Epsilon toxin from C lostridium perfringens acts on oligodendrocytes without forming pores, and causes demyelination - Institut Pasteur Access content directly
Journal Articles Cellular Microbiology Year : 2015

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

Abstract

Epsilon toxin (ET) is produced by Clostridium 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 Ca(2+) 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 Ca(2+) 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 Ca(2+) 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.

Domains

Toxicology
Fichier principal
Vignette du fichier
Wioland_et_al-2015-Cellular_Microbiology.pdf (1.63 Mo) Télécharger le fichier
Origin : Publication funded by an institution
Loading...

Dates and versions

pasteur-01767526 , version 1 (16-04-2018)

Licence

Attribution - NonCommercial - NoDerivatives

Identifiers

Cite

Laetitia Wioland, Jean-Luc Dupont, Frédéric Doussau, Stéphane Gaillard, Flavia Heid, et al.. Epsilon toxin from C lostridium perfringens acts on oligodendrocytes without forming pores, and causes demyelination. Cellular Microbiology, 2015, 17 (3), pp.369 - 388. ⟨10.1111/cmi.12373⟩. ⟨pasteur-01767526⟩
203 View
127 Download

Altmetric

Share

Gmail Facebook X LinkedIn More