Microglial Hemoxygenase-1 Deletion Reduces Inflammation in the Retina of Old Mice with Tauopathy

Tauopathies such as Alzheimer’s disease are characterized by the accumulation of neurotoxic aggregates of tau protein. With aging and, especially, in Alzheimer’s patients, the inducible enzyme heme oxygenase 1 (HO-1) progressively increases in microglia, causing iron accumulation, neuroinflammation,...

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Autores: Fernández Albarral, José, García Martín, Elena Salobrar, Matamoros Felipe, José Antonio, Fernández Mendivil, Cristina, Sastre, Eric, del, Chen, Leijing, Hoz Montañana, María Rosa De, López Cuenca, Inés, Sánchez-Puebla Fernández, Lidia, Ramírez Sebastián, José Manuel, Salazar Corral, Juan José, García López, Manuela, Ramírez Sebastián, Ana Isabel
Formato: artículo
Fecha de publicación:2022
País:España
Recursos:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/72797
Acesso em linha:https://hdl.handle.net/20.500.14352/72797
Access Level:acceso abierto
Palavra-chave:617.735
611.8.018.24
Tauopathies
Heme oxygenase 1 (HO-1)
Retina
Microglia
Macroglia
Neuroinflammation
Neurodegenerative diseases
Oftalmología
Anatomía ocular
Medicina
Neurociencias (Medicina)
3201.09 Oftalmología
32 Ciencias Médicas
2490 Neurociencias
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oai_identifier_str oai:docta.ucm.es:20.500.14352/72797
network_acronym_str ES
network_name_str España
repository_id_str
spelling Microglial Hemoxygenase-1 Deletion Reduces Inflammation in the Retina of Old Mice with TauopathyFernández Albarral, JoséGarcía Martín, Elena SalobrarMatamoros Felipe, José AntonioFernández Mendivil, CristinaSastre, Eric, delChen, LeijingHoz Montañana, María Rosa DeLópez Cuenca, InésSánchez-Puebla Fernández, LidiaRamírez Sebastián, José ManuelSalazar Corral, Juan JoséGarcía López, ManuelaRamírez Sebastián, Ana Isabel617.735611.8.018.24TauopathiesHeme oxygenase 1 (HO-1)RetinaMicrogliaMacrogliaNeuroinflammationNeurodegenerative diseasesOftalmologíaAnatomía ocularMedicinaNeurociencias (Medicina)3201.09 Oftalmología32 Ciencias Médicas2490 NeurocienciasTauopathies such as Alzheimer’s disease are characterized by the accumulation of neurotoxic aggregates of tau protein. With aging and, especially, in Alzheimer’s patients, the inducible enzyme heme oxygenase 1 (HO-1) progressively increases in microglia, causing iron accumulation, neuroinflammation, and neurodegeneration. The retina is an organ that can be readily accessed and can reflect changes that occur in the brain. In this context, we evaluated how the lack of microglial HO-1, using mice that do not express HO-1 in microglia (HMO-KO), impacts retinal macro and microgliosis of aged subjects (18 months old mice) subjected to tauopathy by intrahippocampal delivery of AAV-hTauP301L (TAU). Our results show that although tauopathy, measured as anti-TAUY9 and anti-AT8 positive immunostaining, was not observed in the retina of WT-TAU or HMO-KO+TAU mice, a morphometric study of retinal microglia and macroglia showed significant retinal changes in the TAU group compared to the WT group, such as: (i) increased number of activated microglia, (ii) retraction of microglial processes, (iii) increased number of CD68+ microglia, and (iv) increased retinal area occupied by GFAP (AROA) and C3 (AROC3). This retinal inflammatory profile was reduced in HMO-KO+TAU mice. Conclusion: Reduction of microglial HO-1 could be beneficial to prevent tauopathy-induced neuroinflammation.MDPIUniversidad Complutense de Madrid20222022-10-3020222022-10-30journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/72797reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttps://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/727972026-06-02T12:44:21Z
dc.title.none.fl_str_mv Microglial Hemoxygenase-1 Deletion Reduces Inflammation in the Retina of Old Mice with Tauopathy
title Microglial Hemoxygenase-1 Deletion Reduces Inflammation in the Retina of Old Mice with Tauopathy
spellingShingle Microglial Hemoxygenase-1 Deletion Reduces Inflammation in the Retina of Old Mice with Tauopathy
Fernández Albarral, José
617.735
611.8.018.24
Tauopathies
Heme oxygenase 1 (HO-1)
Retina
Microglia
Macroglia
Neuroinflammation
Neurodegenerative diseases
Oftalmología
Anatomía ocular
Medicina
Neurociencias (Medicina)
3201.09 Oftalmología
32 Ciencias Médicas
2490 Neurociencias
title_short Microglial Hemoxygenase-1 Deletion Reduces Inflammation in the Retina of Old Mice with Tauopathy
title_full Microglial Hemoxygenase-1 Deletion Reduces Inflammation in the Retina of Old Mice with Tauopathy
title_fullStr Microglial Hemoxygenase-1 Deletion Reduces Inflammation in the Retina of Old Mice with Tauopathy
title_full_unstemmed Microglial Hemoxygenase-1 Deletion Reduces Inflammation in the Retina of Old Mice with Tauopathy
title_sort Microglial Hemoxygenase-1 Deletion Reduces Inflammation in the Retina of Old Mice with Tauopathy
dc.creator.none.fl_str_mv Fernández Albarral, José
García Martín, Elena Salobrar
Matamoros Felipe, José Antonio
Fernández Mendivil, Cristina
Sastre, Eric, del
Chen, Leijing
Hoz Montañana, María Rosa De
López Cuenca, Inés
Sánchez-Puebla Fernández, Lidia
Ramírez Sebastián, José Manuel
Salazar Corral, Juan José
García López, Manuela
Ramírez Sebastián, Ana Isabel
author Fernández Albarral, José
author_facet Fernández Albarral, José
García Martín, Elena Salobrar
Matamoros Felipe, José Antonio
Fernández Mendivil, Cristina
Sastre, Eric, del
Chen, Leijing
Hoz Montañana, María Rosa De
López Cuenca, Inés
Sánchez-Puebla Fernández, Lidia
Ramírez Sebastián, José Manuel
Salazar Corral, Juan José
García López, Manuela
Ramírez Sebastián, Ana Isabel
author_role author
author2 García Martín, Elena Salobrar
Matamoros Felipe, José Antonio
Fernández Mendivil, Cristina
Sastre, Eric, del
Chen, Leijing
Hoz Montañana, María Rosa De
López Cuenca, Inés
Sánchez-Puebla Fernández, Lidia
Ramírez Sebastián, José Manuel
Salazar Corral, Juan José
García López, Manuela
Ramírez Sebastián, Ana Isabel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 617.735
611.8.018.24
Tauopathies
Heme oxygenase 1 (HO-1)
Retina
Microglia
Macroglia
Neuroinflammation
Neurodegenerative diseases
Oftalmología
Anatomía ocular
Medicina
Neurociencias (Medicina)
3201.09 Oftalmología
32 Ciencias Médicas
2490 Neurociencias
topic 617.735
611.8.018.24
Tauopathies
Heme oxygenase 1 (HO-1)
Retina
Microglia
Macroglia
Neuroinflammation
Neurodegenerative diseases
Oftalmología
Anatomía ocular
Medicina
Neurociencias (Medicina)
3201.09 Oftalmología
32 Ciencias Médicas
2490 Neurociencias
description Tauopathies such as Alzheimer’s disease are characterized by the accumulation of neurotoxic aggregates of tau protein. With aging and, especially, in Alzheimer’s patients, the inducible enzyme heme oxygenase 1 (HO-1) progressively increases in microglia, causing iron accumulation, neuroinflammation, and neurodegeneration. The retina is an organ that can be readily accessed and can reflect changes that occur in the brain. In this context, we evaluated how the lack of microglial HO-1, using mice that do not express HO-1 in microglia (HMO-KO), impacts retinal macro and microgliosis of aged subjects (18 months old mice) subjected to tauopathy by intrahippocampal delivery of AAV-hTauP301L (TAU). Our results show that although tauopathy, measured as anti-TAUY9 and anti-AT8 positive immunostaining, was not observed in the retina of WT-TAU or HMO-KO+TAU mice, a morphometric study of retinal microglia and macroglia showed significant retinal changes in the TAU group compared to the WT group, such as: (i) increased number of activated microglia, (ii) retraction of microglial processes, (iii) increased number of CD68+ microglia, and (iv) increased retinal area occupied by GFAP (AROA) and C3 (AROC3). This retinal inflammatory profile was reduced in HMO-KO+TAU mice. Conclusion: Reduction of microglial HO-1 could be beneficial to prevent tauopathy-induced neuroinflammation.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-10-30
2022
2022-10-30
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/72797
url https://hdl.handle.net/20.500.14352/72797
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 4.0 International
https://creativecommons.org/licenses/by/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 4.0 International
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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