MicroRNA let-7c-5p protects against cerebral ischemia injury via mechanisms involving the inhibition of microglia activation.

Abstract

The present study was designed to reveal the potential role of let-7c-5p, a highly conserved miRNA in stroke. We found that the content of let-7c-5p was significantly decreased in the plasma of patients with ischemic stroke as well as in experimental animals. Moreover, we also observed a significant decrease of let-7c-5p in ipsilateral cortex and striatum in mice that were subjected to middle cerebral artery occlusion (MCAO) at 24h reperfusion. Overexpression of let-7c-5p via ICV injection decreased the infarction volume and attenuated the neurological deficits, and most interestingly, inhibited microglial activation. To further explore the mechanism, we checked let-7c-5p expression in BV2 cells and primary microglia in an OGD condition and in LPS-induced microglial activation. The results indicated that decreased let-7c-5p was evidenced in the activated microglia. Overexpression of let-7c-5p in BV2 cells remarkably inhibited the microglial activation. The inhibition of microglial activation by overexpression of let-7c-5p was also observed in mice with experimental stroke, which is in line with the decreased infarction volume and improved neurological deficits. We identified that let-7c-5p directly targeted to the 3'-untranslated region of the caspase 3 mRNA to reduce caspase 3 levels, which may underline the miRNA - modulated microglial activity. The present study revealed that suppression of microglia activation by let-7c-5p overexpression may be involved in the protection effects of ischemic damage. The mechanism may include the miRNA-mediated caspase 3 pathway.

• Authors: Jingshu Ni, Xiaoyu Wang, Shuangshuang Chen, Huihui Liu, Yun Wang, Xingshun Xu, Jian Cheng, Jia Jia, Xuechu Zhen
• Journal: Brain, behavior, and immunity (Brain Behav Immun) Vol. 49 Pg. 75-85 (Oct 2015) ISSN: 1090-2139 [Electronic] Netherlands
• PMID: 25934573 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• 3' Untranslated Regions
• Inflammation Mediators
• MicroRNAs
• Caspase 3

Topics

• 3' Untranslated Regions
• Aged
• Animals
• Brain Ischemia (blood)
• Caspase 3 (metabolism)
• Cerebral Cortex (metabolism)
• Corpus Striatum (metabolism)
• Disease Models, Animal
• Encephalitis (metabolism)
• Humans
• Inflammation Mediators (metabolism)
• Male
• Mice
• MicroRNAs (administration & dosage, blood, metabolism)
• Microglia (metabolism)
• Middle Aged
• Stroke (blood)