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MiR‐223 is neuroprotective by targeting the glutamate receptor
Author(s) -
Harraz Maged,
Eacker Stephen,
Dawson Ted,
Dawson Valina
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.650.12
Subject(s) - neuroprotection , glutamate receptor , pharmacology , chemistry , neuroscience , receptor , medicine , biology
MicroRNAs are short non‐coding RNA molecules that inhibit protein expression by complementary binding to the 3′UTR of their target mRNAs. We and others identified the expression of miR‐223 in the nervous system, but its CNS function remains unexplored. Recent studies demonstrate early up‐regulation of miR‐223 in the brain following ischemic preconditioning in vivo. These findings led us to hypothesize that miR‐223 plays a neuroprotective role. To test this hypothesis, we investigated delayed hippocampal neuronal death in miR‐223 knockout (KO) mice undergoing transient global cerebral ischemia (TGCI). We observed loss of spatial memory and enhanced hippocampal CA1 region neuronal death in miR‐223 (KO) mice compared to their wild type littermates following TGCI. Using bioinformatic microRNA target prediction algorithms, we identified subtypes of the glutamate receptor as candidate miR‐223 targets. We confirmed these findings using western blots; in vitro calcium mobilization assays, 3′UTR luciferase assays and NMDA induced neuronal injury in vivo. Our findings demonstrate that miR‐223 is a neuroprotective microRNA and suggest a therapeutic role in stroke and other excitotoxic neurodegenerative disorders. This work was supported by NIH 2P50DA000266. Maged Harraz was supported by MSCRF PDF # 104278.