PMID- 29683209
OWN - NLM
STAT- MEDLINE
DCOM- 20190718
LR  - 20230606
IS  - 1098-1136 (Electronic)
IS  - 0894-1491 (Linking)
VI  - 66
IP  - 8
DP  - 2018 Aug
TI  - Inhibition of astroglial connexin43 hemichannels with TAT-Gap19 exerts 
      anticonvulsant effects in rodents.
PG  - 1788-1804
LID - 10.1002/glia.23341 [doi]
AB  - Accumulating evidence shows a key function for astrocytic connexin43 (Cx43) 
      signaling in epilepsy. However, the lack of experimental distinction between Cx43 
      gap junction channels (GJCs) and hemichannels (HCs) has impeded the 
      identification of the exact contribution of either channel configurations to 
      epilepsy. We therefore investigated whether TAT-Gap19, a Cx mimetic peptide that 
      inhibits Cx43 HCs but not the corresponding Cx43 GJCs, influences experimentally 
      induced seizures in rodents. Dye uptake experiments in acute hippocampal slices 
      of mice demonstrated that astroglial Cx43 HCs open in response to the 
      chemoconvulsant pilocarpine and this was inhibited by TAT-Gap19. In vivo, 
      pilocarpine-induced seizures as well as the accompanying increase in D-serine 
      microdialysate levels were suppressed by Cx43 HC inhibition. Moreover, the 
      anticonvulsant action of TAT-Gap19 was reversed by exogenous D-serine 
      administration, suggesting that Cx43 HC inhibition protects against seizures by 
      lowering extracellular D-serine levels. The anticonvulsive properties of Cx43 HC 
      inhibition were further confirmed in electrical seizure mouse models, i.e. an 
      acute 6 Hertz (Hz) model of refractory seizures and a chronic 6 Hz corneal 
      kindling model. Collectively, these results indicate that Cx43 HCs play a role in 
      seizures and underscore their potential as a novel and druggable target in 
      epilepsy treatment.
CI  - (c) 2018 Wiley Periodicals, Inc.
FAU - Walrave, Laura
AU  - Walrave L
AUID- ORCID: 0000-0002-7973-7595
AD  - Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, 
      Research group Experimental Pharmacology (EFAR), Center for Neurosciences (C4N), 
      Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium.
FAU - Pierre, Anouk
AU  - Pierre A
AD  - Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, 
      Research group Experimental Pharmacology (EFAR), Center for Neurosciences (C4N), 
      Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium.
FAU - Albertini, Giulia
AU  - Albertini G
AD  - Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, 
      Research group Experimental Pharmacology (EFAR), Center for Neurosciences (C4N), 
      Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium.
FAU - Aourz, Najat
AU  - Aourz N
AD  - Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, 
      Research group Experimental Pharmacology (EFAR), Center for Neurosciences (C4N), 
      Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium.
FAU - De Bundel, Dimitri
AU  - De Bundel D
AD  - Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, 
      Research group Experimental Pharmacology (EFAR), Center for Neurosciences (C4N), 
      Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium.
FAU - Van Eeckhaut, Ann
AU  - Van Eeckhaut A
AUID- ORCID: 0000-0002-1695-7398
AD  - Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, 
      Research group Experimental Pharmacology (EFAR), Center for Neurosciences (C4N), 
      Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium.
FAU - Vinken, Mathieu
AU  - Vinken M
AD  - Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit 
      Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium.
FAU - Giaume, Christian
AU  - Giaume C
AD  - Center for Interdisciplinary Research in Biology (CIRB), College de France, 
      Paris, 75005, France.
FAU - Leybaert, Luc
AU  - Leybaert L
AD  - Physiology group, Department of Basic Medical Sciences, Ghent University, De 
      Pintelaan 185, Ghent, 9000, Belgium.
FAU - Smolders, Ilse
AU  - Smolders I
AD  - Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, 
      Research group Experimental Pharmacology (EFAR), Center for Neurosciences (C4N), 
      Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium.
LA  - eng
GR  - 335476/ERC_/European Research Council/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180423
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (Anticonvulsants)
RN  - 0 (Connexin 43)
RN  - 0 (Connexins)
RN  - 0 (Peptide Fragments)
RN  - 0 (TAT-Gap19 peptide)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/pharmacology
MH  - Animals
MH  - Anticonvulsants/*pharmacology
MH  - Astrocytes/*drug effects/metabolism
MH  - Connexin 43/*metabolism
MH  - Connexins/metabolism
MH  - Gap Junctions/drug effects/metabolism
MH  - Hippocampus/drug effects/metabolism
MH  - Mice, Transgenic
MH  - Peptide Fragments/*metabolism
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - TAT-Gap19
OT  - astrocytes
OT  - connexin43 hemichannels
OT  - pilocarpine
OT  - seizures
EDAT- 2018/04/24 06:00
MHDA- 2019/07/19 06:00
CRDT- 2018/04/24 06:00
PHST- 2017/08/30 00:00 [received]
PHST- 2018/04/04 00:00 [revised]
PHST- 2018/04/04 00:00 [accepted]
PHST- 2018/04/24 06:00 [pubmed]
PHST- 2019/07/19 06:00 [medline]
PHST- 2018/04/24 06:00 [entrez]
AID - 10.1002/glia.23341 [doi]
PST - ppublish
SO  - Glia. 2018 Aug;66(8):1788-1804. doi: 10.1002/glia.23341. Epub 2018 Apr 23.