Dendritic spines lost during glutamate receptor activation reemerge at original sites of synaptic contact
Dendritic spines lost during glutamate receptor activation reemerge at original sites of synaptic contact
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DOI：
10.1523/jneurosci.21-07-02393.2001
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发表时间：
2001-04-01
影响因子：
5.3
通讯作者：
Goldberg, MP
中科院分区：
文献类型：
--
作者：
Hasbani, MJ;Schlief, ML;Goldberg, MP
在脑缺血期间，神经元经历由局灶性肿胀和棘丢失组成的树突结构的快速改变。我们使用延时显微镜来确定短暂的，亚致死的缺氧或兴奋性毒性暴露后消失的树突棘的命运。在表达黄色荧光蛋白或用荧光膜示踪剂DiI标记的培养的皮质神经元中评估树突和棘形态。暴露于NMDA、红藻氨酸或氧-葡萄糖剥夺的神经元经历节段性树突珠化和大约一半树突棘的损失。在局部树突肿胀的区域观察到大多数棘丢失。尽管广泛的损失，脊髓恢复后2小时内终止激动剂暴露或氧-葡萄糖剥夺，并保持稳定，在随后的24小时内，恢复慢于AMPA/红藻氨酸受体激活后NMDA。延时荧光成像显示，绝大多数棘在它们消失的同一位置重新出现。除了棘恢复，阐述树突丝状伪足观察到新的位置沿着树突轴后，树突恢复。脊柱恢复不依赖于肌动蛋白聚合，因为它不被应用latrunculin-A，消除丝状肌动蛋白染色的脊柱和阻止脊柱运动。在整个脊柱丢失和恢复过程中，突触前和突触后元件保持物理接近。这些结果表明，树突棘的消除不一定与突触接触的丧失有关。短暂性脑缺血后，存活神经元树突棘突触的快速重建可能是功能恢复的基础。
During cerebral ischemia, neurons undergo rapid alterations in dendritic structure consisting of focal swelling and spine loss. We used time-lapse microscopy to determine the fate of dendritic spines that disappeared after brief, sublethal hypoxic or excitotoxic exposures. Dendrite and spine morphology were assessed in cultured cortical neurons expressing yellow fluorescent protein or labeled with the fluorescent membrane tracer, DiI, Neurons exposed to NMDA, kainate, or oxygen-glucose deprivation underwent segmental dendritic beading and loss of approximately one-half of dendritic spines. Most spine loss was observed in regions of local dendritic swelling. Despite widespread loss, spines recovered within 2 hr after termination of agonist exposure or oxygen-glucose deprivation and remained stable over the subsequent 24 hr, Recovery was slower after NMDA than AMPA/kainate receptor activation. Time-lapse fluorescence imaging showed that the vast majority of spines reemerged in the same location from which they disappeared. In addition to spine recovery, elaboration of dendritic filopodia was observed in new locations along the dendritic shaft after dendrite recovery. Spine recovery did not depend on actin polymerization because it was not blocked by application of latrunculin-A, which eliminated filamentous actin staining in spines and blocked spine motility. Throughout spine loss and recovery, presynaptic and postsynaptic elements remained in physical proximity. These results suggest that elimination of dendritic spines is not necessarily associated with loss of synaptic contacts. Rapid reestablishment of dendritic spine synapses in surviving neurons may be a substrate for functional recovery after transient cerebral ischemia.