Continuous administration of antisense oligonucleotides to c-fos reduced the development of seizure susceptibility after ethacrynic acid-induced seizure in mice.
We previously demonstrated that seizure susceptibility developed by the 14th day post-ethacrynic acid (EA)-induced seizure in mice, with a prolonged increase in the expression of c-fos mRNA in the brain during days 10-14. To examine whether such c-fos increase contributes to the development of seizure susceptibility, we administered antisense oligodeoxynucleotide to c-fos by continuous infusion into the lateral ventricle of mice that had shown a moderate stage of EA seizure, and evaluated the seizure susceptibility to kainic acid (10 mg/kg) on the 14th day. Antisense-infused mice displayed significant reduction of the c-Fos level in the hippocampus and cerebral cortex on the 7th and 14th days, and a significant decrease in seizure severity. These findings suggest that the prolonged increase in c-fos expression after EA seizure may lead to the development of seizure susceptibility.
Suzukawa
Junko
J
Department of Pharmacology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka 570-8506, Japan.
Omori
Kyoko
K
Yang
Li
L
Inagaki
Chiyoko
C
D000818:Animals; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004347:Drug Interactions / Q000502:physiology; D004827:Epilepsy / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D004976:Ethacrynic Acid / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D016376:Oligonucleotides, Antisense; D016760:Proto-Oncogene Proteins c-fos; D004976:Ethacrynic Acid; D007608:Kainic Acid