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Modulation of Brain Pathology by Enhancer RNAs in Cerebral Ischemia
Sunil Bhattarai1, Aparna Akella1, Atish Gandhi1
1Laboratory for Stroke Research and Noncoding RNA Biology, JFK Neuroscience Institute, Hackensack Meridian Health JFK University Medical Center, 65 James Street, Edison, NJ, 08820, USA.
Molecular Neurobiology
|November 17, 2020
Summary
This study reveals enhancer RNAs (eRNAs) play a neuroprotective role after stroke. Identifying stroke-induced eRNAs and their function in the brain offers new therapeutic targets for stroke recovery.
Area of Science:
- Neuroscience
- Molecular Biology
- Genomics
Background:
- Enhancer RNAs (eRNAs) are noncoding RNAs transcribed from enhancers.
- eRNAs regulate gene expression and influence cellular functions.
- The role of eRNAs in cerebral ischemia (stroke) remains largely unexplored.
Purpose of the Study:
- To identify and characterize stroke-induced eRNAs in the mouse cerebral cortex.
- To investigate the functional significance of these eRNAs in the context of cerebral ischemia.
- To explore potential sex-specific differences in eRNA expression following stroke.
Main Methods:
- Genome-wide H3K27ac ChIP-seq to identify enhancer elements.
- Genome-wide RNA-seq to detect and quantify eRNAs.
- Middle cerebral artery occlusion (MCAO) model of transient focal ischemia in mice.
- Knockdown of specific eRNAs to assess their functional impact.
Main Results:
- Identified 77 significantly upregulated eRNAs in stroke compared to sham conditions.
- 55 of these eRNAs were exclusively expressed in the stroke group.
- Knockdown of two stroke-induced eRNAs led to larger infarct volumes, indicating a neuroprotective role.
- Preliminary data suggest sex-dependent patterns of eRNA expression.
Conclusions:
- This is the first study to map the eRNA landscape in the post-stroke cortex.
- Specific stroke-induced eRNAs are involved in the neuroprotective response to cerebral ischemia.
- eRNAs represent potential therapeutic targets for mitigating stroke-induced brain damage.
- Sex-specific eRNA regulation may contribute to differential stroke outcomes between males and females.
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