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dc.contributor.author
Durand, Daniela Elizabeth
dc.contributor.author
Carniglia, Lila
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Turati, Juan
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Ramírez, Delia
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Saba, Julieta
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Caruso, Carla Mariana
dc.contributor.author
Lasaga, Mercedes Isabel
dc.date.available
2019-01-09T20:04:29Z
dc.date.issued
2017-09
dc.identifier.citation
Durand, Daniela Elizabeth; Carniglia, Lila; Turati, Juan; Ramírez, Delia; Saba, Julieta; et al.; Amyloid-beta neurotoxicity and clearance are both regulated by glial group II metabotropic glutamate receptors; Pergamon-Elsevier Science Ltd; Neuropharmacology; 123; 9-2017; 274-286
dc.identifier.issn
0028-3908
dc.identifier.uri
http://hdl.handle.net/11336/67832
dc.description.abstract
Astrocytes are now fully endorsed as key players in CNS functionality and plasticity. We recently showed that metabotropic glutamate receptor 3 (mGlu3R) activation by LY379268 promotes non-amyloidogenic cleavage of amyloid precursor protein (APP) in cultured astrocytes, leading to increased release of neuroprotective sAPPα. Furthermore, mGlu3R expression is reduced in hippocampal astrocytes from PDAPP-J20 mice, suggesting a role for these receptors in Alzheimer's disease. The present study enquires into the role of astroglial-derived neurotrophins induced by mGlu3R activation in neurotoxicity triggered by amyloid β (Aβ). Conditioned medium from LY379268-treated astrocytes protected hippocampal neurons from Aβ-induced cell death. Immunodepletion of sAPPα from the conditioned medium prevented its protective effect. LY379268 induced brain-derived neurotrophic factor (BDNF) expression in astrocytes, and neutralizing BDNF from conditioned medium also prevented its neuroprotective effect on Aβ neurotoxicity. LY379268 was also able to decrease Aβ-induced neuron death by acting directly on neuronal mGlu3R. On the other hand, LY379268 increased Aβ uptake in astrocytes and microglia. Indeed, and more importantly, a reduction in Aβ-induced neuron death was observed when co-cultured with LY379268-pretreated astrocytes, suggesting a link between neuroprotection and increased glial phagocytic activity. Altogether, these results indicate a double function for glial mGlu3R activation against Aβ neurotoxicity: (i) it increases the release of protective neurotrophins such as sAPPα and BDNF, and (ii) it induces amyloid removal from extracellular space by glia-mediated phagocytosis.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Pergamon-Elsevier Science Ltd
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
Alzheimer'S Disease
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Amyloid Β Clearance
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Bdnf
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Metabotropic Glutamate Receptors
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Neuron-Glia Interaction
dc.subject
SappΑ
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Neurociencias
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Amyloid-beta neurotoxicity and clearance are both regulated by glial group II metabotropic glutamate receptors
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-06T13:45:00Z
dc.journal.volume
123
dc.journal.pagination
274-286
dc.journal.pais
Estados Unidos
dc.description.fil
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
dc.description.fil
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
dc.description.fil
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
dc.description.fil
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
dc.description.fil
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
dc.description.fil
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
dc.description.fil
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
dc.journal.title
Neuropharmacology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.neuropharm.2017.05.008
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0028390817302046
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