title: MiR-132 Is Upregulated by Ischemic Preconditioning of Cultured Hippocampal Neurons and Protects them from Subsequent OGD Toxicity.
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.
authors.affiliation: School of Clinical Sciences & School of Cellular and Molecular Medicine, Regenerative Medicine Laboratories, University Walk, Bristol, BS8 1TD, UK.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Keasey
authors.affiliation: School of Clinical Sciences & School of Cellular and Molecular Medicine, Regenerative Medicine Laboratories, University Walk, Bristol, BS8 1TD, UK.
authors.forename: Helen L
authors.initials: HL
authors.lastname: Scott
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Bantounas
authors.affiliation: School of Clinical Sciences & School of Cellular and Molecular Medicine, Regenerative Medicine Laboratories, University Walk, Bristol, BS8 1TD, UK. james.uney@bristol.ac.uk.
authors.forename: James B
authors.initials: JB
authors.lastname: Uney
authors.affiliation: School of Clinical Sciences & School of Cellular and Molecular Medicine, Regenerative Medicine Laboratories, University Walk, Bristol, BS8 1TD, UK. ischemia@gmail.com.
authors.forename: Stephen
authors.initials: S
authors.lastname: Kelly
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005947:Glucose / Q000172:deficiency* / Q000378:metabolism; D006624:Hippocampus / Q000098:blood supply / Q000166:cytology; D006861:Hydrogen Peroxide / Q000633:toxicity; D019194:Ischemic Preconditioning; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016202:N-Methylaspartate / Q000633:toxicity; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C548821:MIRN132 microRNA, rat; D035683:MicroRNAs; D016202:N-Methylaspartate; D006861:Hydrogen Peroxide; D005947:Glucose; D010100:Oxygen
keywords: MicroRNA; Neuron; Neuroprotection; Oxygen-glucose deprivation; Preconditioning; miR-132