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Astrocyte-enriched miR-29a targets PUMA and reduces neuronal vulnerability to forebrain ischemia

Ouyang, Yi‐Bing, Xu, Lijun, Lu, Yu, Sun, Xiaoyun, Yue, Sibiao, Xiong, Xiao‐Xing, Giffard, Rona G.·2013·Glia
DOI 10.1002/glia.22556PMC PMC3810393
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Abstract

Following transient forebrain ischemia, astrocytes play a key role in determining whether or not neurons in the hippocampal CA1 sector go on to die in a delayed fashion. MicroRNAs (miRNAs) are a novel class of RNAs that control gene expression at the post‐transcriptional level and the miR‐29 family is highly expressed in astrocytes. In this study we assessed levels of miR‐29 in hippocampus following forebrain ischemia and found that after transient forebrain ischemia and short periods of reperfusion, miR‐29a significantly increased in the resistant dentate gyrus, but decreased in the vulnerable CA1 region of the hippocampus. We demonstrate that miR‐29a targets BH3‐only proapoptotic BCL2 family member PUMA by luciferase reporter assay and by Western blot. Comparing primary neuron and astrocyte cultures, and postnatal brain, we verified the strongly astrocytic expression of miR‐29a. We further found that miR‐29a mimic protects and miR‐29a inhibitor aggravates cell injury and mitochondrial function after ischemia‐like stresses in vitro. Lastly, by overexpressing and reducing miR‐29a we demonstrate the protective effect of miR‐29a on CA1 delayed neuronal death after forebrain ischemia. Our data suggest that by targeting a pro‐apoptotic BCL2 family member, increasing levels of miR‐29a might emerge as a strategy for protection against ischemia‐reperfusion injury. GLIA 2013;61:1784–1794

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Authors
Ouyang, Y., Xu, L., Lu, Y., Sun, X., Yue, S., Xiong, X., & Giffard, R. G.
Affiliations
  • Department of Anesthesia Stanford University School of Medicine Stanford California
  • Department of Biology Johns Hopkins University Baltimore Maryland
Venue
Glia
Publisher
Wiley
Published
2013-08-30
Volume
61
Issue
11
Pages
1784-1794
ISSN
  • 0894-1491
  • 1098-1136
DOI
10.1002/glia.22556
PMC
PMC3810393
Cited by
139
References
1
Language
en
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Funders
NIH (GM049831, NS053898, NS080177)

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