Inflammation in multiple sclerosis induces a specific reactive astrocyte state driving non-cell-autonomous neuronal damage

Matute Blanch, Clara; Brito, Verónica; Midaglia, Luciana; Villar, Luisa M.; García-Díaz Barriga, Gerardo; Guzmán de la Fuente, Alerie; Borràs, Eva; Fernández, Sara (Fernández García); Calvo Barreiro, Laura; Miguez, Andrés; Costa Frossard, Lucienne; Pinteac, Rucsanda; Sabidó Aguadé, Eduard; Alberch i Vié, Jordi, 1959-; Fitzgerald, Denise C.; Montalbán Gairín, Xavier; Comabella, Manuel

Inflammation in multiple sclerosis induces a specific reactive astrocyte state driving non-cell-autonomous neuronal damage

An in‐depth understanding of the neurodegenerative component of multiple sclerosis (MS) is crucial for the design of therapeutic approaches that may stop disease progression. Astrocytes have emerged as key contributors to the pathogenesis of MS. 1 However, the mechanisms underlying the regulation of...

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Autores:	Matute Blanch, Clara, Brito, Verónica, Midaglia, Luciana, Villar, Luisa M., García-Díaz Barriga, Gerardo, Guzmán de la Fuente, Alerie, Borràs, Eva, Fernández, Sara (Fernández García), Calvo Barreiro, Laura, Miguez, Andrés, Costa Frossard, Lucienne, Pinteac, Rucsanda, Sabidó Aguadé, Eduard, Alberch i Vié, Jordi, 1959-, Fitzgerald, Denise C., Montalbán Gairín, Xavier, Comabella, Manuel
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2022
País:	España
Institución:	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:	Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:	oai:recercat.cat:2445/199925
Acceso en línea:	https://hdl.handle.net/2445/199925
Access Level:	acceso abierto
Palabra clave:	Inflamació Esclerosi múltiple Astròcits Cèl·lules canceroses Malalties neurodegeneratives Inflammation Multiple sclerosis Astrocytes Cancer cells Neurodegenerative Diseases

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spelling	Inflammation in multiple sclerosis induces a specific reactive astrocyte state driving non-cell-autonomous neuronal damageMatute Blanch, ClaraBrito, VerónicaMidaglia, LucianaVillar, Luisa M.García-Díaz Barriga, GerardoGuzmán de la Fuente, AlerieBorràs, EvaFernández, Sara (Fernández García)Calvo Barreiro, LauraMiguez, AndrésCosta Frossard, LuciennePinteac, RucsandaSabidó Aguadé, EduardAlberch i Vié, Jordi, 1959-Fitzgerald, Denise C.Montalbán Gairín, XavierComabella, ManuelInflamacióEsclerosi múltipleAstròcitsCèl·lules cancerosesMalalties neurodegenerativesInflammationMultiple sclerosisAstrocytesCancer cellsNeurodegenerative DiseasesAn in‐depth understanding of the neurodegenerative component of multiple sclerosis (MS) is crucial for the design of therapeutic approaches that may stop disease progression. Astrocytes have emerged as key contributors to the pathogenesis of MS. 1 However, the mechanisms underlying the regulation of maladaptive astrocytic responses remain unknown. In this report, we show that a high inflammatory activity in MS patients at disease onset induces a specific reactive astrocyte state that triggers synaptopathy and contributes to neuronal damage in vitro and ex vivo suggesting potential mechanisms that may ultimately lead to neurodegeneration. To investigate whether astrocytes are essential contributors to neuronal damage in MS, we cultured purified astrocytes with cerebrospinal fluid (CSF) samples from MS patients with high inflammatory activity at disease onset (MS‐High, Table S1). Then, we examined the effect of astrocytic secretomes on neurons (Figure 1A). Astrocytes became reactive upon high inflammatory CSF exposure (Figure 1B) and induced morphological alterations typically observed in neurodegenerative disorders, such as a less complex dendritic tree due to decreased arborisation (Figure 1C, D). Moreover, these abnormalities were accompanied with synaptic plasticity impairment (Figure 1E, F). Considering that a high lesion load at disease onset has been associated with an increased risk of neurological disability development, 2 we assessed whether the non‐cell‐autonomous effect on neuronal plasticity could be influenced by the degree of inflammatory activity of MS patients (Figure 2A and Table S1). Interestingly, we observed a direct correlation between the degree of inflammatory exposure and the extent of both astrocyte‐mediated synaptopathy (Figure 2B, C) and dendrite arborisation impairment.John Wiley & Sons2023202320222023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion8 p.application/pdfhttps://hdl.handle.net/2445/199925Articles publicats en revistes (Biomedicina)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1002/ctm2.837Clinical and Translational Medicine, 2022, vol. 12, num. 5https://doi.org/10.1002/ctm2.837cc-by (c) Matute Blanch, Clara et al., 2022https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1999252026-05-29T05:05:01Z
dc.title.none.fl_str_mv	Inflammation in multiple sclerosis induces a specific reactive astrocyte state driving non-cell-autonomous neuronal damage
title	Inflammation in multiple sclerosis induces a specific reactive astrocyte state driving non-cell-autonomous neuronal damage
spellingShingle	Inflammation in multiple sclerosis induces a specific reactive astrocyte state driving non-cell-autonomous neuronal damage Matute Blanch, Clara Inflamació Esclerosi múltiple Astròcits Cèl·lules canceroses Malalties neurodegeneratives Inflammation Multiple sclerosis Astrocytes Cancer cells Neurodegenerative Diseases
title_short	Inflammation in multiple sclerosis induces a specific reactive astrocyte state driving non-cell-autonomous neuronal damage
title_full	Inflammation in multiple sclerosis induces a specific reactive astrocyte state driving non-cell-autonomous neuronal damage
title_fullStr	Inflammation in multiple sclerosis induces a specific reactive astrocyte state driving non-cell-autonomous neuronal damage
title_full_unstemmed	Inflammation in multiple sclerosis induces a specific reactive astrocyte state driving non-cell-autonomous neuronal damage
title_sort	Inflammation in multiple sclerosis induces a specific reactive astrocyte state driving non-cell-autonomous neuronal damage
dc.creator.none.fl_str_mv	Matute Blanch, Clara Brito, Verónica Midaglia, Luciana Villar, Luisa M. García-Díaz Barriga, Gerardo Guzmán de la Fuente, Alerie Borràs, Eva Fernández, Sara (Fernández García) Calvo Barreiro, Laura Miguez, Andrés Costa Frossard, Lucienne Pinteac, Rucsanda Sabidó Aguadé, Eduard Alberch i Vié, Jordi, 1959- Fitzgerald, Denise C. Montalbán Gairín, Xavier Comabella, Manuel
author	Matute Blanch, Clara
author_facet	Matute Blanch, Clara Brito, Verónica Midaglia, Luciana Villar, Luisa M. García-Díaz Barriga, Gerardo Guzmán de la Fuente, Alerie Borràs, Eva Fernández, Sara (Fernández García) Calvo Barreiro, Laura Miguez, Andrés Costa Frossard, Lucienne Pinteac, Rucsanda Sabidó Aguadé, Eduard Alberch i Vié, Jordi, 1959- Fitzgerald, Denise C. Montalbán Gairín, Xavier Comabella, Manuel
author_role	author
author2	Brito, Verónica Midaglia, Luciana Villar, Luisa M. García-Díaz Barriga, Gerardo Guzmán de la Fuente, Alerie Borràs, Eva Fernández, Sara (Fernández García) Calvo Barreiro, Laura Miguez, Andrés Costa Frossard, Lucienne Pinteac, Rucsanda Sabidó Aguadé, Eduard Alberch i Vié, Jordi, 1959- Fitzgerald, Denise C. Montalbán Gairín, Xavier Comabella, Manuel
author2_role	author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Inflamació Esclerosi múltiple Astròcits Cèl·lules canceroses Malalties neurodegeneratives Inflammation Multiple sclerosis Astrocytes Cancer cells Neurodegenerative Diseases
topic	Inflamació Esclerosi múltiple Astròcits Cèl·lules canceroses Malalties neurodegeneratives Inflammation Multiple sclerosis Astrocytes Cancer cells Neurodegenerative Diseases
description	An in‐depth understanding of the neurodegenerative component of multiple sclerosis (MS) is crucial for the design of therapeutic approaches that may stop disease progression. Astrocytes have emerged as key contributors to the pathogenesis of MS. 1 However, the mechanisms underlying the regulation of maladaptive astrocytic responses remain unknown. In this report, we show that a high inflammatory activity in MS patients at disease onset induces a specific reactive astrocyte state that triggers synaptopathy and contributes to neuronal damage in vitro and ex vivo suggesting potential mechanisms that may ultimately lead to neurodegeneration. To investigate whether astrocytes are essential contributors to neuronal damage in MS, we cultured purified astrocytes with cerebrospinal fluid (CSF) samples from MS patients with high inflammatory activity at disease onset (MS‐High, Table S1). Then, we examined the effect of astrocytic secretomes on neurons (Figure 1A). Astrocytes became reactive upon high inflammatory CSF exposure (Figure 1B) and induced morphological alterations typically observed in neurodegenerative disorders, such as a less complex dendritic tree due to decreased arborisation (Figure 1C, D). Moreover, these abnormalities were accompanied with synaptic plasticity impairment (Figure 1E, F). Considering that a high lesion load at disease onset has been associated with an increased risk of neurological disability development, 2 we assessed whether the non‐cell‐autonomous effect on neuronal plasticity could be influenced by the degree of inflammatory activity of MS patients (Figure 2A and Table S1). Interestingly, we observed a direct correlation between the degree of inflammatory exposure and the extent of both astrocyte‐mediated synaptopathy (Figure 2B, C) and dendrite arborisation impairment.
publishDate	2022
dc.date.none.fl_str_mv	2022 2023 2023 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/2445/199925
url	https://hdl.handle.net/2445/199925
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/10.1002/ctm2.837 Clinical and Translational Medicine, 2022, vol. 12, num. 5 https://doi.org/10.1002/ctm2.837
dc.rights.none.fl_str_mv	cc-by (c) Matute Blanch, Clara et al., 2022 https://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	cc-by (c) Matute Blanch, Clara et al., 2022 https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	8 p. application/pdf
dc.publisher.none.fl_str_mv	John Wiley & Sons
publisher.none.fl_str_mv	John Wiley & Sons
dc.source.none.fl_str_mv	Articles publicats en revistes (Biomedicina) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str	Recercat. Dipósit de la Recerca de Catalunya
collection	Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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Inflammation in multiple sclerosis induces a specific reactive astrocyte state driving non-cell-autonomous neuronal damage

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