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In vivo administration of c-Fos antisense oligonucleotides accelerates amygdala kindling
1Instituto Mexicano de Psiquiatría, Mexico City, Mexico.
Abstract:
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.
Insights
Inhibiting FOS protein expression in the amygdala accelerated seizure development in an epilepsy model. This suggests that increased FOS expression acts as a protective mechanism against epileptogenesis.
Area of Science:
- Neuroscience
- Epilepsy Research
- Molecular Biology
Background:
- Electrical kindling of the amygdala serves as an experimental model for epileptogenesis.
- Subconvulsive electrical stimulation of the amygdala can induce generalized seizures.
- The protein FOS (also known as FOS) is rapidly expressed following electrical kindling stimulation.
Purpose of the Study:
- To investigate the role of FOS protein in the development of epilepsy.
- To determine if inhibiting FOS expression affects seizure progression.
Main Methods:
- An antisense oligonucleotide strategy was employed to inhibit FOS expression in the amygdala.
- Oligonucleotides were delivered directly into the amygdala prior to electrical stimulation.
- Immunocytochemistry was used to confirm FOS expression inhibition.
- Behavioral analysis assessed seizure development and severity.
Main Results:
- Administration of c-Fos antisense oligonucleotides successfully inhibited FOS protein expression in the amygdala.
- Control (sense) oligonucleotides did not inhibit FOS expression.
- Treatment with c-Fos antisense oligonucleotides significantly accelerated the development of stage V seizures.
Conclusions:
- Increased FOS expression following electrical stimulation may represent a protective mechanism.
- This protective mechanism appears to inhibit the progression of epileptogenesis in the amygdala.