CB2 cannabinoid receptors modulate HIF-1α and TIM-3 expression in a hypoxia-ischemia mouse model

The role of CB2 cannabinoid receptors (CB2R) in global brain lesions induced by hypoxia-ischemia (HI) insult is still unresolved. The aim of this study was to evaluate the involvement of CB2R in the behavioural and biochemical underpinnings related to brain damage induced by HI in adult mice, and th...

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Detalles Bibliográficos
Autores: Kossatz, Elk, Maldonado, Rafael, 1961-, Robledo, Patricia, 1958-
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2016
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/30847
Acceso en línea:http://hdl.handle.net/10230/30847
http://dx.doi.org/10.1016/j.euroneuro.2016.10.003
Access Level:acceso abierto
Palabra clave:Cervell -- Ferides i lesions
Isquèmia
Anoxèmia
Cannabinoides -- Receptors
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spelling CB2 cannabinoid receptors modulate HIF-1α and TIM-3 expression in a hypoxia-ischemia mouse modelKossatz, ElkMaldonado, Rafael, 1961-Robledo, Patricia, 1958-Cervell -- Ferides i lesionsIsquèmiaAnoxèmiaCannabinoides -- ReceptorsThe role of CB2 cannabinoid receptors (CB2R) in global brain lesions induced by hypoxia-ischemia (HI) insult is still unresolved. The aim of this study was to evaluate the involvement of CB2R in the behavioural and biochemical underpinnings related to brain damage induced by HI in adult mice, and the mechanisms involved. CB2R knockout (KO) mice and wild-type littermates (WT) underwent permanent ligation of the left common carotid artery and hypoxia. Behavioural measurements in the rotarod, beam walking, object recognition, open field, and Irwin tests were carried out 24h, 72h and 7 days. In KO mice, more extensive brain injury was observed. Behavioural deficits in the Irwin test were observed in both genotypes; while WT mice showed progressive recovery by day 7, KO mice did not. Only KO mice showed alterations in motor learning, coordination and balance, and did not recover over time. A higher expression of microglia and astrocytes was observed in several brain areas of lesioned WT and KO mice. The possible alteration of the inflammatory-related factors HIF-1α and TIM-3 was evaluated in these animals. In both genotypes, HIF-1α and TIM-3 expression was observed in lesioned areas associated with activated microglia. However, the expression levels of these proteins were exacerbated in KO mice in several lesioned and non-lesioned brain structures. Our results indicate that CB2R may have a crucial neuroprotective role following HI insult through the modulation of the inflammatory-related HIF-1α/TIM-3 signalling pathway in microglia.This work was supported by the European Commission, FP7 (#HEALTH-F2-2013-602891), the Spanish Ministerio de Economía y Competitividad-MINECO (#SAF2014-59648-P), the Spanish Instituto de Salud Carlos III, RETICS-RTA (#RD12/0028/0023) and the Generalitat de Catalunya, AGAUR (#2014-SGR-1547). C.L.P. and R.N. are recipients of a predoctoral fellowship from the Spanish Ministerio de Educación, Cultura y Deporte (MECD) and the Spanish MINECO, respectively. I.M.L.M. is a recipient of a predoctoral fellowship from the Mexican Consejo Nacional de Ciencia y Tecnología (CONACyT). FEDER partial funding is also acknowledgedElsevier20172016info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/30847http://dx.doi.org/10.1016/j.euroneuro.2016.10.003reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésEuropean Neuropsychopharmacology. 2016 Dec;26(12):1972-88info:eu-repo/grantAgreement/EC/FP7/602891info:eu-repo/grantAgreement/ES/1PE/SAF2014-59648-P© Elsevier http://dx.doi.org/10.1016/j.euroneuro.2016.10.003info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/308472026-06-12T07:21:37Z
dc.title.none.fl_str_mv CB2 cannabinoid receptors modulate HIF-1α and TIM-3 expression in a hypoxia-ischemia mouse model
title CB2 cannabinoid receptors modulate HIF-1α and TIM-3 expression in a hypoxia-ischemia mouse model
spellingShingle CB2 cannabinoid receptors modulate HIF-1α and TIM-3 expression in a hypoxia-ischemia mouse model
Kossatz, Elk
Cervell -- Ferides i lesions
Isquèmia
Anoxèmia
Cannabinoides -- Receptors
title_short CB2 cannabinoid receptors modulate HIF-1α and TIM-3 expression in a hypoxia-ischemia mouse model
title_full CB2 cannabinoid receptors modulate HIF-1α and TIM-3 expression in a hypoxia-ischemia mouse model
title_fullStr CB2 cannabinoid receptors modulate HIF-1α and TIM-3 expression in a hypoxia-ischemia mouse model
title_full_unstemmed CB2 cannabinoid receptors modulate HIF-1α and TIM-3 expression in a hypoxia-ischemia mouse model
title_sort CB2 cannabinoid receptors modulate HIF-1α and TIM-3 expression in a hypoxia-ischemia mouse model
dc.creator.none.fl_str_mv Kossatz, Elk
Maldonado, Rafael, 1961-
Robledo, Patricia, 1958-
author Kossatz, Elk
author_facet Kossatz, Elk
Maldonado, Rafael, 1961-
Robledo, Patricia, 1958-
author_role author
author2 Maldonado, Rafael, 1961-
Robledo, Patricia, 1958-
author2_role author
author
dc.subject.none.fl_str_mv Cervell -- Ferides i lesions
Isquèmia
Anoxèmia
Cannabinoides -- Receptors
topic Cervell -- Ferides i lesions
Isquèmia
Anoxèmia
Cannabinoides -- Receptors
description The role of CB2 cannabinoid receptors (CB2R) in global brain lesions induced by hypoxia-ischemia (HI) insult is still unresolved. The aim of this study was to evaluate the involvement of CB2R in the behavioural and biochemical underpinnings related to brain damage induced by HI in adult mice, and the mechanisms involved. CB2R knockout (KO) mice and wild-type littermates (WT) underwent permanent ligation of the left common carotid artery and hypoxia. Behavioural measurements in the rotarod, beam walking, object recognition, open field, and Irwin tests were carried out 24h, 72h and 7 days. In KO mice, more extensive brain injury was observed. Behavioural deficits in the Irwin test were observed in both genotypes; while WT mice showed progressive recovery by day 7, KO mice did not. Only KO mice showed alterations in motor learning, coordination and balance, and did not recover over time. A higher expression of microglia and astrocytes was observed in several brain areas of lesioned WT and KO mice. The possible alteration of the inflammatory-related factors HIF-1α and TIM-3 was evaluated in these animals. In both genotypes, HIF-1α and TIM-3 expression was observed in lesioned areas associated with activated microglia. However, the expression levels of these proteins were exacerbated in KO mice in several lesioned and non-lesioned brain structures. Our results indicate that CB2R may have a crucial neuroprotective role following HI insult through the modulation of the inflammatory-related HIF-1α/TIM-3 signalling pathway in microglia.
publishDate 2016
dc.date.none.fl_str_mv 2016
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/30847
http://dx.doi.org/10.1016/j.euroneuro.2016.10.003
url http://hdl.handle.net/10230/30847
http://dx.doi.org/10.1016/j.euroneuro.2016.10.003
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv European Neuropsychopharmacology. 2016 Dec;26(12):1972-88
info:eu-repo/grantAgreement/EC/FP7/602891
info:eu-repo/grantAgreement/ES/1PE/SAF2014-59648-P
dc.rights.none.fl_str_mv © Elsevier http://dx.doi.org/10.1016/j.euroneuro.2016.10.003
info:eu-repo/semantics/openAccess
rights_invalid_str_mv © Elsevier http://dx.doi.org/10.1016/j.euroneuro.2016.10.003
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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