MicroRNA-223 is neuroprotective by targeting glutamate receptors

Research output: Contribution to journalArticle

Abstract

Stroke is a major cause of mortality and morbidity worldwide. Extracellular glutamate accumulation leading to overstimulation of the ionotropic glutamate receptors mediates neuronal injury in stroke and in neurodegenerative disorders. Here we show that miR-223 controls the response to neuronal injury by regulating the functional expression of the glutamate receptor subunits GluR2 and NR2B in brain. Overexpression of miR-223 lowers the levels of GluR2 and NR2B by targeting 3′-UTR target sites (TSs) in GluR2 and NR2B, inhibits NMDA-induced calcium influx in hippocampal neurons, and protects the brain from neuronal cell death following transient global ischemia and excitotoxic injury. MiR-223 deficiency results in higher levels of NR2B and GluR2, enhanced NMDA-induced calcium influx, and increased miniature excitatory postsynaptic currents in hippocampal neurons. In addition, the absence of MiR-223 leads to contextual, but not cued memory deficits and increased neuronal cell death following transient global ischemia and excitotoxicity. These data identify miR-223 as a major regulator of the expression of GluR2 and NR2B, and suggest a therapeutic role for miR-223 in stroke and other excitotoxic neuronal disorders.

Original languageEnglish (US)
Pages (from-to)18962-18967
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number46
DOIs
StatePublished - Nov 13 2012

Fingerprint

Glutamate Receptors
MicroRNAs
Stroke
N-Methylaspartate
Wounds and Injuries
Cell Death
Ischemia
Calcium
Ionotropic Glutamate Receptors
Neurons
Excitatory Postsynaptic Potentials
Memory Disorders
Brain
3' Untranslated Regions
Neurodegenerative Diseases
Glutamic Acid
Morbidity
Mortality
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

@article{6e0e7c26dc844e3e8887c8ca9803c6a2,
title = "MicroRNA-223 is neuroprotective by targeting glutamate receptors",
abstract = "Stroke is a major cause of mortality and morbidity worldwide. Extracellular glutamate accumulation leading to overstimulation of the ionotropic glutamate receptors mediates neuronal injury in stroke and in neurodegenerative disorders. Here we show that miR-223 controls the response to neuronal injury by regulating the functional expression of the glutamate receptor subunits GluR2 and NR2B in brain. Overexpression of miR-223 lowers the levels of GluR2 and NR2B by targeting 3′-UTR target sites (TSs) in GluR2 and NR2B, inhibits NMDA-induced calcium influx in hippocampal neurons, and protects the brain from neuronal cell death following transient global ischemia and excitotoxic injury. MiR-223 deficiency results in higher levels of NR2B and GluR2, enhanced NMDA-induced calcium influx, and increased miniature excitatory postsynaptic currents in hippocampal neurons. In addition, the absence of MiR-223 leads to contextual, but not cued memory deficits and increased neuronal cell death following transient global ischemia and excitotoxicity. These data identify miR-223 as a major regulator of the expression of GluR2 and NR2B, and suggest a therapeutic role for miR-223 in stroke and other excitotoxic neuronal disorders.",
author = "Maged Harraz and Stephen Eacker and Xueqing Wang and Dawson, {Ted M} and Valina Dawson",
year = "2012",
month = "11",
day = "13",
doi = "10.1073/pnas.1121288109",
language = "English (US)",
volume = "109",
pages = "18962--18967",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "46",

}

TY - JOUR

T1 - MicroRNA-223 is neuroprotective by targeting glutamate receptors

AU - Harraz, Maged

AU - Eacker, Stephen

AU - Wang, Xueqing

AU - Dawson, Ted M

AU - Dawson, Valina

PY - 2012/11/13

Y1 - 2012/11/13

N2 - Stroke is a major cause of mortality and morbidity worldwide. Extracellular glutamate accumulation leading to overstimulation of the ionotropic glutamate receptors mediates neuronal injury in stroke and in neurodegenerative disorders. Here we show that miR-223 controls the response to neuronal injury by regulating the functional expression of the glutamate receptor subunits GluR2 and NR2B in brain. Overexpression of miR-223 lowers the levels of GluR2 and NR2B by targeting 3′-UTR target sites (TSs) in GluR2 and NR2B, inhibits NMDA-induced calcium influx in hippocampal neurons, and protects the brain from neuronal cell death following transient global ischemia and excitotoxic injury. MiR-223 deficiency results in higher levels of NR2B and GluR2, enhanced NMDA-induced calcium influx, and increased miniature excitatory postsynaptic currents in hippocampal neurons. In addition, the absence of MiR-223 leads to contextual, but not cued memory deficits and increased neuronal cell death following transient global ischemia and excitotoxicity. These data identify miR-223 as a major regulator of the expression of GluR2 and NR2B, and suggest a therapeutic role for miR-223 in stroke and other excitotoxic neuronal disorders.

AB - Stroke is a major cause of mortality and morbidity worldwide. Extracellular glutamate accumulation leading to overstimulation of the ionotropic glutamate receptors mediates neuronal injury in stroke and in neurodegenerative disorders. Here we show that miR-223 controls the response to neuronal injury by regulating the functional expression of the glutamate receptor subunits GluR2 and NR2B in brain. Overexpression of miR-223 lowers the levels of GluR2 and NR2B by targeting 3′-UTR target sites (TSs) in GluR2 and NR2B, inhibits NMDA-induced calcium influx in hippocampal neurons, and protects the brain from neuronal cell death following transient global ischemia and excitotoxic injury. MiR-223 deficiency results in higher levels of NR2B and GluR2, enhanced NMDA-induced calcium influx, and increased miniature excitatory postsynaptic currents in hippocampal neurons. In addition, the absence of MiR-223 leads to contextual, but not cued memory deficits and increased neuronal cell death following transient global ischemia and excitotoxicity. These data identify miR-223 as a major regulator of the expression of GluR2 and NR2B, and suggest a therapeutic role for miR-223 in stroke and other excitotoxic neuronal disorders.

UR - http://www.scopus.com/inward/record.url?scp=84869205438&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84869205438&partnerID=8YFLogxK

U2 - 10.1073/pnas.1121288109

DO - 10.1073/pnas.1121288109

M3 - Article

C2 - 23112146

AN - SCOPUS:84869205438

VL - 109

SP - 18962

EP - 18967

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 46

ER -