Kovalenko Tatiana, Osadchenko Irina, Nikonenko Alexander, Lushnikova Irina, Voronin Kirill, Nikonenko Irina, Muller Dominique, Skibo Galina
Department of Cytology, Bogomoletz Institute of Physiology, Kiev, Ukraine.
Hippocampus. 2006;16(10):814-25. doi: 10.1002/hipo.20211.
Relatively mild ischemic episode can initiate a chain of events resulting in delayed cell death and significant lesions in the affected brain regions. We studied early synaptic modifications after brief ischemia modeled in rats by transient vessels' occlusion in vivo or oxygen-glucose deprivation in vitro and resulting in delayed death of hippocampal CA1 pyramidal cells. Electron microscopic analysis of excitatory spine synapses in CA1 stratum radiatum revealed a rapid increase of the postsynaptic density (PSD) thickness and length, as well as formation of concave synapses with perforated PSD during the first 24 h after ischemic episode, followed at the long term by degeneration of 80% of synaptic contacts. In presynaptic terminals, ischemia induced a depletion of synaptic vesicles and changes in their spatial arrangement: they became more distant from active zones and had larger intervesicle spacing compared to controls. These rapid structural synaptic changes could be implicated in the mechanisms of cell death or adaptive plasticity. Comparison of the in vivo and in vitro model systems used in the study demonstrated a general similarity of these early morphological changes, confirming the validity of the in vitro model for studying synaptic structural plasticity.
相对轻微的缺血事件可引发一系列事件，导致延迟性细胞死亡以及受影响脑区出现显著损伤。我们通过在体内短暂阻断血管或在体外进行氧-葡萄糖剥夺对大鼠进行短暂缺血建模，研究了短暂缺血后早期的突触变化，该短暂缺血导致海马CA1锥体细胞延迟死亡。对CA1辐射层兴奋性棘突触的电子显微镜分析显示，缺血事件后的最初24小时内，突触后致密物（PSD）的厚度和长度迅速增加，同时形成了带有穿孔PSD的凹形突触，长期来看，80%的突触联系会发生退化。在突触前终末，缺血导致突触小泡耗竭及其空间排列改变：与对照组相比，它们与活性区的距离更远，囊泡间距更大。这些快速的突触结构变化可能与细胞死亡机制或适应性可塑性有关。对本研究中使用的体内和体外模型系统的比较表明，这些早期形态学变化总体相似，证实了体外模型用于研究突触结构可塑性的有效性。
