Neurology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Correspondence:
Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Correspondence are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pitt, D.
Right arrow Articles by Raine, C. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pitt, D.
Right arrow Articles by Raine, C. S.
Related Collections
Right arrow Multiple sclerosis
NEUROLOGY 2003;61:1113-1120
© 2003 American Academy of Neurology

Glutamate uptake by oligodendrocytes

Implications for excitotoxicity in multiple sclerosis

David Pitt, MD, Iris E. Nagelmeier, Heather C. Wilson, MD and Cedric S. Raine, PhD

From the Departments of Neurology (Drs. Pitt and Raine), Pathology (Drs. Pitt, Wilson, and Raine, I.E. Nagelmeier), and Neuroscience (Dr. Raine), Albert Einstein College of Medicine, Bronx, NY.

Address correspondence and reprint requests to Dr. D. Pitt, Department of Neurology, Albert Einstein College of Medicine, 1300 Morris Park Ave., F-140, Bronx, NY 10461; e-mail: dfpitt{at}yahoo.com

Background: Excitotoxic damage is a common pathologic event in a number of neurologic diseases occurring after accumulation of excess extracellular glutamate in the CNS and subsequent overstimulation of glutamate receptors. In gray matter, astrocytes take up synaptically released glutamate and are thus key cells in maintaining glutamate homeostasis. In white matter, oligodendrocytes have been shown to express glutamate transporters, but their role in extracellular glutamate removal is unclear.

Objective: To investigate whether cultured human fetal oligodendrocytes functionally express the main glutamate transporters EAAT-1 and EAAT-2.

Methods: Cultures of fetal human oligodendrocytes were examined by immunocytochemistry and [3H]glutamate uptake, and the findings were correlated with glutamate transporter expression in normal and multiple sclerosis (MS) CNS tissue.

Results: Both EAAT-1 and EAAT-2 were expressed by human oligodendrocytes in vitro. Incubation of oligodendrocytes with the proinflammatory cytokine tumor necrosis factor-{alpha} (TNF{alpha}) reduced EAAT-1 expression and inhibited glutamate uptake by >75%. Furthermore, in normal human white matter, oligodendrocytes were found to be the predominant cells to express EAAT-1 and EAAT-2, both at the mRNA and at the protein level. A small number of astrocytes in white matter expressed these receptors, more so EAAT-1 than EAAT-2. In MS white matter, oligodendrocytes lost expression of EAAT-1 and EAAT-2 receptors in the lesion vicinity.

Conclusions: Oligodendrocytes appear to be predominant cells for glutamate clearance in human white matter. Glutamate receptor expression and glutamate removal were defective in MS white matter, possibly mediated by TNF{alpha}, changes that might underlie high extracellular glutamate and an increased risk for glutamate excitotoxicity.

Received May 8, 2003. Accepted in final form July 2, 2003.




This article has been cited by other articles:


Home page
 Arch. Dis. Child. Fetal Neonatal Ed.Home page
O Khwaja and J J Volpe
Pathogenesis of cerebral white matter injury of prematurity
Arch. Dis. Child. Fetal Neonatal Ed., March 1, 2008; 93(2): F153 - F161.
[Abstract] [Full Text] [PDF]

Home page
 Mult SclerHome page
R.E. Gonsette
Review: Oxidative stress and excitotoxicity: a therapeutic issue in multiple sclerosis?
Multiple Sclerosis, January 1, 2008; 14(1): 22 - 34.
[Abstract] [PDF]

Home page
 Hum Mol GenetHome page
R. Zivadinov, B. Weinstock-Guttman, R. Benedict, M. Tamano-Blanco, S. Hussein, N. Abdelrahman, J. Durfee, and M. Ramanathan
Preservation of gray matter volume in multiple sclerosis patients with the Met allele of the rs6265 (Val66Met) SNP of brain-derived neurotrophic factor
Hum. Mol. Genet., November 15, 2007; 16(22): 2659 - 2668.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Domercq, M. V. Sanchez-Gomez, C. Sherwin, E. Etxebarria, R. Fern, and C. Matute
System xc- and Glutamate Transporter Inhibition Mediates Microglial Toxicity to Oligodendrocytes
J. Immunol., May 15, 2007; 178(10): 6549 - 6556.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
E. Alberdi, M. V. Sanchez-Gomez, I. Torre, M. Domercq, A. Perez-Samartin, F. Perez-Cerda, and C. Matute
Activation of kainate receptors sensitizes oligodendrocytes to complement attack.
J. Neurosci., March 22, 2006; 26(12): 3220 - 3228.
[Abstract] [Full Text] [PDF]

Home page
 J Child NeurolHome page
F. E. Jensen
Role of Glutamate Receptors in Periventricular Leukomalacia
J Child Neurol, December 1, 2005; 20(12): 950 - 959.
[Abstract] [PDF]

Home page
 BrainHome page
R. Srinivasan, N. Sailasuta, R. Hurd, S. Nelson, and D. Pelletier
Evidence of elevated glutamate in multiple sclerosis using magnetic resonance spectroscopy at 3 T
Brain, May 1, 2005; 128(5): 1016 - 1025.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2003 by AAN Enterprises, Inc.