Perforant path stimulation differentially alters prodynorphin mRNA and proenkephalin mRNA levels in the entorhinal cortex-hippocampal region
Related Experiment Videos
C W Xie1, C L Mitchell, J S Hong
1Laboratory of Molecular and Integrative Neuroscience, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Abstract:
The regulatory effect of the perforant path on opioid gene expression in the entorhinal cortex-hippocampal region was investigated. The left perforant path was electrically stimulated at the angular bundle under conditions which elicit wet dog shakes but no motor seizures in rats. Animals were given either an acute stimulation composed of several consecutive stimulation trials, or daily stimulations with a single trial every day for 6 days. Rats were then sacrificed at 24 h or 6 days after the last trial. The amounts of prodynorphin mRNA (DYN mRNA) and proenkephalin A mRNA (EK mRNA) in the hippocampus and entorhinal cortex were measured by RNA blot analysis. Dynorphin A(1-8) and [Met5]enkephalin immunoreactivities were determined by radioimmunoassay. A decrease in DYN mRNA level of approximately 50-80% was found on both sides of the hippocampus 24 h after both acute and daily stimulation. Hippocampal dynorphin A(1-8) immunoreactivity was also reduced at 24 h, and persisted for at least 6 days. In contrast, bilateral increases in EK mRNA level were observed in the hippocampus (54-101%) and entorhinal cortex (97-165%) 24 h after the acute stimulation. Also, [Met5]enkephalin immunoreactivity in the hippocampus tended to be increased at this time. These results indicate that activation of the perforant path inhibits the gene expression of prodynorphin, but enhances that of proenkephalin in the entorhinal cortex-hippocampal region.
Insights
Electrical stimulation of the perforant path in rats altered opioid gene expression. Prodynorphin mRNA decreased, while proenkephalin A mRNA increased in the hippocampus and entorhinal cortex.
Area of Science:
- Neuroscience
- Molecular Biology
- Neuropharmacology
Background:
- The entorhinal cortex-hippocampal region is crucial for memory and emotion.
- Opioid peptides, like dynorphin and enkephalin, play significant roles in neuronal function.
- The perforant path is a major input to the hippocampus, influencing its activity.
Purpose of the Study:
- To investigate the regulatory effects of perforant path activation on opioid gene expression.
- To examine changes in prodynorphin mRNA (DYN mRNA) and proenkephalin A mRNA (EK mRNA) levels.
- To assess the impact on dynorphin A(1-8) and [Met5]enkephalin immunoreactivity.
Main Methods:
- Electrical stimulation of the left perforant path in rats.
- Acute and daily stimulation protocols were employed.
- RNA blot analysis and radioimmunoassay were used to quantify mRNA and peptide levels.
Main Results:
- Perforant path stimulation significantly decreased DYN mRNA levels (50-80%) in the hippocampus.
- Hippocampal dynorphin A(1-8) immunoreactivity was reduced and persisted for at least 6 days.
- Bilateral increases in EK mRNA levels were observed in the hippocampus (54-101%) and entorhinal cortex (97-165%) following acute stimulation.
Conclusions:
- Activation of the perforant path inhibits prodynorphin gene expression in the entorhinal cortex-hippocampal region.
- Conversely, perforant path activation enhances proenkephalin gene expression in this same region.
- These findings highlight differential regulation of opioid systems by perforant path input.