title: Inhibition of microRNA-181 reduces forebrain ischemia-induced neuronal loss.
abstract: MicroRNA (miRNA), miR-181a, is enriched in the brain, and inhibition of miR-181a reduced astrocyte death in vitro and infarct volume after stroke in vivo. This study investigated the role of miR-181a in neuronal injury in vitro and hippocampal neuronal loss in vivo after forebrain ischemia. miR-181a levels were altered by transfection with mimic or antagomir. N2a cells subjected to serum deprivation and oxidative stress showed less cell death when miR-181a was reduced and increased death when miR-181a increased; protection was associated with increased Bcl-2 protein. In contrast, transfected primary neurons did not show altered levels of cell death when miR-181a levels changed. Naive male rats and rats stereotactically infused with miR-181a antagomir or control were subjected to forebrain ischemia and cornus ammonis (CA)1 neuronal survival and protein levels were assessed. Forebrain ischemia increased miR-181a expression and decreased Bcl-2 protein in the hippocampal CA1 region. miR-181a antagomir reduced miR-181a levels, reduced CA1 neuronal loss, increased Bcl-2 protein, and significantly prevented the decrease of glutamate transporter 1. Thus, miR-181a antagomir reduced evidence of astrocyte dysfunction and increased CA1 neuronal survival. miR-181a inhibition is thus a potential target in the setting of forebrain or global cerebral ischemia as well as focal ischemia.
authors.affiliation: 1] Department of Anesthesia, Stanford University School of Medicine, Stanford, California, USA [2] Department of Emergency Medicine, Chonnam National University School of Medicine, Gwangju, South Korea.
authors.forename: Jeong-mi
authors.initials: JM
authors.lastname: Moon
authors.forename: Lijun
authors.initials: L
authors.lastname: Xu
authors.forename: Rona G
authors.initials: RG
authors.lastname: Giffard
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002545:Brain Ischemia / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D002460:Cell Line; D002478:Cells, Cultured; D015536:Down-Regulation; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D009841:Oligonucleotides / Q000235:genetics / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
chemical_list: D027342:Excitatory Amino Acid Transporter 2; C581717:MIRN181 microRNA, rat; D035683:MicroRNAs; D009841:Oligonucleotides; D019253:Proto-Oncogene Proteins c-bcl-2; C529100:mirn181 microRNA, mouse