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

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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.

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Acknowledgments

We would like to thank Dr. Youn-Bok Lee, Dr. Kate Whittington and Dr. Liang-Fong Wong for their help and advice during this project. This work was funded by University of Bristol funds to SK, grants to JBU from the Wellcome Trust and BBSRC. MPK held a BBSRC CASE studentship.

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Authors and Affiliations

  1. School of Clinical Sciences & School of Cellular and Molecular Medicine, Regenerative Medicine Laboratories, University Walk, Bristol, BS8 1TD, UK

    Matthew P . Keasey, Helen L. Scott, James B. Uney & Stephen Kelly

  2. Faculty of Life Sciences, University of Manchester, Manchester, UK

    Ioannis Bantounas

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  1. Matthew P . Keasey
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  2. Helen L. Scott
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  3. Ioannis Bantounas
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  4. James B. Uney
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Correspondence to James B. Uney or Stephen Kelly.

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Keasey, M.P..., Scott, H.L., Bantounas, I. et al. MiR-132 Is Upregulated by Ischemic Preconditioning of Cultured Hippocampal Neurons and Protects them from Subsequent OGD Toxicity. J Mol Neurosci 59, 404–410 (2016). https://doi.org/10.1007/s12031-016-0740-9

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  • DOI: https://doi.org/10.1007/s12031-016-0740-9

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