Premium
Excitotoxic oligodendrocyte death and axonal damage induced by glutamate transporter inhibition
Author(s) -
Domercq María,
Etxebarria Estibaliz,
PérezSamartín Alberto,
Matute Carlos
Publication year - 2005
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20221
Subject(s) - excitotoxicity , glutamate receptor , biology , kainate receptor , oligodendrocyte , ampa receptor , kainic acid , transporter , microbiology and biotechnology , neuroscience , pharmacology , myelin , biochemistry , central nervous system , receptor , gene
Glutamate uptake is crucial to terminate glutamate signaling and to prevent excitotoxicity. The present study describes the expression of functional glutamate transporters GLAST and GLT‐1 in oligodendrocytes by means of electrophysiology, uptake assays, and immunocytochemistry. Inhibition of glutamate uptake, both in oligodendrocyte cultures and in isolated optic nerves, increases glutamate levels and causes oligodendrocyte excitotoxicity, which is prevented by alpha‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) and kainate receptor antagonists. Furthermore, glutamate transporter inhibitors or antisense oligonucleotides applied onto the optic nerve in vivo lead to oligodendroglial loss, massive demyelination, and severe axonal damage. Overall, these results demonstrate that the integrity of oligodendrocytes and white matter depends on proper glutamate transporter function. Deregulated transporter activity may contribute to acute and chronic white matter damage. © 2005 Wiley‐Liss, Inc.