Glutamate Receptor-Mediated Toxicity in Optic Nerve Oligodendrocytes

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 94; no. 16; pp. 8830 - 8835
• Main Authors: Matute, Carlos, Sanchez-Gomez, M. Victoria, Martinez-Millan, Luis, Miledi, Ricardo
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 05.08.1997; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences of the USA
• Subjects: AMPA receptors; Animals; Biological Sciences; Cell Death - drug effects; Cells, Cultured; Excitatory Amino Acid Agonists - toxicity; Eyes & eyesight; Glutamate receptors; Kainic Acid - metabolism; Kainic Acid - toxicity; Kainic acid receptors; N methyl D aspartate receptors; Nerves; Neurology; Neurons; Oligodendroglia; Oligodendroglia - drug effects; Oligodendroglia - metabolism; Oligodendroglia - pathology; Optic nerve; Optic Nerve - metabolism; Optic Nerve - pathology; Optics; Rats; Receptors; Receptors, AMPA - metabolism; Receptors, Kainic Acid - metabolism; Signal Transduction
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.94.16.8830

In cultured oligodendrocytes isolated from perinatal rat optic nerves, we have analyzed the expression of ionotropic glutamate receptor subunits as well as the effect of the activation of these receptors on oligodendrocyte viability. Reverse transcription-PCR, in combination with immunocytochemistry, demonstrated that most oligodendrocytes differentiated in vitro express the α -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits GluR3 and GluR4 and the kainate receptor subunits GluR6, GluR7, KA1 and KA2. Acute and chronic exposure to kainate caused extensive oligodendrocyte death in culture. This effect was partially prevented by the AMPA receptor antagonist GYKI 52466 and was completely abolished by the non-N-methyl-D-aspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), suggesting that both AMPA and kainate receptors mediate the observed kainate toxicity. Furthermore, chronic application of kainate to optic nerves in vivo resulted in massive oligodendrocyte death which, as in vitro, could be prevented by coinfusion of the toxin with CNQX. These findings suggest that excessive activation of the ionotropic glutamate receptors expressed by oligodendrocytes may act as a negative regulator of the size of this cell population.