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Heavy alcohol exposure activates astroglial hemichannels and pannexons in the hippocampus of adolescent rats: Effects on neuroinflammation and astrocyte arborization
dc.contributor.author | Gómez G.I. | |
dc.contributor.author | Falcon R.V. | |
dc.contributor.author | Maturana C.J. | |
dc.contributor.author | Labra V.C. | |
dc.contributor.author | Salgado N. | |
dc.contributor.author | Rojas C.A. | |
dc.contributor.author | Oyarzun J.E. | |
dc.contributor.author | Cerpa W. | |
dc.contributor.author | Quintanilla R.A. | |
dc.contributor.author | Orellana J.A. | |
dc.date.accessioned | 2020-09-02T22:19:53Z | |
dc.date.available | 2020-09-02T22:19:53Z | |
dc.date.issued | 2018 | |
dc.identifier | 10.3389/fncel.2018.00472 | |
dc.identifier.citation | 12, , - | |
dc.identifier.issn | 16625102 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12728/4792 | |
dc.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. © 2018 Gómez, Falcon, Maturana, Labra, Salgado, Rojas, Oyarzun, Cerpa, Quintanilla and Orellana. | |
dc.language.iso | en | |
dc.publisher | Frontiers Media S.A. | |
dc.subject | Alcoholism | |
dc.subject | Astrocyte | |
dc.subject | Connexins | |
dc.subject | Cytokines | |
dc.subject | Glia | |
dc.subject | Hippocampus | |
dc.subject | Pannexins | |
dc.subject | 4 (4 fluorophenyl) 2 (4 hydroxyphenyl) 5 (4 pyridyl)imidazole | |
dc.subject | connexin 43 | |
dc.subject | cyclooxygenase 1 | |
dc.subject | cyclooxygenase 2 | |
dc.subject | cytokine | |
dc.subject | gamma interferon | |
dc.subject | gap junction protein | |
dc.subject | glial fibrillary acidic protein | |
dc.subject | inducible nitric oxide synthase | |
dc.subject | interleukin 1beta | |
dc.subject | interleukin 6 | |
dc.subject | mitogen activated protein kinase p38 | |
dc.subject | pannexin 1 | |
dc.subject | pannexon | |
dc.subject | prostaglandin E2 | |
dc.subject | prostaglandin synthase | |
dc.subject | tumor necrosis factor | |
dc.subject | unclassified drug | |
dc.subject | adolescent | |
dc.subject | alcohol consumption | |
dc.subject | alcoholism | |
dc.subject | animal cell | |
dc.subject | animal experiment | |
dc.subject | animal model | |
dc.subject | animal tissue | |
dc.subject | antibody detection | |
dc.subject | Article | |
dc.subject | astrocyte | |
dc.subject | brain dysfunction | |
dc.subject | calcium cell level | |
dc.subject | cell structure | |
dc.subject | cell survival | |
dc.subject | confocal microscopy | |
dc.subject | controlled study | |
dc.subject | enzyme linked immunosorbent assay | |
dc.subject | glia cell | |
dc.subject | hippocampus | |
dc.subject | image analysis | |
dc.subject | image processing | |
dc.subject | male | |
dc.subject | membrane channel | |
dc.subject | nerve cell plasticity | |
dc.subject | nerve fiber | |
dc.subject | nervous system inflammation | |
dc.subject | nonhuman | |
dc.subject | pathogenesis | |
dc.subject | rat | |
dc.subject | signal transduction | |
dc.subject | synaptic transmission | |
dc.subject | toxicity and intoxication | |
dc.title | Heavy alcohol exposure activates astroglial hemichannels and pannexons in the hippocampus of adolescent rats: Effects on neuroinflammation and astrocyte arborization | |
dc.type | Article |