Mature myelin basic protein-expressing oligodendrocytes are insensitive to kainate toxicity.
We examined the vulnerability to excitotoxicity of rat oligodendrocytes in dissociated cell culture at different developmental stages. Mature oligodendrocytes that express myelin basic protein were resistant to excitotoxic injury produced by kainate, whereas earlier stages in the oligodendrocyte lineage were vulnerable to this insult. To test the hypothesis that the sensitivity of immature oligodendrocytes and the resistance of mature oligodendrocytes to kainate toxicity were due to differences in membrane responsiveness to kainate, we used whole-cell patch-clamp recording. Oligodendrocyte precursors in cultures vulnerable to kainate toxicity responded to 500 microM kainate with large inward currents, whereas mature myelin basic protein-expressing oligodendrocytes in cultures resistant to kainate toxicity showed no clear response to application of this agonist. We assayed expression of glutamate receptor subunits (GluR) -2, -4, -6, -7, and KA2 using immunoblot analysis and found that expression of all of these glutamate receptors was significantly down-regulated in mature oligodendrocytes. These results suggest a striking developmental regulation of glutamate receptors in oligodendrocytes and suggest that the vulnerability of oligodendrocytes to non- N-methyl-D-aspartate receptor-mediated excitotoxicity might be much greater in developing oligodendrocytes than after the completion of myelination.
Rosenberg
Paul A
PA
Department of Neurology and Program in Neuroscience, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. paul.rosenberg@tch.harvard.edu
Dai
Weimin
W
Gan
Xiao Dong
XD
Ali
Sanjida
S
Fu
Jennifer
J
Back
Stephen A
SA
Sanchez
Russell M
RM
Segal
Michael M
MM
Follett
Pamela L
PL
Jensen
Frances E
FE
Volpe
Joseph J
JJ
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004347:Drug Interactions; D004594:Electrophysiology / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D015151:Immunoblotting; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000494:pharmacology*; D004676:Myelin Basic Protein / Q000187:drug effects / Q000378:metabolism*; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000145:classification / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D020934:Ciliary Neurotrophic Factor; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D004676:Myelin Basic Protein; D010982:Platelet-Derived Growth Factor; D017470:Receptors, Glutamate; C075278:platelet-derived growth factor A; D005346:Fibroblast Growth Factors; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid