Oxygen/Glucose Deprivation and Reperfusion Cause Modifications of Postsynaptic Morphology and Activity in the CA3 Area of Organotypic Hippocampal Slice Cultures.
Oxygen/Glucose Deprivation and Reperfusion Cause Modifications of Postsynaptic Morphology and Activity in the CA3 Area of Organotypic Hippocampal Slice Cultures.
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DOI：
10.4196/kjpp.2012.16.6.423
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发表时间：
2012-12
期刊：
影响因子：
--
通讯作者：
Lee KE
中科院分区：
文献类型：
--
作者：
Jung YJ;Suh EC;Lee KE
脑缺血导致N-甲基-D-天冬氨酸（NMDA）受体的过度刺激，称为兴奋性毒性，其介导神经元细胞死亡。然而，很少有人注意到突触活动和形态学的变化，可能有一个重要的影响，细胞功能和生存缺血性损伤。在这项研究中，我们研究了氧/葡萄糖剥夺（OGD）后再灌注的影响，不仅对神经元细胞死亡，而且对突触后密度（PSD）蛋白的超微结构和生化特性，在透明层的CA 3区的器官型海马切片培养。OGD/再灌注后，神经元受损，线粒体、内质网、树突、突触终末等细胞器肿胀，PSD增厚、不规则。乙醇磷钨酸染色显示，与对照组相比，OGD/再灌注组PSD密度显著降低，PSD厚度和长度显著增加。PSD蛋白，包括PSD-95，NMDA受体1，NMDA受体2B和钙/钙调素依赖性蛋白激酶II的水平，在OGD/再灌注后显著降低。这些结果表明，OGD/再灌注诱导显著修改PSD在CA 3区的器官型海马切片培养物，形态学和生化，这可能有助于神经元细胞死亡和突触功能障碍后OGD/再灌注。
Brain ischemia leads to overstimulation of N-methyl-D-aspartate (NMDA) receptors, referred as excitotoxicity, which mediates neuronal cell death. However, less attention has been paid to changes in synaptic activity and morphology that could have an important impact on cell function and survival following ischemic insult. In this study, we investigated the effects of reperfusion after oxygen/glucose deprivation (OGD) not only upon neuronal cell death, but also on ultrastructural and biochemical characteristics of postsynaptic density (PSD) protein, in the stratum lucidum of the CA3 area in organotypic hippocampal slice cultures. After OGD/reperfusion, neurons were found to be damaged; the organelles such as mitochondria, endoplasmic reticulum, dendrites, and synaptic terminals were swollen; and the PSD became thicker and irregular. Ethanolic phosphotungstic acid staining showed that the density of PSD was significantly decreased, and the thickness and length of the PSD were significantly increased in the OGD/reperfusion group compared to the control. The levels of PSD proteins, including PSD-95, NMDA receptor 1, NMDA receptor 2B, and calcium/calmodulin-dependent protein kinase II, were significantly decreased following OGD/reperfusion. These results suggest that OGD/reperfusion induces significant modifications to PSDs in the CA3 area of organotypic hippocampal slice cultures, both morphologically and biochemically, and this may contribute to neuronal cell death and synaptic dysfunction after OGD/reperfusion.
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DOI：
10.1002/neu.480230915
发表时间：
1992-11-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
CHOI, DW
通讯作者：
CHOI, DW
影响因子：
4.7
作者：
GOLDENRING, JR;MCGUIRE, JS;DELORENZO, RJ
通讯作者：
DELORENZO, RJ
影响因子：
6.3
作者：
KIRINO, T;ROBINSON, HPC;KAWAI, N
通讯作者：
KAWAI, N
影响因子：
8.3
作者：
Bolay, H;Gürsoy-Özdemir, Y;Dalkara, T
通讯作者：
Dalkara, T
影响因子：
2.3
作者：
Aoki, C;Miko, I;Bredt, DS
通讯作者：
Bredt, DS