| The β2-adrenoceptor agonist clenbuterol elicits neuroprotective, anti-inflammatory and neurotrophic actions in the kainic acid model of excitotoxicity. | |
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MedLine Citation:
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PMID: 20599496 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Excitotoxicity is a mechanism of neuronal cell death implicated in a range of neurodegenerative conditions. Systemic administration of the excitotoxin kainic acid (KA) induces inflammation and apoptosis in the hippocampus, resulting in neuronal loss. Evidence indicates that stimulation of glial β(2)-adrenoceptors has anti-inflammatory and neurotrophic properties that could result in neuroprotection. Consequently, in this study we examined the effect of the β(2)-adrenoceptor agonist clenbuterol on KA-induced inflammation, neurotrophic factor expression and apoptosis in the hippocampus. Clenbuterol (0.5mg/kg) was administered to rats one hour prior to KA (10mg/kg). Epileptic behaviour induced by KA was assessed for three hours following administration using the Racine scale. Twenty-four hours later TUNEL staining in the CA3 hippocampal subfield and hippocampal caspase-3 activity was assessed to measure KA-induced apoptosis. In addition, expression of inflammatory cytokines (IL-1β and IFN-γ), inducible nitric oxide synthase (iNOS), kynurenine pathway enzymes indolamine 2,3-dioxygenase (IDO) and kynurenine monooxygenase (KMO), the microglial activation marker CD11b, and the neurotrophins BDNF and NGF were quantified in the hippocampus using real-time PCR. Whilst clenbuterol treatment did not significantly alter KA-induced epileptic behavior it ameliorated KA-induced apoptosis, and this neuroprotective effect was accompanied by reduced inflammatory cytokine expression, reduced expression of iNOS, IDO, KMO and CD11b, coupled with increased BDNF and NGF expression in KA-treated rats. In conclusion, the β(2)-adrenoceptor agonist clenbuterol has anti-inflammatory and neurotrophic actions and elicits a neuroprotective effect in the KA model of neurodegeneration. |
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Authors:
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Lorna C Gleeson; Katie J Ryan; Eadaoin W Griffin; Thomas J Connor; Andrew Harkin |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-03 |
Journal Detail:
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Title: Brain, behavior, and immunity Volume: 24 ISSN: 1090-2139 ISO Abbreviation: Brain Behav. Immun. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-04 Completed Date: 2011-01-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8800478 Medline TA: Brain Behav Immun Country: United States |
Other Details:
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Languages: eng Pagination: 1354-61 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Neuropsychopharmacology Research Group, School of Pharmacy and Pharmaceutical Sciences, Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic beta-3 Receptor Agonists
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pharmacology* Animals Anti-Inflammatory Agents* Apoptosis / drug effects Brain-Derived Neurotrophic Factor / metabolism Caspase 3 / metabolism Clenbuterol / pharmacology* Excitatory Amino Acid Agonists / toxicity* Hippocampus / pathology In Situ Nick-End Labeling Kainic Acid / antagonists & inhibitors*, toxicity* Male Nerve Growth Factors / metabolism* Neuroprotective Agents* Neurotoxicity Syndromes / pathology, prevention & control* Neurotoxins / toxicity* Rats Rats, Wistar Reverse Transcriptase Polymerase Chain Reaction Seizures / chemically induced, prevention & control |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic beta-3 Receptor Agonists; 0/Anti-Inflammatory Agents; 0/Brain-Derived Neurotrophic Factor; 0/Excitatory Amino Acid Agonists; 0/Nerve Growth Factors; 0/Neuroprotective Agents; 0/Neurotoxins; 37148-27-9/Clenbuterol; 487-79-6/Kainic Acid; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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