Inhibition of miRNA-27b enhances neurogenesis via AMPK activation in a mouse ischemic stroke model.

Stroke is a leading cause of death and disability, but treatment options remain limited. Recent studies have suggested that cerebral ischemia-induced neurogenesis plays a vital role in post-stroke repair. Overactivation of AMP-activated protein kinase (AMPK), a master sensor of energy balance, has been reported to exacerbate neuron apoptosis, but the role of chronic AMPK stimulus in post-stroke recovery remains unclear. MicroRNAs have emerged as regulators of neurogenesis and have been reported to be involved in neurological function. In this study, we verified that miR-27b directly targets AMPK and inhibits AMPK expression. In cultured neural stem cells, miR-27b inhibitor improved proliferation and differentiation via the AMPK signaling pathway, but did not have an obvious effect on cell viability under oxygen and glucose deprivation conditions. In a mouse middle cerebral artery occlusion model, administration of miR-27b inhibitor significantly enhanced behavioral function recovery and spatial memory. Up-regulation of neurogenesis was observed both in the subventricular zone and in the hippocampal dentate gyrus. Collectively, our data suggest that miR-27b inhibition promotes recovery after ischemic stroke by regulating AMPK activity. These findings may facilitate the development of novel therapeutic strategies for stroke.