NMDA receptors mediate hypoxic spine loss in cultured neurons.

We examined the pharmacology of dendritic morphologic changes in cultured cortical neurons exposed to sublethal oxygen-glucose deprivation (OGD). Confocal analysis of DiI-labeled neurons demonstrated transient dendritic swelling and spine loss after OGD. These morphological changes were reproduced by direct application of NMDA, kainate, veratridine, ionomycyin, and gramicidin, but not KCl. Blockade of voltage-gated sodium or calcium channels did not prevent OGD-induced dendritic spine loss. In contrast, the NMDA receptor antagonist, MK-801, fully prevented these changes. An AMPA/kainate receptor antagonist, NBQX, had no effect by itself but reduced spine loss when added to MK-801. While alterations in dendrite morphology may be triggered by activation of disparate ion channels, rapid spine loss in hypoxic cortical neurons is mediated preferentially through activation of the NMDA subtype glutamate receptor.