Abstract

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.

Highlights

  • The bacterial genus Clostridium comprises Grampositive anaerobic bacteria, which are present in all kinds of environments

  • Using slices of mouse cerebellum submitted to Epsilon toxin (ET) (ET being applied on acute slices or after fixation of the slices), examination of the cellular localization of ET immunostaining has revealed that the toxin binds to the cell body of cerebellar granule cells, which are glutamatergic neurons (Fig. 1A and C)

  • ET has the fundamental structure of a pore-forming toxin, and it is expected to interact with many various cell types

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Summary

Introduction

The bacterial genus Clostridium comprises Grampositive anaerobic bacteria, which are present in all kinds of environments. Symptoms and manifestations observed either in the naturally occurring disease or after experimental intoxication (i.e. either by injecting C. perfringens in the gastrointestinal tract or ET in the duodenum, intraperitoneally or intravenously) can be sorted into groups according to the altered-physiological system: intestinal, renal, pulmonary and nervous systems.

From intestine to brain tissue
Tissular and cellular lesions in the central nervous system
ET binds to a subset of neurons
Binding of ET to oligodendrocytes
Does ET bind onto nerve terminals?
The mechanisms by which ET acts on neural cells
Binding to its receptor
Oligomerization
The pore formed by ET
Role of cholesterol
Causal linkage between formation of ET-pore and cytotoxicity
ET as an excitatory neurotoxin
Conclusion
Conflict of interest
Full Text
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