NMDA receptors mediate hypoxic spine loss in cultured neurons

We examined the pharmacology of dendritic morphologic changes in cultured c ortical neurons exposed to sublethal oxygen-glucose deprivation (OGD). Conf ocal analysis of Dil-labeled neurons demonstrated transient dendritic swell ing and spine loss after OGD. These morphological changes were reproduced b y direct application of NMDA, kainate, veratridine, ionomycyin, and gramici din, but not KCl. Blockade of voltage-gated sodium or calcium channels did not prevent OGD-induced dendritic spine loss. In contrast, the NMDA recepto r antagonist, MK-801, fully prevented these changes. An AMPA/kainate recept or antagonist, NBQX, had no effect by itself but reduced spine loss when ad ded 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. NeuroReport 12:2731-2735 (C) 2001 Lippincott Williams & Wilkins.