Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease

Reactive astrogliosis, a complex process characterized by cell hypertrophy and upregulation ofcomponents of intermediate filaments, is a common feature in brains of Alzheimer’s patients. Reac-tive astrocytes are found in close association with neuritic plaques; however, the precise role ofthese glia...

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Autores: Gómez Arboledas, Ángela, Dávila Cansino, José Carlos, Sánchez Mejías, Elisabeth, Navarro Garrido, Victoria, Núñez Díaz, Cristina, Sánchez Varo, Raquel María, Sánchez Mico, María, Vizuete Chacón, María Luisa, Vitorica Ferrández, Francisco Javier, Gutiérrez Pérez, Antonia
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Recursos:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/135193
Acesso em linha:https://hdl.handle.net/11441/135193
https://doi.org/10.1002/glia.23270
Access Level:acceso abierto
Palavra-chave:Alzheimer’s disease
neurodegeneration
neuropathology
reactive astrocyte
synaptopathy
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spelling Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's diseaseGómez Arboledas, ÁngelaDávila Cansino, José CarlosSánchez Mejías, ElisabethNavarro Garrido, VictoriaNúñez Díaz, CristinaSánchez Varo, Raquel MaríaSánchez Mico, MaríaVizuete Chacón, María LuisaVitorica Ferrández, Francisco JavierGutiérrez Pérez, AntoniaAlzheimer’s diseaseneurodegenerationneuropathologyreactive astrocytesynaptopathyReactive astrogliosis, a complex process characterized by cell hypertrophy and upregulation ofcomponents of intermediate filaments, is a common feature in brains of Alzheimer’s patients. Reac-tive astrocytes are found in close association with neuritic plaques; however, the precise role ofthese glial cells in disease pathogenesis is unknown. In this study, using immunohistochemical tech-niques and light and electron microscopy, we report that plaque-associated reactive astrocytesenwrap, engulf and may digest presynaptic dystrophies in the hippocampus of amyloid precursorprotein/presenilin-1 (APP/PS1) mice. Microglia, the brain phagocytic population, was apparentlynot engaged in this clearance. Phagocytic reactive astrocytes were present in 35% and 67% ofamyloid plaques at 6 and 12 months of age, respectively. The proportion of engulfed dystrophicneurites was low, around 7% of total dystrophies around plaques at both ages. This fact, alongwith the accumulation of dystrophic neurites during disease course, suggests that the efficiency ofthe astrocyte phagocytic process might be limited or impaired. Reactive astrocytes surroundingand engulfing dystrophic neurites were also detected in the hippocampus of Alzheimer’spatientsby confocal and ultrastructural analysis. We posit that the phagocytic activity of reactive astrocytesmight contribute to clear dysfunctional synapses or synaptic debris, thereby restoring impairedneural circuits and reducing the inflammatory impact of damaged neuronal parts and/or limitingthe amyloid pathology. Therefore, potentiation of the phagocytic properties of reactive astrocytesmay represent a potential therapy in Alzheimer s disease.Fondo de Investigación Sanitaria (FIS). Instituto de Salud Carlos III (ISCiii) de España y fondos FEDER de la Unión Europea. PI15/00796 y PI15/00957Fundación La Marató-TV3 de Cataluña, España. 20141432, 20141431, 20141433, y 20141430Centro de investigación en red de enfermedades neurodegenerativas (CIBERNED) de España. PI2015-2/02Junta de Andalucía. Proyecto de Excelencia CTS-2035WileyBioquímica y Biología MolecularInstituto de Salud Carlos IIIEuropean Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)Fundación La Marató-TV3. Cataluña. EspañaJunta de Andalucía2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/135193https://doi.org/10.1002/glia.23270reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésGlia, 66 (3), 637-653.PI15/00796PI15/00957CTS-2035https://doi.org/10.1002/glia.23270info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1351932026-06-17T12:51:07Z
dc.title.none.fl_str_mv Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease
title Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease
spellingShingle Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease
Gómez Arboledas, Ángela
Alzheimer’s disease
neurodegeneration
neuropathology
reactive astrocyte
synaptopathy
title_short Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease
title_full Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease
title_fullStr Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease
title_full_unstemmed Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease
title_sort Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease
dc.creator.none.fl_str_mv Gómez Arboledas, Ángela
Dávila Cansino, José Carlos
Sánchez Mejías, Elisabeth
Navarro Garrido, Victoria
Núñez Díaz, Cristina
Sánchez Varo, Raquel María
Sánchez Mico, María
Vizuete Chacón, María Luisa
Vitorica Ferrández, Francisco Javier
Gutiérrez Pérez, Antonia
author Gómez Arboledas, Ángela
author_facet Gómez Arboledas, Ángela
Dávila Cansino, José Carlos
Sánchez Mejías, Elisabeth
Navarro Garrido, Victoria
Núñez Díaz, Cristina
Sánchez Varo, Raquel María
Sánchez Mico, María
Vizuete Chacón, María Luisa
Vitorica Ferrández, Francisco Javier
Gutiérrez Pérez, Antonia
author_role author
author2 Dávila Cansino, José Carlos
Sánchez Mejías, Elisabeth
Navarro Garrido, Victoria
Núñez Díaz, Cristina
Sánchez Varo, Raquel María
Sánchez Mico, María
Vizuete Chacón, María Luisa
Vitorica Ferrández, Francisco Javier
Gutiérrez Pérez, Antonia
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Bioquímica y Biología Molecular
Instituto de Salud Carlos III
European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
Fundación La Marató-TV3. Cataluña. España
Junta de Andalucía
dc.subject.none.fl_str_mv Alzheimer’s disease
neurodegeneration
neuropathology
reactive astrocyte
synaptopathy
topic Alzheimer’s disease
neurodegeneration
neuropathology
reactive astrocyte
synaptopathy
description Reactive astrogliosis, a complex process characterized by cell hypertrophy and upregulation ofcomponents of intermediate filaments, is a common feature in brains of Alzheimer’s patients. Reac-tive astrocytes are found in close association with neuritic plaques; however, the precise role ofthese glial cells in disease pathogenesis is unknown. In this study, using immunohistochemical tech-niques and light and electron microscopy, we report that plaque-associated reactive astrocytesenwrap, engulf and may digest presynaptic dystrophies in the hippocampus of amyloid precursorprotein/presenilin-1 (APP/PS1) mice. Microglia, the brain phagocytic population, was apparentlynot engaged in this clearance. Phagocytic reactive astrocytes were present in 35% and 67% ofamyloid plaques at 6 and 12 months of age, respectively. The proportion of engulfed dystrophicneurites was low, around 7% of total dystrophies around plaques at both ages. This fact, alongwith the accumulation of dystrophic neurites during disease course, suggests that the efficiency ofthe astrocyte phagocytic process might be limited or impaired. Reactive astrocytes surroundingand engulfing dystrophic neurites were also detected in the hippocampus of Alzheimer’spatientsby confocal and ultrastructural analysis. We posit that the phagocytic activity of reactive astrocytesmight contribute to clear dysfunctional synapses or synaptic debris, thereby restoring impairedneural circuits and reducing the inflammatory impact of damaged neuronal parts and/or limitingthe amyloid pathology. Therefore, potentiation of the phagocytic properties of reactive astrocytesmay represent a potential therapy in Alzheimer s disease.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/135193
https://doi.org/10.1002/glia.23270
url https://hdl.handle.net/11441/135193
https://doi.org/10.1002/glia.23270
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Glia, 66 (3), 637-653.
PI15/00796
PI15/00957
CTS-2035
https://doi.org/10.1002/glia.23270
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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