Inhibition of miR-497 improves functional outcome after ischemic stroke by enhancing neuronal autophagy in young and aged rats. (July 2019)

• Record Type: Journal Article
• Authors: Chen, Xudong; Lin, Siyang; Gu, Lei; Zhu, Xiaohong; Zhang, Yinuo; Zhang, Hongxia; Shao, Bei; Zhuge, Qichuan; Jin, Kunlin
• Is Part Of: Neurochemistry international. Volume 127(2019)
• Page Start: 64
• Page End: 72
• Publication Date: 2019-07
• Subjects: Autophagy -- Ischemic stroke -- MiRNA -- Neuroprotection -- Aging -- miR-497; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2019.01.005
• Languages: English
• ISSNs: 0197-0186

Abstract

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. Highlights: The first study showing miR-479 improved functional outcome after ischemia by enhancing autophagy. Neuronal autophagy is beneficial for stroke in the early stage, and probably is a major part of survival mechanism of acute cerebral ischemia. MiR-497 affected on mitochondrion-targeted Bcl-2 and may directly act on LC3. MiR-497 inhibition-mediated neuroprotection is age-dependent, which is less effective in aged rats.