Clostridium perfringens epsilon toxin induces permanent neuronal degeneration and behavioral changes

Autores
Morris, Winston E; Goldstein, Jorge; Redondo, Leandro M; Cangelosi, Adriana; Geoghegan, Patricia A.; Brocco, Marcela; Loidl, Fabián C; Fernández-Miyakawa, Mariano E
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Fil: Morris, Winston E. Instituto Nacional de Tecnología Agropecuaria. Centro Nacional de Investigaciones Agropecuarias. Instituto de Patobiología; Argentina.
Fil: Goldstein, Jorge. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Fisiología; Argentina.
Fil: Redondo, Leandro M. Instituto Nacional de Tecnología Agropecuaria. Centro Nacional de Investigaciones Agropecuarias. Instituto de Patobiología; Argentina.
Fil: Cangelosi, Adriana. ANLIS Dr.C.G.Malbrán. Centro Nacional de Control de Calidad de Biológicos; Argentina.
Fil: Geoghegan, Patricia A. ANLIS Dr.C.G.Malbrán. Centro Nacional de Control de Calidad de Biológicos; Argentina.
Fil: Brocco, Marcela. Universidad Nacional de San Martin. Instituto de Investigaciones Biotecnológicas; Argentina.
Fil: Loidl, Fabián C. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencias Prof. E. De Robertis; Argentina.
Fil: Fernández-Miyakawa, Mariano E. Instituto Nacional de Tecnología Agropecuaria. Centro Nacional de Investigaciones Agropecuarias. Instituto de Patobiología; Argentina.
Clostridium perfringens epsilon toxin (ETX), the most potent toxin produced by this bacteria, plays a key role in the pathogenesis of enterotoxaemia in ruminants, causing brain edema and encephalomalacia. Studies of animals suffering from ETX intoxication describe severe neurological disorders that are thought to be the result of vasogenic brain edemas and indirect neuronal toxicity, killing oligodendrocytes but not astrocytes, microglia, or neurons in vitro. In this study, by means of intravenous and intracerebroventricular delivery of sub-lethal concentrations of ETX, the histological and ultrastructural changes of the brain were studied in rats and mice. Histological analysis showed degenerative changes in neurons from the cortex, hippocampus, striatum and hypothalamus. Ultrastructurally, necrotic neurons and apoptotic cells were observed in these same areas, among axons with accumulation of neurofilaments and demyelination as well as synaptic stripping. Lesions observed in the brain after sub-lethal exposure to ETX, result in permanent behavioral changes in animals surviving ETX exposure, as observed individually in several animals and assessed in the Inclined Plane Test and the Wire Hang Test. Pharmacological studies showed that dexamethasone and reserpine but not ketamine or riluzole were able to reduce the brain lesions and the lethality of ETX. Cytotoxicity was not observed upon neuronal primary cultures in vitro. Therefore, we hypothesize that ETX can affect the brain of animals independently of death, producing changes on neurons or glia as the result of complex interactions, independently of ETX-BBB interactions.
Materia
Distrofias Neuroaxonales
Conducta
Cerebro
Clostridium perfringens
Enterotoxemia
Nivel de accesibilidad
acceso abierto
Condiciones de uso
none
Repositorio
Sistema de Gestión del Conocimiento ANLIS MALBRÁN
Institución
Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
OAI Identificador
oai:sgc.anlis.gob.ar:Publications/123456789/1643

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network_name_str Sistema de Gestión del Conocimiento ANLIS MALBRÁN
spelling Clostridium perfringens epsilon toxin induces permanent neuronal degeneration and behavioral changesMorris, Winston EGoldstein, JorgeRedondo, Leandro MCangelosi, AdrianaGeoghegan, Patricia A.Brocco, MarcelaLoidl, Fabián CFernández-Miyakawa, Mariano EDistrofias NeuroaxonalesConductaCerebroClostridium perfringensEnterotoxemiaFil: Morris, Winston E. Instituto Nacional de Tecnología Agropecuaria. Centro Nacional de Investigaciones Agropecuarias. Instituto de Patobiología; Argentina.Fil: Goldstein, Jorge. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Fisiología; Argentina.Fil: Redondo, Leandro M. Instituto Nacional de Tecnología Agropecuaria. Centro Nacional de Investigaciones Agropecuarias. Instituto de Patobiología; Argentina.Fil: Cangelosi, Adriana. ANLIS Dr.C.G.Malbrán. Centro Nacional de Control de Calidad de Biológicos; Argentina.Fil: Geoghegan, Patricia A. ANLIS Dr.C.G.Malbrán. Centro Nacional de Control de Calidad de Biológicos; Argentina.Fil: Brocco, Marcela. Universidad Nacional de San Martin. Instituto de Investigaciones Biotecnológicas; Argentina.Fil: Loidl, Fabián C. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencias Prof. E. De Robertis; Argentina.Fil: Fernández-Miyakawa, Mariano E. Instituto Nacional de Tecnología Agropecuaria. Centro Nacional de Investigaciones Agropecuarias. Instituto de Patobiología; Argentina.Clostridium perfringens epsilon toxin (ETX), the most potent toxin produced by this bacteria, plays a key role in the pathogenesis of enterotoxaemia in ruminants, causing brain edema and encephalomalacia. Studies of animals suffering from ETX intoxication describe severe neurological disorders that are thought to be the result of vasogenic brain edemas and indirect neuronal toxicity, killing oligodendrocytes but not astrocytes, microglia, or neurons in vitro. In this study, by means of intravenous and intracerebroventricular delivery of sub-lethal concentrations of ETX, the histological and ultrastructural changes of the brain were studied in rats and mice. Histological analysis showed degenerative changes in neurons from the cortex, hippocampus, striatum and hypothalamus. Ultrastructurally, necrotic neurons and apoptotic cells were observed in these same areas, among axons with accumulation of neurofilaments and demyelination as well as synaptic stripping. Lesions observed in the brain after sub-lethal exposure to ETX, result in permanent behavioral changes in animals surviving ETX exposure, as observed individually in several animals and assessed in the Inclined Plane Test and the Wire Hang Test. Pharmacological studies showed that dexamethasone and reserpine but not ketamine or riluzole were able to reduce the brain lesions and the lethality of ETX. Cytotoxicity was not observed upon neuronal primary cultures in vitro. Therefore, we hypothesize that ETX can affect the brain of animals independently of death, producing changes on neurons or glia as the result of complex interactions, independently of ETX-BBB interactions.2017-05info:ar-repo/semantics/articuloinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://sgc.anlis.gob.ar/handle/123456789/164310.1016/j.toxicon.2017.02.019Toxicon : official journal of the International Society on Toxinologynoneinfo:eu-repo/semantics/openAccessengreponame:Sistema de Gestión del Conocimiento ANLIS MALBRÁNinstname:Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"instacron:ANLIS2025-09-04T11:17:12Zoai:sgc.anlis.gob.ar:Publications/123456789/1643Institucionalhttp://sgc.anlis.gob.ar/Organismo científico-tecnológicoNo correspondehttp://sgc.anlis.gob.ar/oai/biblioteca@anlis.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:a2025-09-04 11:17:12.572Sistema de Gestión del Conocimiento ANLIS MALBRÁN - Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"false
dc.title.none.fl_str_mv Clostridium perfringens epsilon toxin induces permanent neuronal degeneration and behavioral changes
title Clostridium perfringens epsilon toxin induces permanent neuronal degeneration and behavioral changes
spellingShingle Clostridium perfringens epsilon toxin induces permanent neuronal degeneration and behavioral changes
Morris, Winston E
Distrofias Neuroaxonales
Conducta
Cerebro
Clostridium perfringens
Enterotoxemia
title_short Clostridium perfringens epsilon toxin induces permanent neuronal degeneration and behavioral changes
title_full Clostridium perfringens epsilon toxin induces permanent neuronal degeneration and behavioral changes
title_fullStr Clostridium perfringens epsilon toxin induces permanent neuronal degeneration and behavioral changes
title_full_unstemmed Clostridium perfringens epsilon toxin induces permanent neuronal degeneration and behavioral changes
title_sort Clostridium perfringens epsilon toxin induces permanent neuronal degeneration and behavioral changes
dc.creator.none.fl_str_mv Morris, Winston E
Goldstein, Jorge
Redondo, Leandro M
Cangelosi, Adriana
Geoghegan, Patricia A.
Brocco, Marcela
Loidl, Fabián C
Fernández-Miyakawa, Mariano E
author Morris, Winston E
author_facet Morris, Winston E
Goldstein, Jorge
Redondo, Leandro M
Cangelosi, Adriana
Geoghegan, Patricia A.
Brocco, Marcela
Loidl, Fabián C
Fernández-Miyakawa, Mariano E
author_role author
author2 Goldstein, Jorge
Redondo, Leandro M
Cangelosi, Adriana
Geoghegan, Patricia A.
Brocco, Marcela
Loidl, Fabián C
Fernández-Miyakawa, Mariano E
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Distrofias Neuroaxonales
Conducta
Cerebro
Clostridium perfringens
Enterotoxemia
topic Distrofias Neuroaxonales
Conducta
Cerebro
Clostridium perfringens
Enterotoxemia
dc.description.none.fl_txt_mv Fil: Morris, Winston E. Instituto Nacional de Tecnología Agropecuaria. Centro Nacional de Investigaciones Agropecuarias. Instituto de Patobiología; Argentina.
Fil: Goldstein, Jorge. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Fisiología; Argentina.
Fil: Redondo, Leandro M. Instituto Nacional de Tecnología Agropecuaria. Centro Nacional de Investigaciones Agropecuarias. Instituto de Patobiología; Argentina.
Fil: Cangelosi, Adriana. ANLIS Dr.C.G.Malbrán. Centro Nacional de Control de Calidad de Biológicos; Argentina.
Fil: Geoghegan, Patricia A. ANLIS Dr.C.G.Malbrán. Centro Nacional de Control de Calidad de Biológicos; Argentina.
Fil: Brocco, Marcela. Universidad Nacional de San Martin. Instituto de Investigaciones Biotecnológicas; Argentina.
Fil: Loidl, Fabián C. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencias Prof. E. De Robertis; Argentina.
Fil: Fernández-Miyakawa, Mariano E. Instituto Nacional de Tecnología Agropecuaria. Centro Nacional de Investigaciones Agropecuarias. Instituto de Patobiología; Argentina.
Clostridium perfringens epsilon toxin (ETX), the most potent toxin produced by this bacteria, plays a key role in the pathogenesis of enterotoxaemia in ruminants, causing brain edema and encephalomalacia. Studies of animals suffering from ETX intoxication describe severe neurological disorders that are thought to be the result of vasogenic brain edemas and indirect neuronal toxicity, killing oligodendrocytes but not astrocytes, microglia, or neurons in vitro. In this study, by means of intravenous and intracerebroventricular delivery of sub-lethal concentrations of ETX, the histological and ultrastructural changes of the brain were studied in rats and mice. Histological analysis showed degenerative changes in neurons from the cortex, hippocampus, striatum and hypothalamus. Ultrastructurally, necrotic neurons and apoptotic cells were observed in these same areas, among axons with accumulation of neurofilaments and demyelination as well as synaptic stripping. Lesions observed in the brain after sub-lethal exposure to ETX, result in permanent behavioral changes in animals surviving ETX exposure, as observed individually in several animals and assessed in the Inclined Plane Test and the Wire Hang Test. Pharmacological studies showed that dexamethasone and reserpine but not ketamine or riluzole were able to reduce the brain lesions and the lethality of ETX. Cytotoxicity was not observed upon neuronal primary cultures in vitro. Therefore, we hypothesize that ETX can affect the brain of animals independently of death, producing changes on neurons or glia as the result of complex interactions, independently of ETX-BBB interactions.
description Fil: Morris, Winston E. Instituto Nacional de Tecnología Agropecuaria. Centro Nacional de Investigaciones Agropecuarias. Instituto de Patobiología; Argentina.
publishDate 2017
dc.date.none.fl_str_mv 2017-05
dc.type.none.fl_str_mv info:ar-repo/semantics/articulo
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sgc.anlis.gob.ar/handle/123456789/1643
10.1016/j.toxicon.2017.02.019
url http://sgc.anlis.gob.ar/handle/123456789/1643
identifier_str_mv 10.1016/j.toxicon.2017.02.019
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Toxicon : official journal of the International Society on Toxinology
dc.rights.none.fl_str_mv none
info:eu-repo/semantics/openAccess
rights_invalid_str_mv none
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Sistema de Gestión del Conocimiento ANLIS MALBRÁN
instname:Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
instacron:ANLIS
reponame_str Sistema de Gestión del Conocimiento ANLIS MALBRÁN
collection Sistema de Gestión del Conocimiento ANLIS MALBRÁN
instname_str Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
instacron_str ANLIS
institution ANLIS
repository.name.fl_str_mv Sistema de Gestión del Conocimiento ANLIS MALBRÁN - Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
repository.mail.fl_str_mv biblioteca@anlis.gov.ar
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