Clostridium perfringens epsilon toxin induces permanent neuronal degeneration and behavioral changes

Autores
Morris, Winston Eduardo; Goldstein, Jorge; Redondo, Leandro Martí­n; Cangelosi, Adriana; Geoghegan, Patricia; Brocco, Marcela Adriana; Loidl, Fabián C.; Fernandez Miyakawa, Mariano Enrique
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión aceptada
Descripción
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.
Inst. de Patobiología
Fil: Morris, Winston Eduardo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina
Fil: Goldstein, Jorge. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Redondo, Leandro Martí­n. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina
Fil: Cangelosi, Adriana. Centro Nacional de Control de Calidad de Biológicos; Argentina
Fil: Geoghegan, Patricia. Centro Nacional de Control de Calidad de Biológicos; Argentina
Fil: Brocco, Marcela Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); Argentina
Fil: Loidl, Fabián C. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Fernandez Miyakawa, Mariano Enrique. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fuente
Toxicon 130 :19-28. (May 2017)
Materia
Enfermedades de los Animales
Clostridium Perfringens
Toxinas
Enterotoxemia
Trastornos del Sistema Nervioso
Animal Diseases
Toxins
Enterotoxaemia
Nervous System Diseases
Nivel de accesibilidad
acceso restringido
Condiciones de uso
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/1345
Acceder
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oai_identifier_str oai:localhost:20.500.12123/1345
network_acronym_str INTADig
repository_id_str l
network_name_str INTA Digital (INTA)
spelling Clostridium perfringens epsilon toxin induces permanent neuronal degeneration and behavioral changesMorris, Winston EduardoGoldstein, JorgeRedondo, Leandro Martí­nCangelosi, AdrianaGeoghegan, PatriciaBrocco, Marcela AdrianaLoidl, Fabián C.Fernandez Miyakawa, Mariano EnriqueEnfermedades de los AnimalesClostridium PerfringensToxinasEnterotoxemiaTrastornos del Sistema NerviosoAnimal DiseasesToxinsEnterotoxaemiaNervous System DiseasesClostridium 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.Inst. de PatobiologíaFil: Morris, Winston Eduardo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; ArgentinaFil: Goldstein, Jorge. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Redondo, Leandro Martí­n. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; ArgentinaFil: Cangelosi, Adriana. Centro Nacional de Control de Calidad de Biológicos; ArgentinaFil: Geoghegan, Patricia. Centro Nacional de Control de Calidad de Biológicos; ArgentinaFil: Brocco, Marcela Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); ArgentinaFil: Loidl, Fabián C. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fernandez Miyakawa, Mariano Enrique. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina2017-09-28T12:55:41Z2017-09-28T12:55:41Z2017-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/1345http://www.sciencedirect.com/science/article/pii/S004101011730065X0041-0101 (Print)1879-3150 (Online)https://doi.org/10.1016/j.toxicon.2017.02.019Toxicon 130 :19-28. (May 2017)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/restrictedAccess2025-09-04T09:47:04Zoai:localhost:20.500.12123/1345instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-09-04 09:47:05.391INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
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 Eduardo
Enfermedades de los Animales
Clostridium Perfringens
Toxinas
Enterotoxemia
Trastornos del Sistema Nervioso
Animal Diseases
Toxins
Enterotoxaemia
Nervous System Diseases
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 Eduardo
Goldstein, Jorge
Redondo, Leandro Martí­n
Cangelosi, Adriana
Geoghegan, Patricia
Brocco, Marcela Adriana
Loidl, Fabián C.
Fernandez Miyakawa, Mariano Enrique
author Morris, Winston Eduardo
author_facet Morris, Winston Eduardo
Goldstein, Jorge
Redondo, Leandro Martí­n
Cangelosi, Adriana
Geoghegan, Patricia
Brocco, Marcela Adriana
Loidl, Fabián C.
Fernandez Miyakawa, Mariano Enrique
author_role author
author2 Goldstein, Jorge
Redondo, Leandro Martí­n
Cangelosi, Adriana
Geoghegan, Patricia
Brocco, Marcela Adriana
Loidl, Fabián C.
Fernandez Miyakawa, Mariano Enrique
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Enfermedades de los Animales
Clostridium Perfringens
Toxinas
Enterotoxemia
Trastornos del Sistema Nervioso
Animal Diseases
Toxins
Enterotoxaemia
Nervous System Diseases
topic Enfermedades de los Animales
Clostridium Perfringens
Toxinas
Enterotoxemia
Trastornos del Sistema Nervioso
Animal Diseases
Toxins
Enterotoxaemia
Nervous System Diseases
dc.description.none.fl_txt_mv 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.
Inst. de Patobiología
Fil: Morris, Winston Eduardo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina
Fil: Goldstein, Jorge. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Redondo, Leandro Martí­n. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina
Fil: Cangelosi, Adriana. Centro Nacional de Control de Calidad de Biológicos; Argentina
Fil: Geoghegan, Patricia. Centro Nacional de Control de Calidad de Biológicos; Argentina
Fil: Brocco, Marcela Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); Argentina
Fil: Loidl, Fabián C. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Fernandez Miyakawa, Mariano Enrique. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description 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.
publishDate 2017
dc.date.none.fl_str_mv 2017-09-28T12:55:41Z
2017-09-28T12:55:41Z
2017-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12123/1345
http://www.sciencedirect.com/science/article/pii/S004101011730065X
0041-0101 (Print)
1879-3150 (Online)
https://doi.org/10.1016/j.toxicon.2017.02.019
url http://hdl.handle.net/20.500.12123/1345
http://www.sciencedirect.com/science/article/pii/S004101011730065X
https://doi.org/10.1016/j.toxicon.2017.02.019
identifier_str_mv 0041-0101 (Print)
1879-3150 (Online)
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/restrictedAccess
eu_rights_str_mv restrictedAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv Toxicon 130 :19-28. (May 2017)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
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