A Translational Murine Model of Sub-Lethal Intoxication with Shiga Toxin 2 Reveals Novel Ultrastructural Findings in the Brain Striatum

Autores
Tironi Farinati, Alicia Carla Flavia; Geoghegan, Patricia A.; Cangelosi, Adriana; Pinto, Alipio; Loidl, Cesar Fabian; Goldstein, Jorge
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Infection by Shiga toxin-producing Escherichia coli causes hemorrhagic colitis, hemolytic uremic syndrome (HUS), acute renal failure, and also central nervous system complications in around 30% of the children affected. Besides, neurological deficits are one of the most unrepairable and untreatable outcomes of HUS. Study of the striatum is relevant because basal ganglia are one of the brain areas most commonly affected in patients that have suffered from HUS and since the deleterious effects of a sub-lethal dose of Shiga toxin have never been studied in the striatum, the purpose of this study was to attempt to simulate an infection by Shiga toxin-producing E. coli in a murine model. To this end, intravenous administration of a sub-lethal dose of Shiga toxin 2 (0.5 ηg per mouse) was used and the correlation between neurological manifestations and ultrastructural changes in striatal brain cells was studied in detail. Neurological manifestations included significant motor behavior abnormalities in spontaneous motor activity, gait, pelvic elevation and hind limb activity eight days after administration of the toxin. Transmission electron microscopy revealed that the toxin caused early perivascular edema two days after administration, as well as significant damage in astrocytes four days after administration and significant damage in neurons and oligodendrocytes eight days after administration. Interrupted synapses and mast cell extravasation were also found eight days after administration of the toxin. We thus conclude that the chronological order of events observed in the striatum could explain the neurological disorders found eight days after administration of the toxin.
Fil: Tironi Farinati, Alicia Carla Flavia. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Geoghegan, Patricia A.. Ministerio de Salud de la Nación. Administración Nacional de Laboratorios e Institutos de Salud; Argentina
Fil: Cangelosi, Adriana. Ministerio de Salud de la Nación. Administración Nacional de Laboratorios e Institutos de Salud; Argentina
Fil: Pinto, Alipio. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Fisiología. Laboratorio de Neurofisiopatología; Argentina
Fil: Loidl, Cesar Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencias.;
Fil: Goldstein, Jorge. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Fisiología. Laboratorio de Neurofisiopatología; Argentina
Materia
Shiga Toxin
Encephalopathy
Motor Abnormalities
Ultrastructural Changes
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:11336/1699
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/1699
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A Translational Murine Model of Sub-Lethal Intoxication with Shiga Toxin 2 Reveals Novel Ultrastructural Findings in the Brain StriatumTironi Farinati, Alicia Carla FlaviaGeoghegan, Patricia A.Cangelosi, AdrianaPinto, AlipioLoidl, Cesar FabianGoldstein, JorgeShiga ToxinEncephalopathyMotor AbnormalitiesUltrastructural Changeshttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Infection by Shiga toxin-producing Escherichia coli causes hemorrhagic colitis, hemolytic uremic syndrome (HUS), acute renal failure, and also central nervous system complications in around 30% of the children affected. Besides, neurological deficits are one of the most unrepairable and untreatable outcomes of HUS. Study of the striatum is relevant because basal ganglia are one of the brain areas most commonly affected in patients that have suffered from HUS and since the deleterious effects of a sub-lethal dose of Shiga toxin have never been studied in the striatum, the purpose of this study was to attempt to simulate an infection by Shiga toxin-producing E. coli in a murine model. To this end, intravenous administration of a sub-lethal dose of Shiga toxin 2 (0.5 ηg per mouse) was used and the correlation between neurological manifestations and ultrastructural changes in striatal brain cells was studied in detail. Neurological manifestations included significant motor behavior abnormalities in spontaneous motor activity, gait, pelvic elevation and hind limb activity eight days after administration of the toxin. Transmission electron microscopy revealed that the toxin caused early perivascular edema two days after administration, as well as significant damage in astrocytes four days after administration and significant damage in neurons and oligodendrocytes eight days after administration. Interrupted synapses and mast cell extravasation were also found eight days after administration of the toxin. We thus conclude that the chronological order of events observed in the striatum could explain the neurological disorders found eight days after administration of the toxin.Fil: Tironi Farinati, Alicia Carla Flavia. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Geoghegan, Patricia A.. Ministerio de Salud de la Nación. Administración Nacional de Laboratorios e Institutos de Salud; ArgentinaFil: Cangelosi, Adriana. Ministerio de Salud de la Nación. Administración Nacional de Laboratorios e Institutos de Salud; ArgentinaFil: Pinto, Alipio. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Fisiología. Laboratorio de Neurofisiopatología; ArgentinaFil: Loidl, Cesar Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencias.;Fil: Goldstein, Jorge. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Fisiología. Laboratorio de Neurofisiopatología; ArgentinaPublic Library Of Science2013-01-31info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/1699Tironi Farinati, Alicia Carla Flavia; Geoghegan, Patricia A.; Cangelosi, Adriana; Pinto, Alipio; Loidl, Cesar Fabian; et al.; A Translational Murine Model of Sub-Lethal Intoxication with Shiga Toxin 2 Reveals Novel Ultrastructural Findings in the Brain Striatum; Public Library Of Science; Plos One; 8; 1; 31-1-2013; 111932-6203enginfo:eu-repo/semantics/altIdentifier/doi/DOI:10.1371/journal.pone.0055812info:eu-repo/semantics/altIdentifier/url/http://www.plosone.org/article/fetchObject.action?uri=info:doi/10.1371/journal.pone.0055812&representation=PDFinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:56:20Zoai:ri.conicet.gov.ar:11336/1699instacron: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:34982025-10-22 11:56:20.335CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A Translational Murine Model of Sub-Lethal Intoxication with Shiga Toxin 2 Reveals Novel Ultrastructural Findings in the Brain Striatum
title A Translational Murine Model of Sub-Lethal Intoxication with Shiga Toxin 2 Reveals Novel Ultrastructural Findings in the Brain Striatum
spellingShingle A Translational Murine Model of Sub-Lethal Intoxication with Shiga Toxin 2 Reveals Novel Ultrastructural Findings in the Brain Striatum
Tironi Farinati, Alicia Carla Flavia
Shiga Toxin
Encephalopathy
Motor Abnormalities
Ultrastructural Changes
title_short A Translational Murine Model of Sub-Lethal Intoxication with Shiga Toxin 2 Reveals Novel Ultrastructural Findings in the Brain Striatum
title_full A Translational Murine Model of Sub-Lethal Intoxication with Shiga Toxin 2 Reveals Novel Ultrastructural Findings in the Brain Striatum
title_fullStr A Translational Murine Model of Sub-Lethal Intoxication with Shiga Toxin 2 Reveals Novel Ultrastructural Findings in the Brain Striatum
title_full_unstemmed A Translational Murine Model of Sub-Lethal Intoxication with Shiga Toxin 2 Reveals Novel Ultrastructural Findings in the Brain Striatum
title_sort A Translational Murine Model of Sub-Lethal Intoxication with Shiga Toxin 2 Reveals Novel Ultrastructural Findings in the Brain Striatum
dc.creator.none.fl_str_mv Tironi Farinati, Alicia Carla Flavia
Geoghegan, Patricia A.
Cangelosi, Adriana
Pinto, Alipio
Loidl, Cesar Fabian
Goldstein, Jorge
author Tironi Farinati, Alicia Carla Flavia
author_facet Tironi Farinati, Alicia Carla Flavia
Geoghegan, Patricia A.
Cangelosi, Adriana
Pinto, Alipio
Loidl, Cesar Fabian
Goldstein, Jorge
author_role author
author2 Geoghegan, Patricia A.
Cangelosi, Adriana
Pinto, Alipio
Loidl, Cesar Fabian
Goldstein, Jorge
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Shiga Toxin
Encephalopathy
Motor Abnormalities
Ultrastructural Changes
topic Shiga Toxin
Encephalopathy
Motor Abnormalities
Ultrastructural Changes
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Infection by Shiga toxin-producing Escherichia coli causes hemorrhagic colitis, hemolytic uremic syndrome (HUS), acute renal failure, and also central nervous system complications in around 30% of the children affected. Besides, neurological deficits are one of the most unrepairable and untreatable outcomes of HUS. Study of the striatum is relevant because basal ganglia are one of the brain areas most commonly affected in patients that have suffered from HUS and since the deleterious effects of a sub-lethal dose of Shiga toxin have never been studied in the striatum, the purpose of this study was to attempt to simulate an infection by Shiga toxin-producing E. coli in a murine model. To this end, intravenous administration of a sub-lethal dose of Shiga toxin 2 (0.5 ηg per mouse) was used and the correlation between neurological manifestations and ultrastructural changes in striatal brain cells was studied in detail. Neurological manifestations included significant motor behavior abnormalities in spontaneous motor activity, gait, pelvic elevation and hind limb activity eight days after administration of the toxin. Transmission electron microscopy revealed that the toxin caused early perivascular edema two days after administration, as well as significant damage in astrocytes four days after administration and significant damage in neurons and oligodendrocytes eight days after administration. Interrupted synapses and mast cell extravasation were also found eight days after administration of the toxin. We thus conclude that the chronological order of events observed in the striatum could explain the neurological disorders found eight days after administration of the toxin.
Fil: Tironi Farinati, Alicia Carla Flavia. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Geoghegan, Patricia A.. Ministerio de Salud de la Nación. Administración Nacional de Laboratorios e Institutos de Salud; Argentina
Fil: Cangelosi, Adriana. Ministerio de Salud de la Nación. Administración Nacional de Laboratorios e Institutos de Salud; Argentina
Fil: Pinto, Alipio. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Fisiología. Laboratorio de Neurofisiopatología; Argentina
Fil: Loidl, Cesar Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencias.;
Fil: Goldstein, Jorge. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Fisiología. Laboratorio de Neurofisiopatología; Argentina
description Infection by Shiga toxin-producing Escherichia coli causes hemorrhagic colitis, hemolytic uremic syndrome (HUS), acute renal failure, and also central nervous system complications in around 30% of the children affected. Besides, neurological deficits are one of the most unrepairable and untreatable outcomes of HUS. Study of the striatum is relevant because basal ganglia are one of the brain areas most commonly affected in patients that have suffered from HUS and since the deleterious effects of a sub-lethal dose of Shiga toxin have never been studied in the striatum, the purpose of this study was to attempt to simulate an infection by Shiga toxin-producing E. coli in a murine model. To this end, intravenous administration of a sub-lethal dose of Shiga toxin 2 (0.5 ηg per mouse) was used and the correlation between neurological manifestations and ultrastructural changes in striatal brain cells was studied in detail. Neurological manifestations included significant motor behavior abnormalities in spontaneous motor activity, gait, pelvic elevation and hind limb activity eight days after administration of the toxin. Transmission electron microscopy revealed that the toxin caused early perivascular edema two days after administration, as well as significant damage in astrocytes four days after administration and significant damage in neurons and oligodendrocytes eight days after administration. Interrupted synapses and mast cell extravasation were also found eight days after administration of the toxin. We thus conclude that the chronological order of events observed in the striatum could explain the neurological disorders found eight days after administration of the toxin.
publishDate 2013
dc.date.none.fl_str_mv 2013-01-31
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/11336/1699
Tironi Farinati, Alicia Carla Flavia; Geoghegan, Patricia A.; Cangelosi, Adriana; Pinto, Alipio; Loidl, Cesar Fabian; et al.; A Translational Murine Model of Sub-Lethal Intoxication with Shiga Toxin 2 Reveals Novel Ultrastructural Findings in the Brain Striatum; Public Library Of Science; Plos One; 8; 1; 31-1-2013; 11
1932-6203
url http://hdl.handle.net/11336/1699
identifier_str_mv Tironi Farinati, Alicia Carla Flavia; Geoghegan, Patricia A.; Cangelosi, Adriana; Pinto, Alipio; Loidl, Cesar Fabian; et al.; A Translational Murine Model of Sub-Lethal Intoxication with Shiga Toxin 2 Reveals Novel Ultrastructural Findings in the Brain Striatum; Public Library Of Science; Plos One; 8; 1; 31-1-2013; 11
1932-6203
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/DOI:10.1371/journal.pone.0055812
info:eu-repo/semantics/altIdentifier/url/http://www.plosone.org/article/fetchObject.action?uri=info:doi/10.1371/journal.pone.0055812&representation=PDF
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 Public Library Of Science
publisher.none.fl_str_mv Public Library Of Science
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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