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Acute effect of c-fos antisense oligodeoxynucleotide on hippocampal partial seizures elicited by electrical
H Katsumori1, K Hashimoto, S Tomitaka
1Division of Cortical Function Disorders, National Institute of Neuroscience, Tokyo, Japan. hkatsumo@ucla.edu
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 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.
Insights
Antisense oligodeoxynucleotides (ODNs) targeting c-fos mRNA reduced seizure duration in rats. This suggests c-fos plays a key role in hippocampal excitability and seizure expression.
Area of Science:
- Neuroscience
- Molecular Biology
Background:
- Hippocampal partial seizures are a significant neurological condition.
- The role of specific genes, like c-fos, in seizure pathogenesis requires further elucidation.
Purpose of the Study:
- To investigate the effect of antisense oligodeoxynucleotides (ODNs) targeting c-fos mRNA on hippocampal partial seizures in a rat model.
- To assess the impact of c-fos modulation on seizure parameters and gene expression.
Main Methods:
- Rats were administered antisense, sense, or scrambled control ODNs via lateral ventricular injections.
- Electrical stimulation was used to induce seizures and measure afterdischarge duration (ADD).
- c-Fos and Jun-B protein expression was analyzed using immunocytochemistry.
Main Results:
- Antisense ODNs significantly decreased ADD compared to control ODNs.
- Control ODNs did not alter seizure parameters.
- Antisense ODNs selectively inhibited contralateral c-Fos expression in dentate granule cells.
Conclusions:
- c-fos plays a critical role in hippocampal excitability and seizure expression.
- Targeting c-fos mRNA with antisense ODNs offers a potential therapeutic strategy for managing hippocampal partial seizures.