Acute effect of c-fos antisense oligodeoxynucleotide on hippocampal partial seizures elicited by electrical stimulation in rats.
We examined the effects of antisense oligodeoxynucleotides (ODNs) to c-fos mRNA on hippocampal partial seizures in rats. As control, sense and scrambled control ODNs were also tested. Each ODN (10 nmol/10 microliters) was injected into the lateral ventricles for 2 consecutive days. Fifteen hours after the last injection, electrical stimulation was delivered to assess the effects on after discharge threshold and afterdischarge duration (ADD). One hour after seizures, c-Fos and Jun-B immunocytochemistries were performed. Antisense ODNs significantly decreased ADD and control ODNs failed to change any parameters. In the antisense ODNs group, c-Fos expression occurred ipsilateral to the stimulation site in dentate granule cells, while Jun-B expression was seen bilaterally. In the majority of control ODNs animals, c-Fos and Jun-B expression in dentate granule cells occurred bilaterally. These findings suggest that the injection of antisense ODNs selectively inhibit contralateral c-Fos expression and that c-fos plays a key role in hippocampal excitability and seizure expression during hippocampal partial seizures.
Katsumori
H
H
Division of Cortical Function Disorders, National Institute of Neuroscience, Tokyo, Japan. hkatsumo@ucla.edu
Hashimoto
K
K
Tomitaka
S
S
Osawa
M
M
Minabe
Y
Y
D000818:Animals; D004558:Electric Stimulation; D004828:Epilepsies, Partial / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D016376:Oligonucleotides, Antisense; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger