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MK-801, a non-competitive NMDA receptor antagonist, prevents postischemic decrease of inositol 1,4,5-trisphosphate
1Institute of Human Genetics and Department of Anatomy, Korea University College of Medicine, Seoul, South Korea. uhmcs@kuccnx.korea.ac.kr
Neuroscience Letters
|December 3, 1998
Summary
Transient brain ischemia decreases inositol 1,4,5-trisphosphate receptor (IP3R) mRNA expression. Pretreatment with MK-801, an N-methyl-D-aspartic acid (NMDA) receptor antagonist, prevented this change, suggesting a link between NMDA receptors and IP3R mRNA expression during ischemia.
Area of Science:
- Neuroscience
- Molecular Biology
- Ischemia Research
Background:
- Inositol 1,4,5-trisphosphate receptors (IP3Rs) are crucial for intracellular calcium signaling.
- Transient brain ischemia can lead to significant cellular damage and altered gene expression.
- N-methyl-D-aspartic acid (NMDA) receptors play a role in excitotoxicity during ischemic events.
Purpose of the Study:
- To investigate the changes in IP3R mRNA expression following transient brain ischemia in Mongolian gerbils.
- To determine the effect of the NMDA receptor antagonist MK-801 on IP3R mRNA expression during and after ischemia.
Main Methods:
- Transient focal cerebral ischemia was induced in Mongolian gerbils by ligating the left common carotid artery for 10 minutes.
- In situ hybridization was employed to analyze IP3R mRNA expression levels in brain tissue.
- MK-801 was administered intraperitoneally 30 minutes prior to the ischemic insult.
Main Results:
- Ischemia led to a significant decrease in IP3R mRNA expression in the dentate gyrus and hippocampus, observed from 90 minutes to 24 hours post-ischemia.
- Pretreatment with MK-801 effectively prevented the ischemia-induced downregulation of IP3R mRNA expression.
- These findings indicate a temporal correlation between reduced IP3R mRNA and the ischemic period.
Conclusions:
- Ischemia-induced changes in IP3R mRNA expression in the brain appear to be modulated by NMDA receptor activity.
- The results suggest a potential link between NMDA receptor signaling pathways and the regulation of IP3R expression during ischemic conditions.
- Targeting NMDA receptors may offer a therapeutic strategy to mitigate ischemia-related alterations in IP3R expression.