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A gliotoxic factor and multiple sclerosis

A Ménard¹, R Amouri, T Dobránsky

¹INSERM, Laboratoire de Neuromodulations Interactives et Neuropathologies, Paris, France.

Journal of the Neurological Sciences

|April 30, 1998

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Cerebrospinal fluid from multiple sclerosis patients contains a toxic factor that kills glial cells. This gliotoxin may be an initial cause of multiple sclerosis pathology, including demyelination.

Area of Science:

Neuroscience
Immunology
Cell Biology

Background:

The exact cause of multiple sclerosis (MS) pathogenesis remains unknown.
Investigating potential toxic factors in MS is crucial for understanding disease mechanisms.

Purpose of the Study:

To identify and characterize cytotoxic factors in the cerebrospinal fluid (CSF) of MS patients.
To investigate the specific cell types affected by these factors and their potential role in MS pathology.

Main Methods:

In vitro exposure of various human cell types (astrocytes, oligodendrocytes, fibroblasts, etc.) to heat-treated CSF from MS patients and control groups.
Chromatographic purification of the cytotoxic factor from MS CSF.
Analysis of cellular changes indicative of apoptosis (DNA fragmentation, chromatin condensation, cell shrinkage).

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Main Results:

Heat-treated CSF from MS patients induced apoptotic death specifically in astrocytes and oligodendrocytes, but not other cell types.
CSF from non-MS neurological diseases did not exhibit toxicity.
A 17-kDa glycoprotein, termed gliotoxin, was identified as the cytotoxic factor responsible for glial cell death.

Conclusions:

A novel cytotoxic factor, gliotoxin, present in MS CSF, selectively induces apoptosis in astrocytes and oligodendrocytes.
Gliotoxin may be an initiating factor in multiple sclerosis pathogenesis, contributing to neuropathological features like demyelination and blood-brain barrier disruption.