I2 imidazoline receptor modulation protects aged SAMP8 mice against cognitive decline by suppressing the calcineurin pathway

Brain aging and dementia are current problems that must be solved. The levels of imidazoline 2 receptors (I2-IRs) are increased in the brain in Alzheimer's disease (AD) and other neurodegenerative diseases. We tested the action of the specific and selective I2-IR ligand B06 in a mouse model of...

ver descrição completa

Detalhes bibliográficos
Autores: Vasilopoulou, Foteini, Griñán Ferré, Christian, Rodríguez-Arévalo, Sergio, Bagan Polonio, Andrea, Escolano Mirón, Carmen, Pallàs i Llibería, Mercè, 1964-
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2020
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/174256
Acesso em linha:https://hdl.handle.net/2445/174256
Access Level:acceso abierto
Palavra-chave:Demència
Envelliment cerebral
Malaltia d'Alzheimer
Malalties neurodegeneratives
Dementia
Aging brain
Alzheimer's disease
Neurodegenerative Diseases
id ES_7322ead048c2fcd65c20adbb184d645b
oai_identifier_str oai:recercat.cat:2445/174256
network_acronym_str ES
network_name_str España
repository_id_str
spelling I2 imidazoline receptor modulation protects aged SAMP8 mice against cognitive decline by suppressing the calcineurin pathwayVasilopoulou, FoteiniGriñán Ferré, ChristianRodríguez-Arévalo, SergioBagan Polonio, AndreaEscolano Mirón, CarmenPallàs i Llibería, Mercè, 1964-DemènciaEnvelliment cerebralMalaltia d'AlzheimerMalalties neurodegenerativesDementiaAging brainAlzheimer's diseaseNeurodegenerative DiseasesBrain aging and dementia are current problems that must be solved. The levels of imidazoline 2 receptors (I2-IRs) are increased in the brain in Alzheimer's disease (AD) and other neurodegenerative diseases. We tested the action of the specific and selective I2-IR ligand B06 in a mouse model of accelerated aging and AD, the senescence-accelerated mouse prone 8 (SAMP8) model. Oral administration of B06 for 4 weeks improved SAMP8 mouse behavior and cognition and reduced AD hallmarks, oxidative stress, and apoptotic and neuroinflammation markers. Likewise, B06 regulated glial excitatory amino acid transporter 2 and N-methyl-D aspartate 2A and 2B receptor subunit protein levels. Calcineurin (CaN) is a phosphatase that controls the phosphorylation levels of cAMP response element-binding (CREB), apoptotic mediator BCL-2-associated agonist of cell death (BAD) and GSK3β, among other molecules. Interestingly, B06 was able to reduce the levels of the CaN active form (CaN A). Likewise, CREB phosphorylation, BAD gene expression, and other factors were modified after B06 treatment. Moreover, phosphorylation of a target of CaN, nuclear factor of activated Tcells, cytoplasmic 1 (NFATC1), was increased in B06- treated mice, impeding the transcription of genes related to neuroinflammation and neural plasticity. In summary, this I2 imidazoline ligand can exert its beneficial effects on age-related conditions by modulating CaN pathway action and affecting several molecular pathways, playing a neuroprotective role in SAMP8Springer Nature2021202120202021info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/174256Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)CatalánVersió postprint del document publicat a: https://doi.org/10.1007/s11357-020-00281-2Geroscience, 2020https://doi.org/10.1007/s11357-020-00281-2(c) American Aging Association, 2020info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1742562026-05-29T05:05:01Z
dc.title.none.fl_str_mv I2 imidazoline receptor modulation protects aged SAMP8 mice against cognitive decline by suppressing the calcineurin pathway
title I2 imidazoline receptor modulation protects aged SAMP8 mice against cognitive decline by suppressing the calcineurin pathway
spellingShingle I2 imidazoline receptor modulation protects aged SAMP8 mice against cognitive decline by suppressing the calcineurin pathway
Vasilopoulou, Foteini
Demència
Envelliment cerebral
Malaltia d'Alzheimer
Malalties neurodegeneratives
Dementia
Aging brain
Alzheimer's disease
Neurodegenerative Diseases
title_short I2 imidazoline receptor modulation protects aged SAMP8 mice against cognitive decline by suppressing the calcineurin pathway
title_full I2 imidazoline receptor modulation protects aged SAMP8 mice against cognitive decline by suppressing the calcineurin pathway
title_fullStr I2 imidazoline receptor modulation protects aged SAMP8 mice against cognitive decline by suppressing the calcineurin pathway
title_full_unstemmed I2 imidazoline receptor modulation protects aged SAMP8 mice against cognitive decline by suppressing the calcineurin pathway
title_sort I2 imidazoline receptor modulation protects aged SAMP8 mice against cognitive decline by suppressing the calcineurin pathway
dc.creator.none.fl_str_mv Vasilopoulou, Foteini
Griñán Ferré, Christian
Rodríguez-Arévalo, Sergio
Bagan Polonio, Andrea
Escolano Mirón, Carmen
Pallàs i Llibería, Mercè, 1964-
author Vasilopoulou, Foteini
author_facet Vasilopoulou, Foteini
Griñán Ferré, Christian
Rodríguez-Arévalo, Sergio
Bagan Polonio, Andrea
Escolano Mirón, Carmen
Pallàs i Llibería, Mercè, 1964-
author_role author
author2 Griñán Ferré, Christian
Rodríguez-Arévalo, Sergio
Bagan Polonio, Andrea
Escolano Mirón, Carmen
Pallàs i Llibería, Mercè, 1964-
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Demència
Envelliment cerebral
Malaltia d'Alzheimer
Malalties neurodegeneratives
Dementia
Aging brain
Alzheimer's disease
Neurodegenerative Diseases
topic Demència
Envelliment cerebral
Malaltia d'Alzheimer
Malalties neurodegeneratives
Dementia
Aging brain
Alzheimer's disease
Neurodegenerative Diseases
description Brain aging and dementia are current problems that must be solved. The levels of imidazoline 2 receptors (I2-IRs) are increased in the brain in Alzheimer's disease (AD) and other neurodegenerative diseases. We tested the action of the specific and selective I2-IR ligand B06 in a mouse model of accelerated aging and AD, the senescence-accelerated mouse prone 8 (SAMP8) model. Oral administration of B06 for 4 weeks improved SAMP8 mouse behavior and cognition and reduced AD hallmarks, oxidative stress, and apoptotic and neuroinflammation markers. Likewise, B06 regulated glial excitatory amino acid transporter 2 and N-methyl-D aspartate 2A and 2B receptor subunit protein levels. Calcineurin (CaN) is a phosphatase that controls the phosphorylation levels of cAMP response element-binding (CREB), apoptotic mediator BCL-2-associated agonist of cell death (BAD) and GSK3β, among other molecules. Interestingly, B06 was able to reduce the levels of the CaN active form (CaN A). Likewise, CREB phosphorylation, BAD gene expression, and other factors were modified after B06 treatment. Moreover, phosphorylation of a target of CaN, nuclear factor of activated Tcells, cytoplasmic 1 (NFATC1), was increased in B06- treated mice, impeding the transcription of genes related to neuroinflammation and neural plasticity. In summary, this I2 imidazoline ligand can exert its beneficial effects on age-related conditions by modulating CaN pathway action and affecting several molecular pathways, playing a neuroprotective role in SAMP8
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
2021
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 https://hdl.handle.net/2445/174256
url https://hdl.handle.net/2445/174256
dc.language.none.fl_str_mv Catalán
language_invalid_str_mv Catalán
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1007/s11357-020-00281-2
Geroscience, 2020
https://doi.org/10.1007/s11357-020-00281-2
dc.rights.none.fl_str_mv (c) American Aging Association, 2020
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Aging Association, 2020
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869410787299164160
score 15,198674

Registos relacionados