Clostridium perfringens epsilon toxin induces permanent neuronal degeneration and behavioral changes
| Autor: | Winston E. Morris, Marcela Adriana Brocco, Patricia Geoghegan, Jorge Goldstein, Adriana Cangelosi, Mariano E. Fernandez-Miyakawa, Leandro M. Redondo, Fabián Loidl |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Reserpine Intermediate Filaments Ciencias de la Salud Hippocampus Apoptosis Striatum Pharmacology Toxicology Dexamethasone Rats Sprague-Dawley Mice Clostridium Perfringens 0302 clinical medicine Cerebral Cortex Neurons Riluzole Epsilon Toxin Behavior Animal Microglia Neurodegeneration Brain Neuroprotective Agents medicine.anatomical_structure Anesthesia Female Ketamine medicine.drug CIENCIAS MÉDICAS Y DE LA SALUD Neurofilament Bacterial Toxins Hypothalamus Biology Enterotoxemia Lethal Dose 50 03 medical and health sciences medicine Animals Behavior Clostridium perfringens epsilon toxin medicine.disease Corpus Striatum Rats Enfermedades Infecciosas 030104 developmental biology nervous system Synapses 030217 neurology & neurosurgery Demyelinating Diseases |
| Zdroj: | Toxicon. 130:19-28 |
| ISSN: | 0041-0101 |
| Popis: | 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. Fil: Morris, Winston E.. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; Argentina Fil: Goldstein Raij, Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Redondo, Leandro Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; Argentina Fil: Cangelosi, Adriana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; Argentina Fil: Geoghegan, Patricia. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; Argentina Fil: Brocco, Marcela Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina Fil: Loidl, Cesar Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina Fil: Fernandez Miyakawa, Mariano Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; Argentina |
| Databáze: | OpenAIRE |
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