Activated microglia impairs neuroglial interaction by opening Cx43 hemichannels in hippocampal astrocytes.
Glia. 2015-01-30; 63(5): 795-811
DOI: 10.1002/glia.22785
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1. Glia. 2015 May;63(5):795-811. doi: 10.1002/glia.22785. Epub 2015 Jan 30.
Activated microglia impairs neuroglial interaction by opening Cx43 hemichannels
in hippocampal astrocytes.
Abudara V(1), Roux L, Dallérac G, Matias I, Dulong J, Mothet JP, Rouach N, Giaume
C.
Author information:
(1)Collège de France, Center for Interdisciplinary Research in Biology
(CIRB)/Centre National de la Recherche Scientifique, Unité Mixte de Recherche
7241/Institut National de la Santé et de la Recherche Médicale U1050, Paris
Cedex, France; University Pierre et Marie Curie, ED, Paris, France; MEMOLIFE
Laboratory of Excellence and Paris Science Lettre Research University, Paris,
France; Departamento de Fisiología, Facultad de Medicina, Universidad de la
República, Montevideo, Uruguay.
Glia plays an active role in neuronal functions and dysfunctions, some of which
depend on the expression of astrocyte connexins, the gap junction channel and
hemichannel proteins. Under neuroinflammation triggered by the endotoxin
lipopolysacharide (LPS), microglia is primary stimulated and releases
proinflammatory agents affecting astrocytes and neurons. Here, we investigate the
effects of such microglial activation on astrocyte connexin-based channel
functions and their consequences on synaptic activity in an ex vivo model. We
found that LPS induces astroglial hemichannel opening in acute hippocampal slices
while no change is observed in gap junctional communication. Based on
pharmacological and genetic approaches we found that the LPS-induced hemichannel
opening is mainly due to Cx43 hemichannel activity. This process primarily
requires a microglial stimulation resulting in the release of at least two
proinflammatory cytokines, IL-1β and TNF-α. Consequences of the
hemichannel-mediated increase in membrane permeability are a calcium rise in
astrocytes and an enhanced glutamate release associated to a reduction in
excitatory synaptic activity of pyramidal neurons in response to Schaffer’s
collateral stimulation. As a whole our findings point out astroglial hemichannels
as key determinants of the impairment of synaptic transmission during
neuroinflammation.
© 2015 Wiley Periodicals, Inc.
DOI: 10.1002/glia.22785
PMID: 25643695 [Indexed for MEDLINE]