Blockade of microglial KATP-channel abrogates suppression of inflammatory-mediated inhibition of neural precursor cells

Ortega, Francisco J., Vukovic, Jana, Rodriguez, Manuel J. and Bartlett, Perry F. (2014) Blockade of microglial KATP-channel abrogates suppression of inflammatory-mediated inhibition of neural precursor cells. GLIA, 62 2: 247-258. doi:10.1002/glia.22603

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Author Ortega, Francisco J.
Vukovic, Jana
Rodriguez, Manuel J.
Bartlett, Perry F.
Title Blockade of microglial KATP-channel abrogates suppression of inflammatory-mediated inhibition of neural precursor cells
Journal name GLIA   Check publisher's open access policy
ISSN 0894-1491
1098-1136
Publication date 2014-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.1002/glia.22603
Open Access Status File (Author Post-print)
Volume 62
Issue 2
Start page 247
End page 258
Total pages 12
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Language eng
Abstract Microglia positively affect neural progenitor cell physiology through the release of inflammatory mediators or trophic factors. We demonstrated previously that reactive microglia foster KATP-channel expression and that blocking this channel using glibenclamide administration enhances striatal neurogenesis after stroke. In this study, we investigated whether the microglial KATP-channel directly influences the activation of neural precursor cells (NPCs) from the subventricular zone using transgenic Csf1r-GFP mice. In vitro exposure of NPCs to lipopolysaccharide and interferon-gamma resulted in a significant decrease in precursor cell number. The complete removal of microglia from the culture or exposure to enriched microglia culture also decreased the precursor cell number. The addition of glibenclamide rescued the negative effects of enriched microglia on neurosphere formation and promoted a ~20% improvement in precursor cell number. Similar results were found using microglial-conditioned media from isolated microglia. Using primary mixed glial and pure microglial cultures, glibenclamide specifically targeted reactive microglia to restore neurogenesis and increased the microglial production of the chemokine monocyte chemoattractant protein-1 (MCP-1). These findings provide the first direct evidence that the microglial KATP-channel is a regulator of the proliferation of NPCs under inflammatory conditions.
Keyword Glibenclamide
Inflammation
Microglia
Neurogenesis
Neurosphere
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID IPT-2012-0614-010000
Institutional Status UQ
Additional Notes Published online: 6 December 2013.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2014 Collection
 
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Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
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