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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 (...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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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. |
format | Online Article Text |
id | pubmed-3744576 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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