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Age-Dependent Relevance of Endogenous 5-Lipoxygenase Derivatives in Anxiety-Like Behavior in Mice

When 5-lipoxygenase (5-LO) is inhibited, roughly half of the CNS effect of the prototypic endocannabinoid anandamide (AEA) is lost. Therefore, we decided to investigate whether inhibiting this enzyme would influence physiological functions classically described as being under control of the endocann...

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Autores principales: Leo, Luciana M., Almeida-Corrêa, Suellen, Canetti, Claudio A., Amaral, Olavo B., Bozza, Fernando A., Pamplona, Fabricio A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3885659/
https://www.ncbi.nlm.nih.gov/pubmed/24416334
http://dx.doi.org/10.1371/journal.pone.0085009
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author Leo, Luciana M.
Almeida-Corrêa, Suellen
Canetti, Claudio A.
Amaral, Olavo B.
Bozza, Fernando A.
Pamplona, Fabricio A.
author_facet Leo, Luciana M.
Almeida-Corrêa, Suellen
Canetti, Claudio A.
Amaral, Olavo B.
Bozza, Fernando A.
Pamplona, Fabricio A.
author_sort Leo, Luciana M.
collection PubMed
description When 5-lipoxygenase (5-LO) is inhibited, roughly half of the CNS effect of the prototypic endocannabinoid anandamide (AEA) is lost. Therefore, we decided to investigate whether inhibiting this enzyme would influence physiological functions classically described as being under control of the endocannabinoid system. Although 5-LO inhibition by MK-886 reduced lipoxin A(4) levels in the brain, no effect was found in the elevated plus maze (EPM), even at the highest possible doses, via i.p. (10 mg/kg,) or i.c.v. (500 pmol/2 µl) routes. Accordingly, no alterations in anxiety-like behavior in the EPM test were observed in 5-LO KO mice. Interestingly, aged mice, which show reduced circulating lipoxin A(4) levels, were sensitive to MK-886, displaying an anxiogenic-like state in response to treatment. Moreover, exogenous lipoxin A(4) induced an anxiolytic-like profile in the EPM test. Our findings are in line with other reports showing no difference between FLAP KO or 5-LO KO and their control strains in adult mice, but increased anxiety-like behavior in aged mice. We also show for the first time that lipoxin A(4) affects mouse behavior. In conclusion, we propose an age-dependent relevancy of endogenous 5-LO derivatives in the modulation of anxiety-like behavior, in addition to a potential for exogenous lipoxin A(4) in producing an anxiolytic-like state.
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spelling pubmed-38856592014-01-10 Age-Dependent Relevance of Endogenous 5-Lipoxygenase Derivatives in Anxiety-Like Behavior in Mice Leo, Luciana M. Almeida-Corrêa, Suellen Canetti, Claudio A. Amaral, Olavo B. Bozza, Fernando A. Pamplona, Fabricio A. PLoS One Research Article When 5-lipoxygenase (5-LO) is inhibited, roughly half of the CNS effect of the prototypic endocannabinoid anandamide (AEA) is lost. Therefore, we decided to investigate whether inhibiting this enzyme would influence physiological functions classically described as being under control of the endocannabinoid system. Although 5-LO inhibition by MK-886 reduced lipoxin A(4) levels in the brain, no effect was found in the elevated plus maze (EPM), even at the highest possible doses, via i.p. (10 mg/kg,) or i.c.v. (500 pmol/2 µl) routes. Accordingly, no alterations in anxiety-like behavior in the EPM test were observed in 5-LO KO mice. Interestingly, aged mice, which show reduced circulating lipoxin A(4) levels, were sensitive to MK-886, displaying an anxiogenic-like state in response to treatment. Moreover, exogenous lipoxin A(4) induced an anxiolytic-like profile in the EPM test. Our findings are in line with other reports showing no difference between FLAP KO or 5-LO KO and their control strains in adult mice, but increased anxiety-like behavior in aged mice. We also show for the first time that lipoxin A(4) affects mouse behavior. In conclusion, we propose an age-dependent relevancy of endogenous 5-LO derivatives in the modulation of anxiety-like behavior, in addition to a potential for exogenous lipoxin A(4) in producing an anxiolytic-like state. Public Library of Science 2014-01-08 /pmc/articles/PMC3885659/ /pubmed/24416334 http://dx.doi.org/10.1371/journal.pone.0085009 Text en © 2014 Leo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Leo, Luciana M.
Almeida-Corrêa, Suellen
Canetti, Claudio A.
Amaral, Olavo B.
Bozza, Fernando A.
Pamplona, Fabricio A.
Age-Dependent Relevance of Endogenous 5-Lipoxygenase Derivatives in Anxiety-Like Behavior in Mice
title Age-Dependent Relevance of Endogenous 5-Lipoxygenase Derivatives in Anxiety-Like Behavior in Mice
title_full Age-Dependent Relevance of Endogenous 5-Lipoxygenase Derivatives in Anxiety-Like Behavior in Mice
title_fullStr Age-Dependent Relevance of Endogenous 5-Lipoxygenase Derivatives in Anxiety-Like Behavior in Mice
title_full_unstemmed Age-Dependent Relevance of Endogenous 5-Lipoxygenase Derivatives in Anxiety-Like Behavior in Mice
title_short Age-Dependent Relevance of Endogenous 5-Lipoxygenase Derivatives in Anxiety-Like Behavior in Mice
title_sort age-dependent relevance of endogenous 5-lipoxygenase derivatives in anxiety-like behavior in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3885659/
https://www.ncbi.nlm.nih.gov/pubmed/24416334
http://dx.doi.org/10.1371/journal.pone.0085009
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