In vivo administration of c-Fos antisense oligonucleotides accelerates amygdala kindling.
Repeated subconvulsive electrical stimulation of the amygdala leads to generalized seizures and provides an experimental model of epileptogenesis. Following electrical kindling stimulation the expression of c-Fos is rapidly induced. To evaluate the role of FOS protein in epileptogenesis, we used an antisense oligonucleotide strategy designed to inhibit its expression in the brain. Experimental and control oligonucleotides were delivered directly into the amygdala just prior to electrical stimulation. Immunocytochemical analysis showed that the administration of c-Fos antisense (but not sense) oligonucleotides inhibited expression of FOS in the amygdala following electrical stimulation. Behaviorally, treatment with c-Fos antisense oligonucleotides significantly accelerated the development of fully kindled (stage V) seizures. These data suggest that the increased FOS expression following electrical stimulation may be part of a protective mechanism which acts to inhibit epileptogenesis in the amygdala.
Rocha
L
L
Instituto Mexicano de Psiquiatría, Mexico City, Mexico.
Kaufman
D L
DL
D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004827:Epilepsy / Q000503:physiopathology*; D007150:Immunohistochemistry; D007696:Kindling, Neurologic / Q000502:physiology*; D008297:Male; D009841:Oligonucleotides / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D013873:Thionucleotides / Q000494:pharmacology
D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D016760:Proto-Oncogene Proteins c-fos; D013873:Thionucleotides