Phenotypically aberrant astrocytes that promote motoneuron damage in a model of inherited amyotrophic lateral sclerosis

Autores
Diaz Amarilla, Pablo; Olivera Bravo, Silvia; Trias, Emiliano; Cragnolini, Andrea Beatriz; Martinez Palma, Laura; Cassina, Patricia; Beckman, Joseph; Barbeito, Luis
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Motoneuron loss and reactive astrocytosis are pathological hallmarks of amyotrophic lateral sclerosis (ALS), a paralytic neurodegenerative disease that can be triggered by mutations in Cu-Zn superoxide dismutase (SOD1). Dysfunctional astrocytes contribute to ALS pathogenesis, inducing motoneuron damage and accelerating disease progression. However, it is unknown whether ALS progression is associated with the appearance of a specific astrocytic phenotype with neurotoxic potential. Here, we report the isolation of astrocytes with aberrant phenotype (referred as “AbA cells”) from primary spinal cord cultures of symptomatic rats expressing the SOD1G93A mutation. Isolation was based on AbA cells’ marked proliferative capacity and lack of replicative senescence, which allowed oligoclonal cell expansion for 1 y. AbA cells displayed astrocytic markers including glial fibrillary acidic protein, S100β protein, glutamine synthase, and connexin 43 but lacked glutamate transporter 1 and the glial progenitor marker NG2 glycoprotein. Notably, AbA cells secreted soluble factors that induced motoneuron death with a 10-fold higher potency than neonatal SOD1G93A astrocytes. AbA-like aberrant astrocytes expressing S100β and connexin 43 but lacking NG2 were identified in nearby motoneurons, and their number increased sharply after disease onset. Thus, AbA cells appear to be an as-yet unknown astrocyte population arising during ALS progression with unprecedented proliferative and neurotoxic capacity and may be potential cellular targets for slowing ALS progression.
Fil: Diaz Amarilla, Pablo. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
Fil: Olivera Bravo, Silvia. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
Fil: Trias, Emiliano. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
Fil: Cragnolini, Andrea Beatriz. Instituto Pasteur de Montevideo. Laboratorio de Neurodegeneracion; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina
Fil: Martinez Palma, Laura. Universidad de la República; Uruguay. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
Fil: Cassina, Patricia. Universidad de la República; Uruguay
Fil: Beckman, Joseph. State University of Oregon; Estados Unidos. Environmental Health Sciences Center; Estados Unidos
Fil: Barbeito, Luis. Instituto Pasteur de Montevideo. Laboratorio de Neurodegeneracion; Uruguay. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
Materia
Astrocyte
Als
Spinal Cord
Motorneuron
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/43054
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Phenotypically aberrant astrocytes that promote motoneuron damage in a model of inherited amyotrophic lateral sclerosisDiaz Amarilla, PabloOlivera Bravo, SilviaTrias, EmilianoCragnolini, Andrea BeatrizMartinez Palma, LauraCassina, PatriciaBeckman, JosephBarbeito, LuisAstrocyteAlsSpinal CordMotorneuronhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Motoneuron loss and reactive astrocytosis are pathological hallmarks of amyotrophic lateral sclerosis (ALS), a paralytic neurodegenerative disease that can be triggered by mutations in Cu-Zn superoxide dismutase (SOD1). Dysfunctional astrocytes contribute to ALS pathogenesis, inducing motoneuron damage and accelerating disease progression. However, it is unknown whether ALS progression is associated with the appearance of a specific astrocytic phenotype with neurotoxic potential. Here, we report the isolation of astrocytes with aberrant phenotype (referred as “AbA cells”) from primary spinal cord cultures of symptomatic rats expressing the SOD1G93A mutation. Isolation was based on AbA cells’ marked proliferative capacity and lack of replicative senescence, which allowed oligoclonal cell expansion for 1 y. AbA cells displayed astrocytic markers including glial fibrillary acidic protein, S100β protein, glutamine synthase, and connexin 43 but lacked glutamate transporter 1 and the glial progenitor marker NG2 glycoprotein. Notably, AbA cells secreted soluble factors that induced motoneuron death with a 10-fold higher potency than neonatal SOD1G93A astrocytes. AbA-like aberrant astrocytes expressing S100β and connexin 43 but lacking NG2 were identified in nearby motoneurons, and their number increased sharply after disease onset. Thus, AbA cells appear to be an as-yet unknown astrocyte population arising during ALS progression with unprecedented proliferative and neurotoxic capacity and may be potential cellular targets for slowing ALS progression.Fil: Diaz Amarilla, Pablo. Instituto de Investigaciones Biológicas "Clemente Estable"; UruguayFil: Olivera Bravo, Silvia. Instituto de Investigaciones Biológicas "Clemente Estable"; UruguayFil: Trias, Emiliano. Instituto de Investigaciones Biológicas "Clemente Estable"; UruguayFil: Cragnolini, Andrea Beatriz. Instituto Pasteur de Montevideo. Laboratorio de Neurodegeneracion; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Martinez Palma, Laura. Universidad de la República; Uruguay. Instituto de Investigaciones Biológicas "Clemente Estable"; UruguayFil: Cassina, Patricia. Universidad de la República; UruguayFil: Beckman, Joseph. State University of Oregon; Estados Unidos. Environmental Health Sciences Center; Estados UnidosFil: Barbeito, Luis. Instituto Pasteur de Montevideo. Laboratorio de Neurodegeneracion; Uruguay. Instituto de Investigaciones Biológicas "Clemente Estable"; UruguayNational Academy of Sciences2011-11-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/43054Diaz Amarilla, Pablo; Olivera Bravo, Silvia; Trias, Emiliano; Cragnolini, Andrea Beatriz; Martinez Palma, Laura; et al.; Phenotypically aberrant astrocytes that promote motoneuron damage in a model of inherited amyotrophic lateral sclerosis; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 108; 44; 1-11-2011; 18126-181310027-84241091-6490CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/content/108/44/18126.full?sid=82f02297-7245-4428-b6dc-b3e618b9d62ainfo:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1110689108info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:53:20Zoai:ri.conicet.gov.ar:11336/43054instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:53:20.641CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Phenotypically aberrant astrocytes that promote motoneuron damage in a model of inherited amyotrophic lateral sclerosis
title Phenotypically aberrant astrocytes that promote motoneuron damage in a model of inherited amyotrophic lateral sclerosis
spellingShingle Phenotypically aberrant astrocytes that promote motoneuron damage in a model of inherited amyotrophic lateral sclerosis
Diaz Amarilla, Pablo
Astrocyte
Als
Spinal Cord
Motorneuron
title_short Phenotypically aberrant astrocytes that promote motoneuron damage in a model of inherited amyotrophic lateral sclerosis
title_full Phenotypically aberrant astrocytes that promote motoneuron damage in a model of inherited amyotrophic lateral sclerosis
title_fullStr Phenotypically aberrant astrocytes that promote motoneuron damage in a model of inherited amyotrophic lateral sclerosis
title_full_unstemmed Phenotypically aberrant astrocytes that promote motoneuron damage in a model of inherited amyotrophic lateral sclerosis
title_sort Phenotypically aberrant astrocytes that promote motoneuron damage in a model of inherited amyotrophic lateral sclerosis
dc.creator.none.fl_str_mv Diaz Amarilla, Pablo
Olivera Bravo, Silvia
Trias, Emiliano
Cragnolini, Andrea Beatriz
Martinez Palma, Laura
Cassina, Patricia
Beckman, Joseph
Barbeito, Luis
author Diaz Amarilla, Pablo
author_facet Diaz Amarilla, Pablo
Olivera Bravo, Silvia
Trias, Emiliano
Cragnolini, Andrea Beatriz
Martinez Palma, Laura
Cassina, Patricia
Beckman, Joseph
Barbeito, Luis
author_role author
author2 Olivera Bravo, Silvia
Trias, Emiliano
Cragnolini, Andrea Beatriz
Martinez Palma, Laura
Cassina, Patricia
Beckman, Joseph
Barbeito, Luis
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Astrocyte
Als
Spinal Cord
Motorneuron
topic Astrocyte
Als
Spinal Cord
Motorneuron
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Motoneuron loss and reactive astrocytosis are pathological hallmarks of amyotrophic lateral sclerosis (ALS), a paralytic neurodegenerative disease that can be triggered by mutations in Cu-Zn superoxide dismutase (SOD1). Dysfunctional astrocytes contribute to ALS pathogenesis, inducing motoneuron damage and accelerating disease progression. However, it is unknown whether ALS progression is associated with the appearance of a specific astrocytic phenotype with neurotoxic potential. Here, we report the isolation of astrocytes with aberrant phenotype (referred as “AbA cells”) from primary spinal cord cultures of symptomatic rats expressing the SOD1G93A mutation. Isolation was based on AbA cells’ marked proliferative capacity and lack of replicative senescence, which allowed oligoclonal cell expansion for 1 y. AbA cells displayed astrocytic markers including glial fibrillary acidic protein, S100β protein, glutamine synthase, and connexin 43 but lacked glutamate transporter 1 and the glial progenitor marker NG2 glycoprotein. Notably, AbA cells secreted soluble factors that induced motoneuron death with a 10-fold higher potency than neonatal SOD1G93A astrocytes. AbA-like aberrant astrocytes expressing S100β and connexin 43 but lacking NG2 were identified in nearby motoneurons, and their number increased sharply after disease onset. Thus, AbA cells appear to be an as-yet unknown astrocyte population arising during ALS progression with unprecedented proliferative and neurotoxic capacity and may be potential cellular targets for slowing ALS progression.
Fil: Diaz Amarilla, Pablo. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
Fil: Olivera Bravo, Silvia. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
Fil: Trias, Emiliano. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
Fil: Cragnolini, Andrea Beatriz. Instituto Pasteur de Montevideo. Laboratorio de Neurodegeneracion; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina
Fil: Martinez Palma, Laura. Universidad de la República; Uruguay. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
Fil: Cassina, Patricia. Universidad de la República; Uruguay
Fil: Beckman, Joseph. State University of Oregon; Estados Unidos. Environmental Health Sciences Center; Estados Unidos
Fil: Barbeito, Luis. Instituto Pasteur de Montevideo. Laboratorio de Neurodegeneracion; Uruguay. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
description Motoneuron loss and reactive astrocytosis are pathological hallmarks of amyotrophic lateral sclerosis (ALS), a paralytic neurodegenerative disease that can be triggered by mutations in Cu-Zn superoxide dismutase (SOD1). Dysfunctional astrocytes contribute to ALS pathogenesis, inducing motoneuron damage and accelerating disease progression. However, it is unknown whether ALS progression is associated with the appearance of a specific astrocytic phenotype with neurotoxic potential. Here, we report the isolation of astrocytes with aberrant phenotype (referred as “AbA cells”) from primary spinal cord cultures of symptomatic rats expressing the SOD1G93A mutation. Isolation was based on AbA cells’ marked proliferative capacity and lack of replicative senescence, which allowed oligoclonal cell expansion for 1 y. AbA cells displayed astrocytic markers including glial fibrillary acidic protein, S100β protein, glutamine synthase, and connexin 43 but lacked glutamate transporter 1 and the glial progenitor marker NG2 glycoprotein. Notably, AbA cells secreted soluble factors that induced motoneuron death with a 10-fold higher potency than neonatal SOD1G93A astrocytes. AbA-like aberrant astrocytes expressing S100β and connexin 43 but lacking NG2 were identified in nearby motoneurons, and their number increased sharply after disease onset. Thus, AbA cells appear to be an as-yet unknown astrocyte population arising during ALS progression with unprecedented proliferative and neurotoxic capacity and may be potential cellular targets for slowing ALS progression.
publishDate 2011
dc.date.none.fl_str_mv 2011-11-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/43054
Diaz Amarilla, Pablo; Olivera Bravo, Silvia; Trias, Emiliano; Cragnolini, Andrea Beatriz; Martinez Palma, Laura; et al.; Phenotypically aberrant astrocytes that promote motoneuron damage in a model of inherited amyotrophic lateral sclerosis; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 108; 44; 1-11-2011; 18126-18131
0027-8424
1091-6490
CONICET Digital
CONICET
url http://hdl.handle.net/11336/43054
identifier_str_mv Diaz Amarilla, Pablo; Olivera Bravo, Silvia; Trias, Emiliano; Cragnolini, Andrea Beatriz; Martinez Palma, Laura; et al.; Phenotypically aberrant astrocytes that promote motoneuron damage in a model of inherited amyotrophic lateral sclerosis; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 108; 44; 1-11-2011; 18126-18131
0027-8424
1091-6490
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/content/108/44/18126.full?sid=82f02297-7245-4428-b6dc-b3e618b9d62a
info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1110689108
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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