RAPID ALTERATIONS IN DENDRITE MORPHOLOGY DURING SUBLETHAL HYPOXIA OR GLUTAMATE-RECEPTOR ACTIVATION

Selective degeneration of postsynaptic neuronal dendrites is a patholo gical hallmark of brain injury in stroke and other neurological disord ers. We examined dendritic injury in primary cultures dissociated from mouse neocortex. Neuronal morphology was visualized using the fluores cent membrane tracer, Dil, or immunofluorescence with antibodies to th e dendrite-specific microtubule-associated protein, MAPS. Deprivation of oxygen and glucose for 30-60 min resulted in segmental dendritic be ading, or varicosities, and loss of dendritic spines. This pattern of dendritic injury was blocked by addition of selective NMDA antagonists , and was reproduced within 5 min of exposure to 10-100 mu M NMDA. Wid espread dendritic varicosity formation occurred even with exposures to oxygen-glucose deprivation or NMDA which resulted in little neuronal death by the following day. Despite marked structural changes affectin g virtually all neurons, dendrite shape returned to normal within 2 h of terminating sublethal oxygen-glucose deprivation or NMDA applicatio n. Rapid, reversible changes in dendritic structure may contribute to alterations in neuronal function following glutamate receptor stimulat ion under physiological or pathological conditions. (C) 1996 Academic Press, Inc.