4.4 Article

Attack of the nervous system by Clostridium perfringens Epsilon toxin: From disease to mode of action on neural cells

Journal

TOXICON
Volume 75, Issue -, Pages 122-135

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.toxicon.2013.04.003

Keywords

Clostridial toxins; Brain; White matter; Neuron; Glutamate; Pore-forming toxin

Funding

  1. Mission pour la Recherche et l'Innovation Scientifique - Delegation Generale a I'Armement (M.R.I.S/D.G.A) [UMS3415]

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Epsilon toxin (ET), produced by Clostridium perfringens types B and D, ranks among the four most potent poisonous substances known so far. ET-intoxication is responsible for enterotoxaemia in animals, mainly sheep and goats. This disease comprises several manifestations indicating the attack of the nervous system. This review aims to summarize the effects of ET on central nervous system. ET binds to endothelial cells of brain capillary vessels before passing through the blood-brain barrier. Therefore, it induces perivascular oedema and accumulates into brain. ET binding to different brain structures and to different component in the brain indicates regional susceptibility to the toxin. Histological examination has revealed nerve tissue and cellular lesions, which may be directly or indirectly caused by ET. The naturally occurring disease caused by ET-intoxication can be reproduced experimentally in rodents. In mice and rats, ET recognizes receptor at the surface of different neural cell types, including certain neurons (e.g. the granule cells in cerebellum) as well as oligodendrocytes, which are the glial cells responsible for the axons myelination. Moreover, ET induces release of glutamate and other transmitters, leading to firing of neural network. The precise mode of action of ET on neural cells remains to be determined. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.

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