Epsilon toxin from C lostridium perfringens acts on oligodendrocytes without forming pores, and causes demyelination

• DOI: 10.1111/cmi.12373
• Publication Date: 2014-10-07T02:23:37Z
• Authors: Laetitia Wioland; Jean‐Luc Dupont; Frédéric Doussau; Stéphane Gaillard; Flavia Heid; Philippe Isope; Serge Pauillac; Michel R. Popoff; Jean‐Louis Bossu; Bernard Poulain
• Keywords: Clostridium perfringens

Epsilon toxin (ET) is produced by Clostridium perfringens types B and D causes severe neurological disorders in animals. ET has been observed binding to white matter, suggesting that it may target oligodendrocytes. In primary cultures containing oligodendrocytes astrocytes, we found (10−9 M 10−7 M) binds oligodendrocytes, but not astrocytes. induces an increase extracellular glutamate, produces oscillations of intracellular Ca2+ concentration These effects occurred without any change the transmembrane resistance underlining acts through a pore-independent mechanism. Pharmacological investigations revealed are caused ET-induced rise glutamate concentration. Indeed, blockade metabotropic receptors type 1 (mGluR1) prevented signals. Activation N-methyl-D-aspartate receptor (NMDA-R) also involved, lesser extent. Oligodendrocytes responsible for myelinating neuronal axons. Using organotypic cerebellar slices, induced demyelination Purkinje cell axons within 24 h. As this effect was suppressed antagonizing mGluR1 NMDA-R, therefore initial This study reveals novel possibility can act on thereby causing demyelination. Moreover, suggests certain such as forming pores, namely activation undefined receptor-mediated pathway.