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Heavy Alcohol Exposure Activates Astroglial Hemichannels and Pannexons in the Hippocampus of Adolescent Rats: Effects on Neuroinflammation and Astrocyte Arborization

A mounting body of evidence indicates that adolescents are specially more susceptible to alcohol influence than adults. However, the mechanisms underlying this phenomenon remain poorly understood. Astrocyte-mediated gliotransmission is crucial for hippocampal plasticity and recently, the opening of...

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Autores principales: Gómez, Gonzalo I., Falcon, Romina V., Maturana, Carola J., Labra, Valeria C., Salgado, Nicole, Rojas, Consuelo A., Oyarzun, Juan E., Cerpa, Waldo, Quintanilla, Rodrigo A., Orellana, Juan A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288256/
https://www.ncbi.nlm.nih.gov/pubmed/30564103
http://dx.doi.org/10.3389/fncel.2018.00472
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author Gómez, Gonzalo I.
Falcon, Romina V.
Maturana, Carola J.
Labra, Valeria C.
Salgado, Nicole
Rojas, Consuelo A.
Oyarzun, Juan E.
Cerpa, Waldo
Quintanilla, Rodrigo A.
Orellana, Juan A.
author_facet Gómez, Gonzalo I.
Falcon, Romina V.
Maturana, Carola J.
Labra, Valeria C.
Salgado, Nicole
Rojas, Consuelo A.
Oyarzun, Juan E.
Cerpa, Waldo
Quintanilla, Rodrigo A.
Orellana, Juan A.
author_sort Gómez, Gonzalo I.
collection PubMed
description A mounting body of evidence indicates that adolescents are specially more susceptible to alcohol influence than adults. However, the mechanisms underlying this phenomenon remain poorly understood. Astrocyte-mediated gliotransmission is crucial for hippocampal plasticity and recently, the opening of hemichannels and pannexons has been found to participate in both processes. Here, we evaluated whether adolescent rats exposed to ethanol exhibit changes in the activity of astrocyte hemichannels and pannexons in the hippocampus, as well as alterations in astrocyte arborization and cytokine levels. Adolescent rats were subjected to ethanol (3.0 g/kg) for two successive days at 48-h periods over 14 days. The opening of hemichannels and pannexons was examined in hippocampal slices by dye uptake, whereas hippocampal cytokine levels and astroglial arborization were determined by ELISA and Sholl analysis, respectively. We found that adolescent ethanol exposure increased the opening of connexin 43 (Cx43) hemichannels and pannexin-1 (Panx1) channels in astrocytes. Blockade of p38 mitogen-activated protein kinase (MAPK), inducible nitric oxide synthase (iNOS) and cyclooxygenases (COXs), as well as chelation of intracellular Ca(2+), drastically reduced the ethanol-induced channel opening in astrocytes. Importantly, ethanol-induced Cx43 hemichannel and Panx1 channel activity was correlated with increased levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6 in the hippocampus, as well as with profound alterations in astrocyte arbor complexity. Thus, we propose that uncontrolled opening of astrocyte hemichannels and pannexons may contribute not only to the glial dysfunction and neurotoxicity caused by adolescent alcohol consumption, but also to the pathogenesis of alcohol use disorders in the adulthood.
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spelling pubmed-62882562018-12-18 Heavy Alcohol Exposure Activates Astroglial Hemichannels and Pannexons in the Hippocampus of Adolescent Rats: Effects on Neuroinflammation and Astrocyte Arborization Gómez, Gonzalo I. Falcon, Romina V. Maturana, Carola J. Labra, Valeria C. Salgado, Nicole Rojas, Consuelo A. Oyarzun, Juan E. Cerpa, Waldo Quintanilla, Rodrigo A. Orellana, Juan A. Front Cell Neurosci Neuroscience A mounting body of evidence indicates that adolescents are specially more susceptible to alcohol influence than adults. However, the mechanisms underlying this phenomenon remain poorly understood. Astrocyte-mediated gliotransmission is crucial for hippocampal plasticity and recently, the opening of hemichannels and pannexons has been found to participate in both processes. Here, we evaluated whether adolescent rats exposed to ethanol exhibit changes in the activity of astrocyte hemichannels and pannexons in the hippocampus, as well as alterations in astrocyte arborization and cytokine levels. Adolescent rats were subjected to ethanol (3.0 g/kg) for two successive days at 48-h periods over 14 days. The opening of hemichannels and pannexons was examined in hippocampal slices by dye uptake, whereas hippocampal cytokine levels and astroglial arborization were determined by ELISA and Sholl analysis, respectively. We found that adolescent ethanol exposure increased the opening of connexin 43 (Cx43) hemichannels and pannexin-1 (Panx1) channels in astrocytes. Blockade of p38 mitogen-activated protein kinase (MAPK), inducible nitric oxide synthase (iNOS) and cyclooxygenases (COXs), as well as chelation of intracellular Ca(2+), drastically reduced the ethanol-induced channel opening in astrocytes. Importantly, ethanol-induced Cx43 hemichannel and Panx1 channel activity was correlated with increased levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6 in the hippocampus, as well as with profound alterations in astrocyte arbor complexity. Thus, we propose that uncontrolled opening of astrocyte hemichannels and pannexons may contribute not only to the glial dysfunction and neurotoxicity caused by adolescent alcohol consumption, but also to the pathogenesis of alcohol use disorders in the adulthood. Frontiers Media S.A. 2018-12-04 /pmc/articles/PMC6288256/ /pubmed/30564103 http://dx.doi.org/10.3389/fncel.2018.00472 Text en Copyright © 2018 Gómez, Falcon, Maturana, Labra, Salgado, Rojas, Oyarzun, Cerpa, Quintanilla and Orellana. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Gómez, Gonzalo I.
Falcon, Romina V.
Maturana, Carola J.
Labra, Valeria C.
Salgado, Nicole
Rojas, Consuelo A.
Oyarzun, Juan E.
Cerpa, Waldo
Quintanilla, Rodrigo A.
Orellana, Juan A.
Heavy Alcohol Exposure Activates Astroglial Hemichannels and Pannexons in the Hippocampus of Adolescent Rats: Effects on Neuroinflammation and Astrocyte Arborization
title Heavy Alcohol Exposure Activates Astroglial Hemichannels and Pannexons in the Hippocampus of Adolescent Rats: Effects on Neuroinflammation and Astrocyte Arborization
title_full Heavy Alcohol Exposure Activates Astroglial Hemichannels and Pannexons in the Hippocampus of Adolescent Rats: Effects on Neuroinflammation and Astrocyte Arborization
title_fullStr Heavy Alcohol Exposure Activates Astroglial Hemichannels and Pannexons in the Hippocampus of Adolescent Rats: Effects on Neuroinflammation and Astrocyte Arborization
title_full_unstemmed Heavy Alcohol Exposure Activates Astroglial Hemichannels and Pannexons in the Hippocampus of Adolescent Rats: Effects on Neuroinflammation and Astrocyte Arborization
title_short Heavy Alcohol Exposure Activates Astroglial Hemichannels and Pannexons in the Hippocampus of Adolescent Rats: Effects on Neuroinflammation and Astrocyte Arborization
title_sort heavy alcohol exposure activates astroglial hemichannels and pannexons in the hippocampus of adolescent rats: effects on neuroinflammation and astrocyte arborization
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288256/
https://www.ncbi.nlm.nih.gov/pubmed/30564103
http://dx.doi.org/10.3389/fncel.2018.00472
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