Clostridium perfringens epsilon toxin induces permanent neuronal degeneration and behavioral changes
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...
| Autores principales: | , , , , , , , |
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| Formato: | Artículo |
| Lenguaje: | Inglés |
| Publicado: |
2017
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| Acceso en línea: | 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 |
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| author | Morris, Winston Eduardo Goldstein, Jorge Redondo, Leandro Martín Cangelosi, Adriana Geoghegan, Patricia Brocco, Marcela Adriana Loidl, Fabián C. Fernandez Miyakawa, Mariano Enrique |
| author_browse | Brocco, Marcela Adriana Cangelosi, Adriana Fernandez Miyakawa, Mariano Enrique Geoghegan, Patricia Goldstein, Jorge Loidl, Fabián C. Morris, Winston Eduardo Redondo, Leandro Martín |
| 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_sort | Morris, Winston Eduardo |
| collection | INTA Digital |
| 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. |
| format | Artículo |
| id | INTA1345 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2017 |
| publishDateRange | 2017 |
| publishDateSort | 2017 |
| record_format | dspace |
| spelling | INTA13452019-03-22T14:29:57Z Clostridium perfringens epsilon toxin induces permanent neuronal degeneration and behavioral changes Morris, Winston Eduardo Goldstein, Jorge Redondo, Leandro Martín Cangelosi, Adriana Geoghegan, Patricia Brocco, Marcela Adriana Loidl, Fabián C. Fernandez Miyakawa, Mariano Enrique Enfermedades de los Animales Clostridium Perfringens Toxinas Enterotoxemia Trastornos del Sistema Nervioso Animal Diseases Toxins Enterotoxaemia Nervous System Diseases 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 2017-09-28T12:55:41Z 2017-09-28T12:55:41Z 2017-05 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion 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 eng info:eu-repo/semantics/restrictedAccess application/pdf Toxicon 130 :19-28. (May 2017) |
| spellingShingle | Enfermedades de los Animales Clostridium Perfringens Toxinas Enterotoxemia Trastornos del Sistema Nervioso Animal Diseases Toxins Enterotoxaemia Nervous System Diseases Morris, Winston Eduardo Goldstein, Jorge Redondo, Leandro Martín Cangelosi, Adriana Geoghegan, Patricia Brocco, Marcela Adriana Loidl, Fabián C. Fernandez Miyakawa, Mariano Enrique Clostridium perfringens epsilon toxin induces permanent neuronal degeneration and behavioral changes |
| title | 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_short | Clostridium perfringens epsilon toxin induces permanent neuronal degeneration and behavioral changes |
| title_sort | clostridium perfringens epsilon toxin induces permanent neuronal degeneration and behavioral changes |
| topic | Enfermedades de los Animales Clostridium Perfringens Toxinas Enterotoxemia Trastornos del Sistema Nervioso Animal Diseases Toxins Enterotoxaemia Nervous System Diseases |
| 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 |
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