Park J S, Bateman M C, Goldberg M P
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Neurobiol Dis. 1996;3(3):215-27. doi: 10.1006/nbdi.1996.0022.
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.
突触后神经元树突的选择性退化是中风及其他神经疾病中脑损伤的病理标志。我们研究了从小鼠新皮层分离的原代培养物中的树突损伤。使用荧光膜示踪剂Dil或针对树突特异性微管相关蛋白MAP2的抗体进行免疫荧光观察神经元形态。缺氧和无糖处理30 - 60分钟导致节段性树突串珠化或膨体形成，以及树突棘丢失。这种树突损伤模式可被添加选择性NMDA拮抗剂阻断，并在暴露于10 - 100微摩尔/升NMDA的5分钟内重现。即使暴露于缺氧无糖或NMDA环境，导致第二天几乎没有神经元死亡，广泛的树突膨体形成仍会发生。尽管几乎所有神经元都出现了明显的结构变化，但在终止亚致死性缺氧无糖处理或NMDA应用后的2小时内，树突形状恢复正常。树突结构的快速、可逆变化可能在生理或病理条件下谷氨酸受体刺激后导致神经元功能改变。
