Abstract
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 μl) 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 afterdischarge 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.
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