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The β2-adrenoceptor agonist clenbuterol elicits neuroprotective, anti-inflammatory and neurotrophic actions in the kainic acid model of excitotoxicity.
Brain Behav Immun. 2010 Nov; 24(8):1354-61.BB

Abstract

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.

Authors+Show Affiliations

Neuropsychopharmacology Research Group, School of Pharmacy and Pharmaceutical Sciences, Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20599496

Citation

Gleeson, Lorna C., et al. "The Β2-adrenoceptor Agonist Clenbuterol Elicits Neuroprotective, Anti-inflammatory and Neurotrophic Actions in the Kainic Acid Model of Excitotoxicity." Brain, Behavior, and Immunity, vol. 24, no. 8, 2010, pp. 1354-61.
Gleeson LC, Ryan KJ, Griffin EW, et al. The β2-adrenoceptor agonist clenbuterol elicits neuroprotective, anti-inflammatory and neurotrophic actions in the kainic acid model of excitotoxicity. Brain Behav Immun. 2010;24(8):1354-61.
Gleeson, L. C., Ryan, K. J., Griffin, E. W., Connor, T. J., & Harkin, A. (2010). The β2-adrenoceptor agonist clenbuterol elicits neuroprotective, anti-inflammatory and neurotrophic actions in the kainic acid model of excitotoxicity. Brain, Behavior, and Immunity, 24(8), 1354-61. https://doi.org/10.1016/j.bbi.2010.06.015
Gleeson LC, et al. The Β2-adrenoceptor Agonist Clenbuterol Elicits Neuroprotective, Anti-inflammatory and Neurotrophic Actions in the Kainic Acid Model of Excitotoxicity. Brain Behav Immun. 2010;24(8):1354-61. PubMed PMID: 20599496.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The β2-adrenoceptor agonist clenbuterol elicits neuroprotective, anti-inflammatory and neurotrophic actions in the kainic acid model of excitotoxicity. AU - Gleeson,Lorna C, AU - Ryan,Katie J, AU - Griffin,Eadaoin W, AU - Connor,Thomas J, AU - Harkin,Andrew, Y1 - 2010/07/03/ PY - 2010/03/09/received PY - 2010/06/14/revised PY - 2010/06/27/accepted PY - 2010/7/6/entrez PY - 2010/7/6/pubmed PY - 2011/1/22/medline SP - 1354 EP - 61 JF - Brain, behavior, and immunity JO - Brain Behav Immun VL - 24 IS - 8 N2 - 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. SN - 1090-2139 UR - https://www.unboundmedicine.com/medline/citation/20599496/The_β2_adrenoceptor_agonist_clenbuterol_elicits_neuroprotective_anti_inflammatory_and_neurotrophic_actions_in_the_kainic_acid_model_of_excitotoxicity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0889-1591(10)00174-1 DB - PRIME DP - Unbound Medicine ER -