Unraveling the β-AMYLOID clearance by astrocytes: Involvement of metabotropic glutamate receptor 3, sAPPα, and class-A scavenger receptor

Autores
Durand, Daniela Elizabeth; Turati, Juan; Rudi, María Julieta; Ramírez, Delia; Saba, Julieta; Caruso, Carla Mariana; Carniglia, Lila; von Bernhardi, Rommy; Lasaga, Mercedes Isabel
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The mechanics of β-amyloid (Aβ) clearance by astrocytes has not been univocally described, with different mediators appearing to contribute to this process under different conditions. Our laboratory has demonstrated neuroprotective effects of astroglial subtype 3 metabotropic glutamate receptor (mGlu3R), which are dependent on the secreted form of the amyloid precursor protein (sAPPα) as well as on Aβ clearance; however, the mechanism underlying mGlu3R-induced Aβ uptake by astrocytes remains unclear. The present study shows that conditioned medium from mGlu3R-stimulated astrocytes increased Aβ uptake by naïve astrocytes through a mechanism dependent on sAPPα, since sAPPα depletion from conditioned medium inhibited Aβ phagocytosis. Concordantly, recombinant sAPPα also increased Aβ uptake. Since we show that both sAPPα and the mGlu3R agonist LY379268 increased expression of class-A scavenger receptor (SR-A) in astrocytes, we next determined whether SR-A mediates mGlu3R- or sAPPα-induced Aβ uptake by using astrocyte cultures derived from SR-A knockout mice. We found that the effects of LY379268 as well as sAPPα on Aβ uptake were abolished in SR-A-deficient astrocytes, indicating a major role for this scavenger receptor in LY379268- and sAPPα-stimulated Aβ clearance by astrocytes. We also show results of coimmunoprecipitation and functional assays offering evidence of possible heterotrimerization of sAPPα with Aβ and SR-A which could allow Aβ to enter the astrocyte. In conclusion the present paper describes a novel pathway for Aβ clearance by astrocytes involving sAPPα as an enhancer of SR-A-dependent Aβ phagocytosis.
Fil: Durand, Daniela Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Turati, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Rudi, María Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Ramírez, Delia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Saba, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Caruso, Carla Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Carniglia, Lila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: von Bernhardi, Rommy. Pontificia Universidad Católica de Chile; Chile
Fil: Lasaga, Mercedes Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Materia
ASTROCYTES
mGlu3R
sAPP ALPHA
AMYLOID CLEARANCE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/113666
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/113666
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Unraveling the β-AMYLOID clearance by astrocytes: Involvement of metabotropic glutamate receptor 3, sAPPα, and class-A scavenger receptorDurand, Daniela ElizabethTurati, JuanRudi, María JulietaRamírez, DeliaSaba, JulietaCaruso, Carla MarianaCarniglia, Lilavon Bernhardi, RommyLasaga, Mercedes IsabelASTROCYTESmGlu3RsAPP ALPHAAMYLOID CLEARANCEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The mechanics of β-amyloid (Aβ) clearance by astrocytes has not been univocally described, with different mediators appearing to contribute to this process under different conditions. Our laboratory has demonstrated neuroprotective effects of astroglial subtype 3 metabotropic glutamate receptor (mGlu3R), which are dependent on the secreted form of the amyloid precursor protein (sAPPα) as well as on Aβ clearance; however, the mechanism underlying mGlu3R-induced Aβ uptake by astrocytes remains unclear. The present study shows that conditioned medium from mGlu3R-stimulated astrocytes increased Aβ uptake by naïve astrocytes through a mechanism dependent on sAPPα, since sAPPα depletion from conditioned medium inhibited Aβ phagocytosis. Concordantly, recombinant sAPPα also increased Aβ uptake. Since we show that both sAPPα and the mGlu3R agonist LY379268 increased expression of class-A scavenger receptor (SR-A) in astrocytes, we next determined whether SR-A mediates mGlu3R- or sAPPα-induced Aβ uptake by using astrocyte cultures derived from SR-A knockout mice. We found that the effects of LY379268 as well as sAPPα on Aβ uptake were abolished in SR-A-deficient astrocytes, indicating a major role for this scavenger receptor in LY379268- and sAPPα-stimulated Aβ clearance by astrocytes. We also show results of coimmunoprecipitation and functional assays offering evidence of possible heterotrimerization of sAPPα with Aβ and SR-A which could allow Aβ to enter the astrocyte. In conclusion the present paper describes a novel pathway for Aβ clearance by astrocytes involving sAPPα as an enhancer of SR-A-dependent Aβ phagocytosis.Fil: Durand, Daniela Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Turati, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Rudi, María Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Ramírez, Delia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Saba, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Caruso, Carla Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Carniglia, Lila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: von Bernhardi, Rommy. Pontificia Universidad Católica de Chile; ChileFil: Lasaga, Mercedes Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaElsevier2019-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/113666Durand, Daniela Elizabeth; Turati, Juan; Rudi, María Julieta; Ramírez, Delia; Saba, Julieta; et al.; Unraveling the β-AMYLOID clearance by astrocytes: Involvement of metabotropic glutamate receptor 3, sAPPα, and class-A scavenger receptor; Elsevier; Neurochemistry International; 131; 12-2019; 1-9; 1045470197-01861872-9754CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0197018619304656info:eu-repo/semantics/altIdentifier/doi/10.1016/j.neuint.2019.104547info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:17:25Zoai:ri.conicet.gov.ar:11336/113666instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:17:25.551CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Unraveling the β-AMYLOID clearance by astrocytes: Involvement of metabotropic glutamate receptor 3, sAPPα, and class-A scavenger receptor
title Unraveling the β-AMYLOID clearance by astrocytes: Involvement of metabotropic glutamate receptor 3, sAPPα, and class-A scavenger receptor
spellingShingle Unraveling the β-AMYLOID clearance by astrocytes: Involvement of metabotropic glutamate receptor 3, sAPPα, and class-A scavenger receptor
Durand, Daniela Elizabeth
ASTROCYTES
mGlu3R
sAPP ALPHA
AMYLOID CLEARANCE
title_short Unraveling the β-AMYLOID clearance by astrocytes: Involvement of metabotropic glutamate receptor 3, sAPPα, and class-A scavenger receptor
title_full Unraveling the β-AMYLOID clearance by astrocytes: Involvement of metabotropic glutamate receptor 3, sAPPα, and class-A scavenger receptor
title_fullStr Unraveling the β-AMYLOID clearance by astrocytes: Involvement of metabotropic glutamate receptor 3, sAPPα, and class-A scavenger receptor
title_full_unstemmed Unraveling the β-AMYLOID clearance by astrocytes: Involvement of metabotropic glutamate receptor 3, sAPPα, and class-A scavenger receptor
title_sort Unraveling the β-AMYLOID clearance by astrocytes: Involvement of metabotropic glutamate receptor 3, sAPPα, and class-A scavenger receptor
dc.creator.none.fl_str_mv Durand, Daniela Elizabeth
Turati, Juan
Rudi, María Julieta
Ramírez, Delia
Saba, Julieta
Caruso, Carla Mariana
Carniglia, Lila
von Bernhardi, Rommy
Lasaga, Mercedes Isabel
author Durand, Daniela Elizabeth
author_facet Durand, Daniela Elizabeth
Turati, Juan
Rudi, María Julieta
Ramírez, Delia
Saba, Julieta
Caruso, Carla Mariana
Carniglia, Lila
von Bernhardi, Rommy
Lasaga, Mercedes Isabel
author_role author
author2 Turati, Juan
Rudi, María Julieta
Ramírez, Delia
Saba, Julieta
Caruso, Carla Mariana
Carniglia, Lila
von Bernhardi, Rommy
Lasaga, Mercedes Isabel
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ASTROCYTES
mGlu3R
sAPP ALPHA
AMYLOID CLEARANCE
topic ASTROCYTES
mGlu3R
sAPP ALPHA
AMYLOID CLEARANCE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The mechanics of β-amyloid (Aβ) clearance by astrocytes has not been univocally described, with different mediators appearing to contribute to this process under different conditions. Our laboratory has demonstrated neuroprotective effects of astroglial subtype 3 metabotropic glutamate receptor (mGlu3R), which are dependent on the secreted form of the amyloid precursor protein (sAPPα) as well as on Aβ clearance; however, the mechanism underlying mGlu3R-induced Aβ uptake by astrocytes remains unclear. The present study shows that conditioned medium from mGlu3R-stimulated astrocytes increased Aβ uptake by naïve astrocytes through a mechanism dependent on sAPPα, since sAPPα depletion from conditioned medium inhibited Aβ phagocytosis. Concordantly, recombinant sAPPα also increased Aβ uptake. Since we show that both sAPPα and the mGlu3R agonist LY379268 increased expression of class-A scavenger receptor (SR-A) in astrocytes, we next determined whether SR-A mediates mGlu3R- or sAPPα-induced Aβ uptake by using astrocyte cultures derived from SR-A knockout mice. We found that the effects of LY379268 as well as sAPPα on Aβ uptake were abolished in SR-A-deficient astrocytes, indicating a major role for this scavenger receptor in LY379268- and sAPPα-stimulated Aβ clearance by astrocytes. We also show results of coimmunoprecipitation and functional assays offering evidence of possible heterotrimerization of sAPPα with Aβ and SR-A which could allow Aβ to enter the astrocyte. In conclusion the present paper describes a novel pathway for Aβ clearance by astrocytes involving sAPPα as an enhancer of SR-A-dependent Aβ phagocytosis.
Fil: Durand, Daniela Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Turati, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Rudi, María Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Ramírez, Delia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Saba, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Caruso, Carla Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Carniglia, Lila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: von Bernhardi, Rommy. Pontificia Universidad Católica de Chile; Chile
Fil: Lasaga, Mercedes Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
description The mechanics of β-amyloid (Aβ) clearance by astrocytes has not been univocally described, with different mediators appearing to contribute to this process under different conditions. Our laboratory has demonstrated neuroprotective effects of astroglial subtype 3 metabotropic glutamate receptor (mGlu3R), which are dependent on the secreted form of the amyloid precursor protein (sAPPα) as well as on Aβ clearance; however, the mechanism underlying mGlu3R-induced Aβ uptake by astrocytes remains unclear. The present study shows that conditioned medium from mGlu3R-stimulated astrocytes increased Aβ uptake by naïve astrocytes through a mechanism dependent on sAPPα, since sAPPα depletion from conditioned medium inhibited Aβ phagocytosis. Concordantly, recombinant sAPPα also increased Aβ uptake. Since we show that both sAPPα and the mGlu3R agonist LY379268 increased expression of class-A scavenger receptor (SR-A) in astrocytes, we next determined whether SR-A mediates mGlu3R- or sAPPα-induced Aβ uptake by using astrocyte cultures derived from SR-A knockout mice. We found that the effects of LY379268 as well as sAPPα on Aβ uptake were abolished in SR-A-deficient astrocytes, indicating a major role for this scavenger receptor in LY379268- and sAPPα-stimulated Aβ clearance by astrocytes. We also show results of coimmunoprecipitation and functional assays offering evidence of possible heterotrimerization of sAPPα with Aβ and SR-A which could allow Aβ to enter the astrocyte. In conclusion the present paper describes a novel pathway for Aβ clearance by astrocytes involving sAPPα as an enhancer of SR-A-dependent Aβ phagocytosis.
publishDate 2019
dc.date.none.fl_str_mv 2019-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/113666
Durand, Daniela Elizabeth; Turati, Juan; Rudi, María Julieta; Ramírez, Delia; Saba, Julieta; et al.; Unraveling the β-AMYLOID clearance by astrocytes: Involvement of metabotropic glutamate receptor 3, sAPPα, and class-A scavenger receptor; Elsevier; Neurochemistry International; 131; 12-2019; 1-9; 104547
0197-0186
1872-9754
CONICET Digital
CONICET
url http://hdl.handle.net/11336/113666
identifier_str_mv Durand, Daniela Elizabeth; Turati, Juan; Rudi, María Julieta; Ramírez, Delia; Saba, Julieta; et al.; Unraveling the β-AMYLOID clearance by astrocytes: Involvement of metabotropic glutamate receptor 3, sAPPα, and class-A scavenger receptor; Elsevier; Neurochemistry International; 131; 12-2019; 1-9; 104547
0197-0186
1872-9754
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0197018619304656
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.neuint.2019.104547
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
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:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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