Inhibition of miR-497 improves functional outcome after ischemic stroke by enhancing neuronal autophagy in young and aged rats.

Abstract

Over the years miR-497 has been found to play a vital role in the pathogenesis of neurological diseases, including ischemic stroke. However, its underlying mechanism remains largely unexplored. Here, we used miR-497 agomir (miR-497 agonist), miR-497 antagomir (miR-497 inhibitor) and 3-MA (autophagy inhibitor) to treat ischemic rats (n = 10-12 per group) induced by permanent distal middle cerebral artery occlusion (dMCAO), followed the functional outcome assessment 24 h after dMCAO. We found that treatment of miR-497 antagomir, but not miR-497 angomir, reduced the infarct volume and improved neurological deficits after ischemic stroke, along with upregulation of the autophagy-related protein LC3 expression (mean ± SEM,p < 0.05). While the ischemic rats treated with 3-MA exhibited inhibition of autophagy, which in turn abolished functional recovery as observed in miR-497 antagomir-treated group (p < 0.05). Interestingly, the role of miR-497 in functional recovery in aged ischemic rats was less effective, compared to young adult ischemic rats (p < 0.05). Our data suggest that inhibition of miR-497 could protect cerebral ischemic injury by enhancing autophagy and also age-dependent.

• Authors: Xudong Chen, Siyang Lin, Lei Gu, Xiaohong Zhu, Yinuo Zhang, Hongxia Zhang, Bei Shao, Qichuan Zhuge, Kunlin Jin
• Journal: Neurochemistry international (Neurochem Int) Vol. 127 Pg. 64-72 (07 2019) ISSN: 1872-9754 [Electronic] England
• PMID: 30654114 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• MIRN497 microRNA, rat
• MicroRNAs

Topics

• Aging
• Animals
• Autophagy (genetics)
• Brain Ischemia (genetics, metabolism, therapy)
• Disease Models, Animal
• Infarction, Middle Cerebral Artery (genetics, pathology)
• Male
• MicroRNAs (antagonists & inhibitors, genetics)
• Neurons (drug effects, metabolism)
• Rats, Sprague-Dawley
• Stroke (genetics, metabolism, therapy)