| Title |
Inhibition of the Epigenetic Regulator REST Ameliorates Ischemic Brain Injury
|
|---|---|
| Published in |
Molecular Neurobiology, July 2018
|
| DOI | 10.1007/s12035-018-1254-y |
| Pubmed ID | |
| Authors |
Kahlilia C. Morris-Blanco, TaeHee Kim, Mario J. Bertogliat, Suresh L. Mehta, Anil K. Chokkalla, Raghu Vemuganti |
| Abstract |
Cerebral ischemia is known to activate the repressor element-1 (RE1)-silencing transcription factor (REST) which silences neural genes via epigenetic remodeling and promotes neurodegeneration. We presently determined if REST inhibition derepresses target genes involved in synaptic plasticity and promotes functional outcome after experimental stroke. Following transient focal ischemia induced by middle cerebral artery occlusion (MCAO) in adult rats, REST expression was upregulated significantly from 12 h to 1 day of reperfusion compared to sham control. At 1 day of reperfusion, REST protein levels were increased and observed in the nuclei of neurons in the peri-infarct cortex. REST knockdown by intracerebral REST siRNA injection significantly reduced the post-ischemic expression of REST and increased the expression of several REST target genes, compared to control siRNA group. REST inhibition also decreased post-ischemic markers of apoptosis, reduced cortical infarct volume, and improved post-ischemic functional recovery on days 5 and 7 of reperfusion compared to the control siRNA group. REST knockdown resulted in a global increase in synaptic plasticity gene expression at 1 day of reperfusion compared to the control siRNA group and significantly increased several synaptic plasticity genes containing RE-1 sequences in their regulatory regions. These results demonstrate that direct inhibition of the epigenetic remodeler REST prevents secondary brain damage in the cortex and improves functional outcome potentially via de-repression of plasticity-related genes after stroke. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 26 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 4 | 15% |
| Student > Master | 3 | 12% |
| Student > Postgraduate | 3 | 12% |
| Student > Doctoral Student | 2 | 8% |
| Unspecified | 2 | 8% |
| Other | 5 | 19% |
| Unknown | 7 | 27% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 5 | 19% |
| Medicine and Dentistry | 4 | 15% |
| Agricultural and Biological Sciences | 3 | 12% |
| Unspecified | 2 | 8% |
| Biochemistry, Genetics and Molecular Biology | 2 | 8% |
| Other | 2 | 8% |
| Unknown | 8 | 31% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 July 2018.
All research outputs
#20,527,576
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Outputs from Molecular Neurobiology
#2,829
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Outputs of similar age
#288,123
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Outputs of similar age from Molecular Neurobiology
#118
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