PMID- 24311472
OWN - NLM
STAT- MEDLINE
DCOM- 20140926
LR  - 20131216
IS  - 1098-1136 (Electronic)
IS  - 0894-1491 (Linking)
VI  - 62
IP  - 2
DP  - 2014 Feb
TI  - Blockade of microglial KATP -channel abrogates suppression of 
      inflammatory-mediated inhibition of neural precursor cells.
PG  - 247-58
LID - 10.1002/glia.22603 [doi]
AB  - Microglia positively affect neural progenitor cell physiology through the release 
      of inflammatory mediators or trophic factors. We demonstrated previously that 
      reactive microglia foster K(ATP) -channel expression and that blocking this 
      channel using glibenclamide administration enhances striatal neurogenesis after 
      stroke. In this study, we investigated whether the microglial K(ATP) -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  approximately 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 K(ATP) -channel is a regulator of the proliferation of NPCs under 
      inflammatory conditions.
CI  - Copyright (c) 2013 Wiley Periodicals, Inc.
FAU - Ortega, Francisco J
AU  - Ortega FJ
AD  - Biochemistry and Molecular Biology Unit, School of Medicine, University of 
      Barcelona, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS) and 
      Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas 
      (CIBERNED), Barcelona, Spain; Queensland Brain Institute, The University of 
      Queensland, Brisbane, Queensland, Australia.
FAU - Vukovic, Jana
AU  - Vukovic J
FAU - Rodriguez, Manuel J
AU  - Rodriguez MJ
FAU - Bartlett, Perry F
AU  - Bartlett PF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131206
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (Inflammation Mediators)
RN  - 0 (KATP Channels)
RN  - 0 (Lipopolysaccharides)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Inflammation/*metabolism
MH  - Inflammation Mediators/metabolism
MH  - Interferon-gamma/metabolism
MH  - KATP Channels/*antagonists & inhibitors
MH  - Lipopolysaccharides/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Microglia/drug effects/immunology/*metabolism
MH  - Neural Stem Cells/*cytology
MH  - Neurogenesis/immunology/*physiology
MH  - Neurons/drug effects/immunology/metabolism
OTO - NOTNLM
OT  - glibenclamide
OT  - inflammation
OT  - microglia
OT  - neurogenesis
OT  - neurosphere
EDAT- 2013/12/07 06:00
MHDA- 2014/09/27 06:00
CRDT- 2013/12/07 06:00
PHST- 2013/03/20 00:00 [received]
PHST- 2013/11/06 00:00 [revised]
PHST- 2013/11/08 00:00 [accepted]
PHST- 2013/12/07 06:00 [entrez]
PHST- 2013/12/07 06:00 [pubmed]
PHST- 2014/09/27 06:00 [medline]
AID - 10.1002/glia.22603 [doi]
PST - ppublish
SO  - Glia. 2014 Feb;62(2):247-58. doi: 10.1002/glia.22603. Epub 2013 Dec 6.