GLUTAMATE RECEPTOR-MEDIATED TOXICITY IN OPTIC-NERVE OLIGODENDROCYTES

In cultured oligodendrocytes isolated from perinatal rat optic nerves, we have analyzed the expression of ionotropic glutamate receptor subu nits as well as the effect of the activation of these receptors on oli godendrocyte viability, Reverse transcription-PCR, in combination with immunocytochemistry, demonstrated that mast oligodendrocytes differen tiated in vitro express the alpha-amino3-hydroxy-5-methyl-4-isoxazolep ropionic acid (AMPA) receptor subunits GluR3 and GluR4 and the kainate receptor subunits GluR6, GluR7, KA1 and KA2, Acute and chronic exposu re to kainate caused extensive oligodendrocyte death in culture, This effect was partially prevented bg the AMPA. receptor antagonist GYKI 5 2466 and was completely abolished by the non-N-methyl-D-aspartate rece ptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), suggestin g that both AMPA and kainate receptors mediate the observed kainate to xicity, Furthermore, chronic application of kainate to optic nerves in vivo resulted in massive oligodendrocyte death which, as in vitro, co uld be prevented qv coinfusion of the toxin with CNQX, These findings suggest that excessive activation of the ionotropic glutamate receptor s expressed by oligodendrocytes mag act as a negative regulator of the size of this cell population.