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