MicroRNA 103‐1 exerts a neuroprotective effect in stroke by enhancing ncx1 expression in the brain (654.1)

Abstract

Background and purpose: MicroRNAs (miRNA) are single‐stranded short RNA molecules that regulate gene expression by either degradation or translational repression of mRNA. Recent studies showed that cerebral ischemia significantly alter cerebral miRNA profiles, mediating profound effect on the disease outcome. In that scenario the Na+/Ca2+ exchanger, by mediating Ca2+ and Na+ fluxes in a bidirectional way across the synaptic plasma membrane, may play a pivotal role in the events leading to anoxic damage. The objective of this study was to set up a valid therapeutical strategy able to contrast the role of specific miRNAs that downregulate NCX expression under experimental conditions mimicking stroke.Methods: NCX protein expression was evaluated after miRNA and atimiRNA cell trasfection. AntimiRNA 103‐1 was intracerebroventricularly administered in ischemic rat to prevent mir‐103‐1 detrimental action on NCX1.Results: NCX1 physiological expression was dramatically reduced when cells were treated with mir‐103‐1. Conversely, the in vivo approach showed that antimiRNA‐103‐1 protected from brain ischemia by up‐regulating the neurobeneficial protein NCX1.Conclusions: The present findings support the idea that blocking mir‐103‐1 by microRNA inhibitors is a reasonable strategy to stop neurodetrimental downregulation of NCX occurring during ischemic conditions.