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c-fos antisense oligonucleotide prevents delayed induction of hsp70 mRNA after soman-induced seizures
V Baille1, G Lallement, P Carpentier
1Centre de Recherches du Service de Santé des Armées, Unité de Neurotoxicologie, La Tronche, France.
Abstract:
Previous studies have shown the successive expression of c-fos and hsp70 genes, especially in the hippocampal formation, during soman-induced seizures. In order to detect a possible link between the induction of these two genes, antisense strategies have been used. First, the ability of unilateral intrahippocampal infusion of c-fos antisense oligonucleotides to inhibit ipsilateral, seizure-related, c-FOS-like immunoreactivity, was verified. Second, induction of hsp70 mRNA was investigated using in situ hybridization. Unilateral inhibition of c-fos induction clearly reduced levels of hsp70 mRNA in the c-fos antisense-infused hippocampus relative to the non-infused contralateral side. Infusion of c-fos sense probe or vehicle did not affect bsp70 mRNA induction. This study suggests a role of c-FOS in regulating bsp70 mRNA induction.
Insights
This study investigated the link between c-fos and hsp70 gene expression during seizures. Inhibiting c-fos gene induction reduced hsp70 mRNA levels, suggesting c-FOS regulates hsp70 mRNA induction in the hippocampus.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Soman-induced seizures trigger sequential expression of c-fos and hsp70 genes in the hippocampus.
- The precise relationship between c-fos and hsp70 gene induction remains unclear.
Purpose of the Study:
- To investigate the potential regulatory link between c-fos and hsp70 gene induction.
- To determine if c-FOS plays a role in the upregulation of hsp70 mRNA during seizures.
Main Methods:
- Utilized antisense oligonucleotide strategies for targeted gene inhibition.
- Administered c-fos antisense oligonucleotides unilaterally into the hippocampus.
- Assessed c-FOS-like immunoreactivity and hsp70 mRNA levels via in situ hybridization.
Main Results:
- Unilateral inhibition of c-fos induction significantly decreased hsp70 mRNA levels in the treated hippocampus compared to the contralateral side.
- Infusion of c-fos sense probe or vehicle did not alter hsp70 mRNA induction.
- Confirmed that c-fos antisense oligonucleotides effectively inhibited seizure-related c-FOS-like immunoreactivity.
Conclusions:
- c-FOS appears to play a regulatory role in the induction of hsp70 mRNA.
- The findings suggest a molecular pathway where c-fos influences hsp70 expression in the context of seizures.