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Activation of Arc gene, a dendritic immediate early gene, by middle cerebral artery occlusion in rat brain
H Kunizuka1, H Kinouchi, S Arai
1Department of Neurosurgery, Akita University School of Medicine, Japan.
Abstract:
The effect of middle cerebral artery (MCA) occlusion on the activity-regulated cytoskeleton-associated protein (Arc) mRNA expression has been investigated using in situ hybridization. It was induced in the extensive regions of cerebral cortex, medial striatum, and distant areas such as the ipsilateral lateral septal nucleus, bilateral hippocampal formation and contralateral amygdala following MCA occlusion. In the hippocampal formation, it was induced in the granule cell layer and the stratum pyramidale at 1 h and in the molecular layer and in the stratum oriens and stratum radiatum bilaterally at 4 h. MK-801 pretreatment strongly attenuated the induction of Arc mRNA. The present results suggest that Arc may play an important role in the neuronal plasticity through NMDA activation following focal cerebral ischemia.
Insights
Middle cerebral artery (MCA) occlusion increases activity-regulated cytoskeleton-associated protein (Arc) mRNA in the brain. NMDA receptor activation is involved, suggesting Arc
Area of Science:
- Neuroscience
- Molecular Biology
- Cerebrovascular Research
Background:
- Focal cerebral ischemia, such as middle cerebral artery (MCA) occlusion, triggers complex molecular responses in the brain.
- Activity-regulated cytoskeleton-associated protein (Arc) is an immediate-early gene involved in synaptic plasticity.
Purpose of the Study:
- To investigate the effect of MCA occlusion on Arc mRNA expression in various brain regions.
- To explore the role of NMDA receptor activation in Arc induction following ischemic stroke.
Main Methods:
- In situ hybridization was used to detect Arc mRNA expression.
- Middle cerebral artery (MCA) occlusion was induced in a rodent model.
- MK-801, an NMDA receptor antagonist, was administered as a pretreatment.
Main Results:
- MCA occlusion led to widespread induction of Arc mRNA in the cerebral cortex, striatum, hippocampus, and amygdala.
- Arc mRNA induction in the hippocampus showed distinct temporal and spatial patterns.
- MK-801 pretreatment significantly reduced the induction of Arc mRNA.
Conclusions:
- Arc mRNA expression is upregulated in response to focal cerebral ischemia.
- NMDA receptor activation plays a crucial role in the induction of Arc following MCA occlusion.
- Arc may be involved in neuronal plasticity mechanisms activated during ischemic stroke.