More MS news articles for Aug 2001

Multiple sclerosis: Altered glutamate homeostasis in lesions correlates with oligodendrocyte and axonal damage

Annals of Neurology
Volume 50, Issue 2, 2001. Pages: 169-180
Peter Werner, PhD 1 2 4 *, David Pitt, MD 2, Cedric S. Raine, PhD 1 2 3
1Department of Neurology, Albert Einstein College of Medicine, Bronx, NY
2Department of Pathology, Albert Einstein College of Medicine, Bronx, NY
3Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY
4Department of Neurology, Beth Israel Medical Center, New York, NY
email: Peter Werner (
*Correspondence to Peter Werner, Depts. of Neurology and Pathology (Neuropathology), Albert Einstein College of Medicine, 1300 Morris Park Ave., F-121N Bronx, NY 10461


Glutamate excitotoxicity, recently demonstrated in an animal model of multiple sclerosis (MS), is evoked by altered glutamate homeostasis.

In the present study, we investigated the major regulating factors in glutamate excitotoxicity by immunohistochemistry in MS and control white matter with markers for glutamate production (glutaminase), glutamate transport (GLAST, GLT-1 and EAAT-1), glutamate metabolism (glutamate dehydrogenase [GDH] and glutamine synthetase [GS]), axonal damage (SMI 32) and CNS cell types.

Active MS lesions showed high-level glutaminase expression in macrophages and microglia in close proximity to dystrophic axons.

Correlation between glutaminase expression and axonal damage was confirmed experimentally in animals.

White matter from other inflammatory neurologic diseases displayed glutaminase reactivity, whereas normals and noninflammatory conditions showed none.

All three glutamate transporters were expressed robustly, mainly on oligodendrocytes, in normal, control and MS white matter, except for GLT-1, which showed low-level expression around active MS lesions.

GS and GDH were present in oligodendrocytes in normal and non-MS white matter but were absent from both active and chronic silent MS lesions, suggesting lasting metabolic impediments.

Thus, imbalanced glutamate homeostasis contributes to axonal and oligodendroglial pathology in MS.

Manipulation of this imbalance may have therapeutic import.

Received: 1 December 2000; Revised: 18 January 2001; Accepted: 14 March 2001