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

Reactive astrogliosis, a complex process characterized by cell hypertrophy and upregulation of components of intermediate filaments, is a common feature in brains of Alzheimer's patients. Reactive astrocytes are found in close association with neuritic plaques; however, the precise role of thes...

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Autores: Gomez-Arboledas, Angela, Davila, Jose C, Sanchez-Mejias, Elisabeth, Navarro, Victoria, Nuñez-Diaz, Cristina, Sanchez-Varo, Raquel, Sanchez-Mico, Maria Virtudes, Trujillo-Estrada, Laura, Fernandez-Valenzuela, Juan Jose, Vizuete, Marisa, Comella, Joan X, Galea, Elena, Vitorica, Javier, Gutierrez, Antonia
Formato: artículo
Fecha de publicación:2017
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/17349
Acesso em linha:http://hdl.handle.net/20.500.12105/17349
Access Level:acceso abierto
Palavra-chave:Alzheimer's disease
neurodegeneration
neuropathology
reactive astrocyte
synaptopathy
Alzheimer Disease
Amyloid beta-Protein Precursor
Animals
Astrocytes
Disease Models, Animal
Hippocampus
Humans
Male
Mice, Inbred C57BL
Mice, Transgenic
Microglia
Phagocytosis
Plaque, Amyloid
Presenilin-1
Synapses
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spelling Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease.Gomez-Arboledas, AngelaDavila, Jose CSanchez-Mejias, ElisabethNavarro, VictoriaNuñez-Diaz, CristinaSanchez-Varo, RaquelSanchez-Mico, Maria VirtudesTrujillo-Estrada, LauraFernandez-Valenzuela, Juan JoseVizuete, MarisaComella, Joan XGalea, ElenaVitorica, JavierGutierrez, AntoniaAlzheimer's diseaseneurodegenerationneuropathologyreactive astrocytesynaptopathyAlzheimer DiseaseAmyloid beta-Protein PrecursorAnimalsAstrocytesDisease Models, AnimalHippocampusHumansMaleMice, Inbred C57BLMice, TransgenicMicrogliaPhagocytosisPlaque, AmyloidPresenilin-1SynapsesReactive astrogliosis, a complex process characterized by cell hypertrophy and upregulation of components of intermediate filaments, is a common feature in brains of Alzheimer's patients. Reactive astrocytes are found in close association with neuritic plaques; however, the precise role of these glial cells in disease pathogenesis is unknown. In this study, using immunohistochemical techniques and light and electron microscopy, we report that plaque-associated reactive astrocytes enwrap, engulf and may digest presynaptic dystrophies in the hippocampus of amyloid precursor protein/presenilin-1 (APP/PS1) mice. Microglia, the brain phagocytic population, was apparently not engaged in this clearance. Phagocytic reactive astrocytes were present in 35% and 67% of amyloid plaques at 6 and 12 months of age, respectively. The proportion of engulfed dystrophic neurites was low, around 7% of total dystrophies around plaques at both ages. This fact, along with the accumulation of dystrophic neurites during disease course, suggests that the efficiency of the astrocyte phagocytic process might be limited or impaired. Reactive astrocytes surrounding and engulfing dystrophic neurites were also detected in the hippocampus of Alzheimer's patients by confocal and ultrastructural analysis. We posit that the phagocytic activity of reactive astrocytes might contribute to clear dysfunctional synapses or synaptic debris, thereby restoring impaired neural circuits and reducing the inflammatory impact of damaged neuronal parts and/or limiting the amyloid pathology. Therefore, potentiation of the phagocytic properties of reactive astrocytes may represent a potential therapy in Alzheimer's disease.20242024-01-2320172017-11-2720172017-11-27research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articlehttp://hdl.handle.net/20.500.12105/17349reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/173492026-06-12T12:43:37Z
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.
Gomez-Arboledas, Angela
Alzheimer's disease
neurodegeneration
neuropathology
reactive astrocyte
synaptopathy
Alzheimer Disease
Amyloid beta-Protein Precursor
Animals
Astrocytes
Disease Models, Animal
Hippocampus
Humans
Male
Mice, Inbred C57BL
Mice, Transgenic
Microglia
Phagocytosis
Plaque, Amyloid
Presenilin-1
Synapses
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 Gomez-Arboledas, Angela
Davila, Jose C
Sanchez-Mejias, Elisabeth
Navarro, Victoria
Nuñez-Diaz, Cristina
Sanchez-Varo, Raquel
Sanchez-Mico, Maria Virtudes
Trujillo-Estrada, Laura
Fernandez-Valenzuela, Juan Jose
Vizuete, Marisa
Comella, Joan X
Galea, Elena
Vitorica, Javier
Gutierrez, Antonia
author Gomez-Arboledas, Angela
author_facet Gomez-Arboledas, Angela
Davila, Jose C
Sanchez-Mejias, Elisabeth
Navarro, Victoria
Nuñez-Diaz, Cristina
Sanchez-Varo, Raquel
Sanchez-Mico, Maria Virtudes
Trujillo-Estrada, Laura
Fernandez-Valenzuela, Juan Jose
Vizuete, Marisa
Comella, Joan X
Galea, Elena
Vitorica, Javier
Gutierrez, Antonia
author_role author
author2 Davila, Jose C
Sanchez-Mejias, Elisabeth
Navarro, Victoria
Nuñez-Diaz, Cristina
Sanchez-Varo, Raquel
Sanchez-Mico, Maria Virtudes
Trujillo-Estrada, Laura
Fernandez-Valenzuela, Juan Jose
Vizuete, Marisa
Comella, Joan X
Galea, Elena
Vitorica, Javier
Gutierrez, Antonia
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Alzheimer's disease
neurodegeneration
neuropathology
reactive astrocyte
synaptopathy
Alzheimer Disease
Amyloid beta-Protein Precursor
Animals
Astrocytes
Disease Models, Animal
Hippocampus
Humans
Male
Mice, Inbred C57BL
Mice, Transgenic
Microglia
Phagocytosis
Plaque, Amyloid
Presenilin-1
Synapses
topic Alzheimer's disease
neurodegeneration
neuropathology
reactive astrocyte
synaptopathy
Alzheimer Disease
Amyloid beta-Protein Precursor
Animals
Astrocytes
Disease Models, Animal
Hippocampus
Humans
Male
Mice, Inbred C57BL
Mice, Transgenic
Microglia
Phagocytosis
Plaque, Amyloid
Presenilin-1
Synapses
description Reactive astrogliosis, a complex process characterized by cell hypertrophy and upregulation of components of intermediate filaments, is a common feature in brains of Alzheimer's patients. Reactive astrocytes are found in close association with neuritic plaques; however, the precise role of these glial cells in disease pathogenesis is unknown. In this study, using immunohistochemical techniques and light and electron microscopy, we report that plaque-associated reactive astrocytes enwrap, engulf and may digest presynaptic dystrophies in the hippocampus of amyloid precursor protein/presenilin-1 (APP/PS1) mice. Microglia, the brain phagocytic population, was apparently not engaged in this clearance. Phagocytic reactive astrocytes were present in 35% and 67% of amyloid plaques at 6 and 12 months of age, respectively. The proportion of engulfed dystrophic neurites was low, around 7% of total dystrophies around plaques at both ages. This fact, along with the accumulation of dystrophic neurites during disease course, suggests that the efficiency of the astrocyte phagocytic process might be limited or impaired. Reactive astrocytes surrounding and engulfing dystrophic neurites were also detected in the hippocampus of Alzheimer's patients by confocal and ultrastructural analysis. We posit that the phagocytic activity of reactive astrocytes might contribute to clear dysfunctional synapses or synaptic debris, thereby restoring impaired neural circuits and reducing the inflammatory impact of damaged neuronal parts and/or limiting the amyloid pathology. Therefore, potentiation of the phagocytic properties of reactive astrocytes may represent a potential therapy in Alzheimer's disease.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-11-27
2017
2017-11-27
2024
2024-01-23
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/17349
url http://hdl.handle.net/20.500.12105/17349
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.81155

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