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Disruption in Connexin-Based Communication Is Associated with Intracellular Ca(2+) Signal Alterations in Astrocytes from Niemann-Pick Type C Mice

Reduced astrocytic gap junctional communication and enhanced hemichannel activity were recently shown to increase astroglial and neuronal vulnerability to neuroinflammation. Moreover, increasing evidence suggests that neuroinflammation plays a pivotal role in the development of Niemann-Pick type C (...

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Autores principales: Sáez, Pablo J., Orellana, Juan A., Vega-Riveros, Natalia, Figueroa, Vania A., Hernández, Diego E., Castro, Juan F., Klein, Andrés D., Jiang, Jean X., Zanlungo, Silvana, Sáez, Juan C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744576/
https://www.ncbi.nlm.nih.gov/pubmed/23977027
http://dx.doi.org/10.1371/journal.pone.0071361
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author Sáez, Pablo J.
Orellana, Juan A.
Vega-Riveros, Natalia
Figueroa, Vania A.
Hernández, Diego E.
Castro, Juan F.
Klein, Andrés D.
Jiang, Jean X.
Zanlungo, Silvana
Sáez, Juan C.
author_facet Sáez, Pablo J.
Orellana, Juan A.
Vega-Riveros, Natalia
Figueroa, Vania A.
Hernández, Diego E.
Castro, Juan F.
Klein, Andrés D.
Jiang, Jean X.
Zanlungo, Silvana
Sáez, Juan C.
author_sort Sáez, Pablo J.
collection PubMed
description Reduced astrocytic gap junctional communication and enhanced hemichannel activity were recently shown to increase astroglial and neuronal vulnerability to neuroinflammation. Moreover, increasing evidence suggests that neuroinflammation plays a pivotal role in the development of Niemann-Pick type C (NPC) disease, an autosomal lethal neurodegenerative disorder that is mainly caused by mutations in the NPC1 gene. Therefore, we investigated whether the lack of NPC1 expression in murine astrocytes affects the functional state of gap junction channels and hemichannels. Cultured cortical astrocytes of NPC1 knock-out mice (Npc1(−/−)) showed reduced intercellular communication via gap junctions and increased hemichannel activity. Similarly, astrocytes of newborn Npc1(−/−) hippocampal slices presented high hemichannel activity, which was completely abrogated by connexin 43 hemichannel blockers and was resistant to inhibitors of pannexin 1 hemichannels. Npc1(−/−) astrocytes also showed more intracellular Ca(2+) signal oscillations mediated by functional connexin 43 hemichannels and P2Y(1) receptors. Therefore, Npc1(−/−) astrocytes present features of connexin based channels compatible with those of reactive astrocytes and hemichannels might be a novel therapeutic target to reduce neuroinflammation in NPC disease.
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spelling pubmed-37445762013-08-23 Disruption in Connexin-Based Communication Is Associated with Intracellular Ca(2+) Signal Alterations in Astrocytes from Niemann-Pick Type C Mice Sáez, Pablo J. Orellana, Juan A. Vega-Riveros, Natalia Figueroa, Vania A. Hernández, Diego E. Castro, Juan F. Klein, Andrés D. Jiang, Jean X. Zanlungo, Silvana Sáez, Juan C. PLoS One Research Article Reduced astrocytic gap junctional communication and enhanced hemichannel activity were recently shown to increase astroglial and neuronal vulnerability to neuroinflammation. Moreover, increasing evidence suggests that neuroinflammation plays a pivotal role in the development of Niemann-Pick type C (NPC) disease, an autosomal lethal neurodegenerative disorder that is mainly caused by mutations in the NPC1 gene. Therefore, we investigated whether the lack of NPC1 expression in murine astrocytes affects the functional state of gap junction channels and hemichannels. Cultured cortical astrocytes of NPC1 knock-out mice (Npc1(−/−)) showed reduced intercellular communication via gap junctions and increased hemichannel activity. Similarly, astrocytes of newborn Npc1(−/−) hippocampal slices presented high hemichannel activity, which was completely abrogated by connexin 43 hemichannel blockers and was resistant to inhibitors of pannexin 1 hemichannels. Npc1(−/−) astrocytes also showed more intracellular Ca(2+) signal oscillations mediated by functional connexin 43 hemichannels and P2Y(1) receptors. Therefore, Npc1(−/−) astrocytes present features of connexin based channels compatible with those of reactive astrocytes and hemichannels might be a novel therapeutic target to reduce neuroinflammation in NPC disease. Public Library of Science 2013-08-15 /pmc/articles/PMC3744576/ /pubmed/23977027 http://dx.doi.org/10.1371/journal.pone.0071361 Text en © 2013 Sáez et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Sáez, Pablo J.
Orellana, Juan A.
Vega-Riveros, Natalia
Figueroa, Vania A.
Hernández, Diego E.
Castro, Juan F.
Klein, Andrés D.
Jiang, Jean X.
Zanlungo, Silvana
Sáez, Juan C.
Disruption in Connexin-Based Communication Is Associated with Intracellular Ca(2+) Signal Alterations in Astrocytes from Niemann-Pick Type C Mice
title Disruption in Connexin-Based Communication Is Associated with Intracellular Ca(2+) Signal Alterations in Astrocytes from Niemann-Pick Type C Mice
title_full Disruption in Connexin-Based Communication Is Associated with Intracellular Ca(2+) Signal Alterations in Astrocytes from Niemann-Pick Type C Mice
title_fullStr Disruption in Connexin-Based Communication Is Associated with Intracellular Ca(2+) Signal Alterations in Astrocytes from Niemann-Pick Type C Mice
title_full_unstemmed Disruption in Connexin-Based Communication Is Associated with Intracellular Ca(2+) Signal Alterations in Astrocytes from Niemann-Pick Type C Mice
title_short Disruption in Connexin-Based Communication Is Associated with Intracellular Ca(2+) Signal Alterations in Astrocytes from Niemann-Pick Type C Mice
title_sort disruption in connexin-based communication is associated with intracellular ca(2+) signal alterations in astrocytes from niemann-pick type c mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744576/
https://www.ncbi.nlm.nih.gov/pubmed/23977027
http://dx.doi.org/10.1371/journal.pone.0071361
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