Ikzf1 as a novel regulator of microglial homeostasis in inflammation and neurodegeneration

Ballasch, Iván; García-García, Esther; Vila, Cristina; Pérez González, Anna; Sancho Balsells, Anna; Fernández, Jéssica; Soto del Cerro, David; Puigdellívol Cañadell, Maria del Mar; Gasull Casanova, Xavier; Alberch i Vié, Jordi, 1959-; Rodríguez Allué, Manuel José; Canals i Coll, Josep M.; Giralt Torroella, Albert

Ikzf1 as a novel regulator of microglial homeostasis in inflammation and neurodegeneration

Using genetic tools, here we describe that Ikzf1 is specifically expressed in the adult microglia in brain regions such as cortex and hippocampus. By characterizing the Ikzf1 deficient mice, we observed that these mice displayed spatial learning deficits, impaired hippocampal CA3-CA1 long-term poten...

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Autores:	Ballasch, Iván, García-García, Esther, Vila, Cristina, Pérez González, Anna, Sancho Balsells, Anna, Fernández, Jéssica, Soto del Cerro, David, Puigdellívol Cañadell, Maria del Mar, Gasull Casanova, Xavier, Alberch i Vié, Jordi, 1959-, Rodríguez Allué, Manuel José, Canals i Coll, Josep M., Giralt Torroella, Albert
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2023
País:	España
Institución:	Universidad de Barcelona
Repositorio:	Dipòsit Digital de la UB
OAI Identifier:	oai:diposit.ub.edu:2445/207664
Acceso en línea:	https://hdl.handle.net/2445/207664
Access Level:	acceso abierto
Palabra clave:	Hipocamp (Cervell) Malalties neurodegeneratives Micròglia Memòria Aprenentatge Escorça cerebral Hippocampus (Brain) Neurodegenerative Diseases Microglia Memory Learning Cerebral cortex

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spelling	Ikzf1 as a novel regulator of microglial homeostasis in inflammation and neurodegenerationBallasch, IvánGarcía-García, EstherVila, CristinaPérez González, AnnaSancho Balsells, AnnaFernández, JéssicaSoto del Cerro, DavidPuigdellívol Cañadell, Maria del MarGasull Casanova, XavierAlberch i Vié, Jordi, 1959-Rodríguez Allué, Manuel JoséCanals i Coll, Josep M.Giralt Torroella, AlbertHipocamp (Cervell)Malalties neurodegenerativesMicrògliaMemòriaAprenentatgeEscorça cerebralHippocampus (Brain)Neurodegenerative DiseasesMicrogliaMemoryLearningCerebral cortexUsing genetic tools, here we describe that Ikzf1 is specifically expressed in the adult microglia in brain regions such as cortex and hippocampus. By characterizing the Ikzf1 deficient mice, we observed that these mice displayed spatial learning deficits, impaired hippocampal CA3-CA1 long-term potentiation, and decreased spine density in pyramidal neurons of the CA1, which correlates with an increased expression of synaptic markers within microglia. Additionally, these Ikzf1 deficient microglia exhibited a severe abnormal morphology in the hippocampus, which is accompanied by astrogliosis, an aberrant composition of the inflammasome, and an altered expression of disease-associated microglia molecules. Interestingly, the lack of Ikzf1 induced changes on histone 3 acetylation and methylation levels in the hippocampus. Since the lack of Ikzf1 in mice appears to induce the internalization of synaptic markers within microglia, and severe gliosis we then analyzed hippocampal Ikzf1 levels in several models of neurological disorders. Ikzf1 levels were increased in the hippocampus of these neurological models, as well as in postmortem hippocampal samples from Alzheimer’s disease patients. Finally, over-expressing Ikzf1 in cultured microglia made these cells hyporeactive upon treatment with lipopolysaccharide, and less phagocytic compared to control microglia. Altogether, these results suggest that altered Ikzf1 levels in the adult hippocampus are sufficient to induce synaptic plasticity and memory deficits via altering microglial state and function.Elsevier2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/207664Articles publicats en revistes (Biomedicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1016/j.bbi.2023.01.016Brain, Behavior, and Immunity, 2023, vol. 109, p. 144-161https://doi.org/10.1016/j.bbi.2023.01.016cc-by-nc (c) Ballasch, Ivan et al., 2023http://creativecommons.org/licenses/by-nc/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2076642026-05-27T06:46:51Z
dc.title.none.fl_str_mv	Ikzf1 as a novel regulator of microglial homeostasis in inflammation and neurodegeneration
title	Ikzf1 as a novel regulator of microglial homeostasis in inflammation and neurodegeneration
spellingShingle	Ikzf1 as a novel regulator of microglial homeostasis in inflammation and neurodegeneration Ballasch, Iván Hipocamp (Cervell) Malalties neurodegeneratives Micròglia Memòria Aprenentatge Escorça cerebral Hippocampus (Brain) Neurodegenerative Diseases Microglia Memory Learning Cerebral cortex
title_short	Ikzf1 as a novel regulator of microglial homeostasis in inflammation and neurodegeneration
title_full	Ikzf1 as a novel regulator of microglial homeostasis in inflammation and neurodegeneration
title_fullStr	Ikzf1 as a novel regulator of microglial homeostasis in inflammation and neurodegeneration
title_full_unstemmed	Ikzf1 as a novel regulator of microglial homeostasis in inflammation and neurodegeneration
title_sort	Ikzf1 as a novel regulator of microglial homeostasis in inflammation and neurodegeneration
dc.creator.none.fl_str_mv	Ballasch, Iván García-García, Esther Vila, Cristina Pérez González, Anna Sancho Balsells, Anna Fernández, Jéssica Soto del Cerro, David Puigdellívol Cañadell, Maria del Mar Gasull Casanova, Xavier Alberch i Vié, Jordi, 1959- Rodríguez Allué, Manuel José Canals i Coll, Josep M. Giralt Torroella, Albert
author	Ballasch, Iván
author_facet	Ballasch, Iván García-García, Esther Vila, Cristina Pérez González, Anna Sancho Balsells, Anna Fernández, Jéssica Soto del Cerro, David Puigdellívol Cañadell, Maria del Mar Gasull Casanova, Xavier Alberch i Vié, Jordi, 1959- Rodríguez Allué, Manuel José Canals i Coll, Josep M. Giralt Torroella, Albert
author_role	author
author2	García-García, Esther Vila, Cristina Pérez González, Anna Sancho Balsells, Anna Fernández, Jéssica Soto del Cerro, David Puigdellívol Cañadell, Maria del Mar Gasull Casanova, Xavier Alberch i Vié, Jordi, 1959- Rodríguez Allué, Manuel José Canals i Coll, Josep M. Giralt Torroella, Albert
author2_role	author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Hipocamp (Cervell) Malalties neurodegeneratives Micròglia Memòria Aprenentatge Escorça cerebral Hippocampus (Brain) Neurodegenerative Diseases Microglia Memory Learning Cerebral cortex
topic	Hipocamp (Cervell) Malalties neurodegeneratives Micròglia Memòria Aprenentatge Escorça cerebral Hippocampus (Brain) Neurodegenerative Diseases Microglia Memory Learning Cerebral cortex
description	Using genetic tools, here we describe that Ikzf1 is specifically expressed in the adult microglia in brain regions such as cortex and hippocampus. By characterizing the Ikzf1 deficient mice, we observed that these mice displayed spatial learning deficits, impaired hippocampal CA3-CA1 long-term potentiation, and decreased spine density in pyramidal neurons of the CA1, which correlates with an increased expression of synaptic markers within microglia. Additionally, these Ikzf1 deficient microglia exhibited a severe abnormal morphology in the hippocampus, which is accompanied by astrogliosis, an aberrant composition of the inflammasome, and an altered expression of disease-associated microglia molecules. Interestingly, the lack of Ikzf1 induced changes on histone 3 acetylation and methylation levels in the hippocampus. Since the lack of Ikzf1 in mice appears to induce the internalization of synaptic markers within microglia, and severe gliosis we then analyzed hippocampal Ikzf1 levels in several models of neurological disorders. Ikzf1 levels were increased in the hippocampus of these neurological models, as well as in postmortem hippocampal samples from Alzheimer’s disease patients. Finally, over-expressing Ikzf1 in cultured microglia made these cells hyporeactive upon treatment with lipopolysaccharide, and less phagocytic compared to control microglia. Altogether, these results suggest that altered Ikzf1 levels in the adult hippocampus are sufficient to induce synaptic plasticity and memory deficits via altering microglial state and function.
publishDate	2023
dc.date.none.fl_str_mv	2023
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/2445/207664
url	https://hdl.handle.net/2445/207664
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Reproducció del document publicat a: https://doi.org/10.1016/j.bbi.2023.01.016 Brain, Behavior, and Immunity, 2023, vol. 109, p. 144-161 https://doi.org/10.1016/j.bbi.2023.01.016
dc.rights.none.fl_str_mv	cc-by-nc (c) Ballasch, Ivan et al., 2023 http://creativecommons.org/licenses/by-nc/3.0/es/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	cc-by-nc (c) Ballasch, Ivan et al., 2023 http://creativecommons.org/licenses/by-nc/3.0/es/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	Elsevier
publisher.none.fl_str_mv	Elsevier
dc.source.none.fl_str_mv	Articles publicats en revistes (Biomedicina) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona
instname_str	Universidad de Barcelona
reponame_str	Dipòsit Digital de la UB
collection	Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15,300719

Ikzf1 as a novel regulator of microglial homeostasis in inflammation and neurodegeneration

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