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- Title
Epsilon toxin from C lostridium perfringens acts on oligodendrocytes without forming pores, and causes demyelination.
- Authors
Wioland, Laetitia; Dupont, Jean‐Luc; Doussau, Frédéric; Gaillard, Stéphane; Heid, Flavia; Isope, Philippe; Pauillac, Serge; Popoff, Michel R.; Bossu, Jean‐Louis; Poulain, Bernard
- Abstract
Epsilon toxin ( ET) is produced by C lostridium perfringens types B and D and 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 and astrocytes, we found that ET (10−9 M and 10−7 M) binds to oligodendrocytes, but not to astrocytes. ET induces an increase in extracellular glutamate, and produces oscillations of intracellular Ca2+ concentration in oligodendrocytes. These effects occurred without any change in the transmembrane resistance of oligodendrocytes, underlining that ET acts through a pore-independent mechanism. Pharmacological investigations revealed that the Ca2+ oscillations are caused by the ET-induced rise in extracellular glutamate concentration. Indeed, the blockade of metabotropic glutamate receptors type 1 ( mGluR1) prevented ET-induced Ca2+ signals. Activation of the N-methyl- D-aspartate receptor ( NMDA-R) is also involved, but to a lesser extent. Oligodendrocytes are responsible for myelinating neuronal axons. Using organotypic cultures of cerebellar slices, we found that ET induced the demyelination of Purkinje cell axons within 24 h. As this effect was suppressed by antagonizing mGluR1 and NMDA-R, demyelination is therefore caused by the initial ET-induced rise in extracellular glutamate concentration. This study reveals the novel possibility that ET can act on oligodendrocytes, thereby causing demyelination. Moreover, it suggests that for certain cell types such as oligodendrocytes, ET can act without forming pores, namely through the activation of an undefined receptor-mediated pathway.
- Subjects
TOXINS; CLOSTRIDIUM perfringens; WHITE matter (Nerve tissue); OLIGODENDROGLIA; ASTROCYTES; ASPARTATE receptors; DEMYELINATION; PURKINJE cells
- Publication
Cellular Microbiology, 2015, Vol 17, Issue 3, p369
- ISSN
1462-5814
- Publication type
Article
- DOI
10.1111/cmi.12373