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Published on: July 23, 2012
MicroRNA-124 protects neurons against apoptosis in cerebral ischemic stroke
1Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China.
Aims:
To explore the role and underlying mechanism of miR-124 in stroke.
Methods:
miR-124 expression was determined by real-time PCR. The effect of miR-124 on infarct area was assessed in middle cerebral artery occlusion (MCAO) mice. The influence of miR-124 on oxygen and glucose deprivation (OGD) induced neuron apoptosis and death was examined by immunofluorescence. The effect of miR-124 on apoptosis-related proteins was determined by Western blot.
Results:
The level of miR-124 is significantly increased in ischemic penumbra as compared with that in nonischemic area of MACO mice. Brain tissue of stroke-prone spontaneously hypertensive rats (SHR-SP) also showed higher level of miR-124 as compared with that of spontaneously hypertensive rats (SHR). Consistently, OGD treatment obviously increased miR-124 level in primary neurons. In vivo, miR-124 overexpression significantly decreased, while miR-124 knockdown significantly increased, the infarct area of MCAO mice. In vitro, gain or loss of miR-124 function resulted in reduced or increased neuron apoptosis and death induced by OGD, and increased or reduced antiapoptosis protein, Bcl-2 and Bcl-xl, respectively.
Conclusions:
miR-124 plays a neurons-protective role via apoptosis-inhibiting pathway in ischemic stroke.
Insights
MicroRNA-124 (miR-124) is elevated in ischemic stroke and protects neurons by inhibiting apoptosis. This finding offers a potential therapeutic target for stroke treatment.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Stroke is a leading cause of death and disability worldwide.
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression.
- Dysregulation of miRNAs has been implicated in various diseases, including stroke.
Purpose of the Study:
- To investigate the role and mechanism of miR-124 in ischemic stroke.
- To determine the effect of miR-124 on neuronal apoptosis and infarct size in stroke models.
Main Methods:
- Real-time PCR to quantify miR-124 expression.
- Middle cerebral artery occlusion (MCAO) mouse model for in vivo studies.
- Oxygen and glucose deprivation (OGD) in primary neurons for in vitro studies.
- Immunofluorescence and Western blot to assess apoptosis and related proteins.
Main Results:
- miR-124 levels were significantly increased in the ischemic penumbra of MCAO mice and in OGD-treated neurons.
- Overexpression of miR-124 reduced infarct size in MCAO mice, while knockdown increased it.
- miR-124 inhibited OGD-induced neuron apoptosis and modulated the expression of anti-apoptotic proteins Bcl-2 and Bcl-xl.
Conclusions:
- miR-124 exerts a neuroprotective effect in ischemic stroke.
- This protection is mediated through the inhibition of neuronal apoptosis.
- miR-124 represents a potential therapeutic target for stroke intervention.
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