Induction of miR-155 after brain injury promotes type 1 interferon and has a neuroprotective effect

Emily B. Harrison, Katy Emanuel, Benjamin G. Lamberty, Brenda M. Morsey, Min Li, Matthew L. Kelso, Sowmya V Yelamanchili, Howard S Fox

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Traumatic brain injury (TBI) produces profound and lasting neuroinflammation that has both beneficial and detrimental effects. Recent evidence has implicated microRNAs (miRNAs) in the regulation of inflammation both in the periphery and the CNS. We examined the expression of inflammation associated miRNAs in the context of TBI using a mouse controlled cortical impact (CCI) model and found increased levels of miR-21, miR-223 and miR-155 in the hippocampus after CCI. The expression of miR-155 was elevated 9-fold after CCI, an increase confirmed by in situ hybridization (ISH). Interestingly, expression of miR-155 was largely found in neuronal nuclei as evidenced by co-localization with DAPI in MAP2 positive neurons. In miR-155 knock out (KO) mice expression of type I interferons IFNα and IFNβ, as well as IFN regulatory factor 1 and IFN-induced chemokine CXCL10 was decreased after TBI relative to wild type (WT) mice. Unexpectedly, miR-155 KO mice had increased levels of microglial marker Iba1 and increased neuronal degeneration as measured by fluoro-jade C (FJC) staining, suggesting a neuroprotective role for miR-155 in the context of TBI. This work demonstrates a role for miR-155 in regulation of the IFN response and neurodegeneration in the aftermath of TBI. While the presence of neuronal nuclear miRNAs has been described previously, their importance in disease states is relatively unknown. Here, we show evidence of dynamic regulation and pathological function of a nuclear miRNA in TBI.

Original languageEnglish (US)
Article number228
JournalFrontiers in Molecular Neuroscience
Volume10
DOIs
StatePublished - Jul 28 2017

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Interferon Type I
Neuroprotective Agents
Brain Injuries
MicroRNAs
Knockout Mice
Chemokine CXCL10
Inflammation
In Situ Hybridization
Traumatic Brain Injury
Hippocampus
Staining and Labeling
Neurons

Keywords

  • Gene expression
  • Inflammation
  • Injury
  • Neurodegeneration

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Induction of miR-155 after brain injury promotes type 1 interferon and has a neuroprotective effect. / Harrison, Emily B.; Emanuel, Katy; Lamberty, Benjamin G.; Morsey, Brenda M.; Li, Min; Kelso, Matthew L.; Yelamanchili, Sowmya V; Fox, Howard S.

In: Frontiers in Molecular Neuroscience, Vol. 10, 228, 28.07.2017.

Research output: Contribution to journalArticle

Harrison, Emily B. ; Emanuel, Katy ; Lamberty, Benjamin G. ; Morsey, Brenda M. ; Li, Min ; Kelso, Matthew L. ; Yelamanchili, Sowmya V ; Fox, Howard S. / Induction of miR-155 after brain injury promotes type 1 interferon and has a neuroprotective effect. In: Frontiers in Molecular Neuroscience. 2017 ; Vol. 10.
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