| Attenuation of microglial and IL-1 signaling protects mice from acute alcohol-induced sedation and/or motor impairment. | |
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MedLine Citation:
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PMID: 21276848 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Alcohol-induced proinflammatory central immune signaling has been implicated in the chronic neurotoxic actions of alcohol, although little work has examined if these non-neuronal actions contribute to the acute behavioral responses elicited by alcohol administration. The present study examined if acute alcohol-induced sedation (loss of righting reflex, sleep time test) and motor impairment (rotarod test) were influenced by acute alcohol-induced microglial-dependent central immune signaling. Inhibition of acute alcohol-induced central immune signaling, through the reduction of proinflammatory microglial activation with minocycline, or by blocking interleukin-1 (IL-1) receptor signaling using IL-1 receptor antagonist (IL-1ra), reduced acute alcohol-induced sedation in mice. Mice treated with IL-1ra recovered faster from acute alcohol-induced motor impairment than control animals. However, minocycline led to greater motor impairment induced by alcohol, implicating different mechanisms in alcohol-induced sedation and motor impairment. At a cellular level, IκBα protein levels in mixed hippocampal cells responded rapidly to alcohol in a time-dependent manner, and both minocycline and IL-1ra attenuated the elevated levels of IκBα protein by alcohol. Collectively these data suggest that alcohol is capable of rapid modification of proinflammatory immune signaling in the brain and this contributes significantly to the pharmacology of alcohol. |
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Authors:
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Yue Wu; Erin L Lousberg; Lachlan M Moldenhauer; John D Hayball; Sarah A Robertson; Janet K Coller; Linda R Watkins; Andrew A Somogyi; Mark R Hutchinson |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-1-26 |
Journal Detail:
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Title: Brain, behavior, and immunity Volume: - ISSN: 1090-2139 ISO Abbreviation: - Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-1-31 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8800478 Medline TA: Brain Behav Immun Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier Inc. |
Affiliation:
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Discipline of Pharmacology, School of Medical Sciences, University of Adelaide, South Australia, Australia. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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