title: Distribution of Clostridium perfringens epsilon toxin in the brains of acutely intoxicated mice and its effect upon glial cells.
abstract: Epsilon toxin (epsilon-toxin), produced by Clostridium perfringens types B and D, causes fatal enterotoxaemia in livestock. The disease is principally manifested as severe and often fatal neurological disturbance. Oedema of several organs, including the brain, is also a clinical sign related to microvascular damage. Recombinant epsilon-toxin-green fluorescence protein (epsilon-toxin-GFP) and epsilon-prototoxin-GFP have already been characterised as useful tools to track their distribution in intravenously injected mice, by means of direct fluorescence microscopy detection. The results shown here, using an acutely intoxicated mouse model, strongly suggest that epsilon-toxin-GFP, but not epsilon-prototoxin-GFP, not only causes oedema but is also able to cross the blood-brain barrier and accumulate in brain tissue. In some brain areas, epsilon-toxin-GFP is found bound to glial cells, both astrocytes and microglia. Moreover, cytotoxicity assays, performed with mixed glial primary cultures, demonstrate the cytotoxic effect of epsilon-toxin upon both astrocytes and microglial cells.
authors.affiliation: Laboratori de Neurobiologia Cellular i Molecular, Departament de Patologia i Terapèutica Experimental, Campus de Bellvitge, Universitat de Barcelona-IDIBELL, Spain.
authors.forename: Alex
authors.initials: A
authors.lastname: Soler-Jover
authors.forename: Jonatan
authors.initials: J
authors.lastname: Dorca
authors.forename: Michel R
authors.initials: MR
authors.lastname: Popoff
authors.forename: Maryse
authors.initials: M
authors.lastname: Gibert
authors.forename: Josep
authors.initials: J
authors.lastname: Saura
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Tusell
authors.forename: Joan
authors.initials: J
authors.lastname: Serratosa
authors.forename: Juan
authors.initials: J
authors.lastname: Blasi
authors.forename: Mireia
authors.initials: M
authors.lastname: Martín-Satué
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001427:Bacterial Toxins / Q000493:pharmacokinetics* / Q000506:poisoning*; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D004730:Endothelium, Vascular / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000187:drug effects*
chemical_list: D001427:Bacterial Toxins; C039811:Clostridium perfringens epsilon-toxin; D049452:Green Fluorescent Proteins