Rapid Alterations in Dendrite Morphology during Sublethal Hypoxia or Glutamate Receptor Activation

Abstract

Selective degeneration of postsynaptic neuronal dendrites is a pathological hallmark of brain injury in stroke and other neurological disorders. We examined dendritic injury in primary cultures dissociated from mouse neocortex. Neuronal morphology was visualized using the fluorescent membrane tracer, Dil, or immunofluorescence with antibodies to the dendrite-specific microtubule-associated protein, MAP2. Deprivation of oxygen and glucose for 30-60 min resulted in segmental dendritic beading, 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 microM NMDA. Widespread 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 affecting virtually all neurons, dendrite shape returned to normal within 2 h of terminating sublethal oxygen-glucose deprivation or NMDA application. Rapid, reversible changes in dendritic structure may contribute to alterations in neuronal function following glutamate receptor stimulation under physiological or pathological conditions.