MiR-132 Is Upregulated by Ischemic Preconditioning of Cultured Hippocampal Neurons and Protects them from Subsequent OGD Toxicity

Matthew P. Keasey, Helen L. Scott, Ioannis Bantounas, James B. Uney*, Stephen Kelly

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

17 Citations (Scopus)

Abstract

We explored the response of a panel of selected microRNAs (miRNAs) in neuroprotection produced by ischemic preconditioning. Hippocampal neuronal cultures were exposed to a 30-min oxygen–glucose deprivation (OGD). In our hands, this duration of OGD does not result in neuronal loss in vitro but significantly reduces neuronal death from a subsequent ‘lethal’ OGD insult. RT-qPCR was used to determine the expression of 16 miRNAs of interest at 1 and 24-h post-OGD. One miRNA (miR-98) was significantly decreased at 1-h post-OGD. Ten miRNAs (miR-9, miR-21, miR-29b, miR-30e, miR-101a, miR-101b, miR-124a, miR-132, miR-153, miR-204) were increased significantly at 24-h post-OGD. No miRNAs were decreased at 24-h. The increases observed in the 24-h group suggested that these miRNAs might play a role in preconditioning-induced neuroprotection. We selected the widely studied miR-132, a brain enriched, CREB regulated miRNA, to explore its role in simulated ischemic insults. We found that hippocampal neurons transduced with lentiviral vectors expressing miR-132 were protected from OGD and NMDA treatment, but not hydrogen peroxide. These findings add to the growing literature that targeting neuroprotective pathways controlled by miRNAs may represent a therapeutic strategy for the treatment of ischemic brain injury.
Original languageEnglish
Pages (from-to)404-410
Number of pages7
JournalJournal of Molecular Neuroscience
Volume59
Issue number3
Early online date13 Apr 2016
DOIs
Publication statusPublished - Jul 2016

Keywords

  • MicroRNA
  • miR-132
  • Neuron
  • Neuroprotection
  • Oxygen-glucose deprivation
  • Preconditioning

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