[3H]Muscimol Binding to &ggr;-Aminobutyric AcidA Receptors Is Upregulated in CA1 Neurons of the Gerbil Hippocampus in the Ischemia-Tolerant State
[3H]Muscimol Binding to &ggr;-Aminobutyric AcidA Receptors Is Upregulated in CA1 Neurons of the Gerbil Hippocampus in the Ischemia-Tolerant State
复制标题
[3H]蝇蕈醇结合
DOI：
10.1161/01.str.0000016404.14407.77
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
M. Kiessling
中科院分区：
文献类型：
--
作者：
C. Sommer;A. Fahrner;M. Kiessling
背景和目的-谷氨酸受体的兴奋毒性激活目前被认为在短暂性全脑缺血后沙土鼠海马区高度脆弱的CA1神经元迟发性神经元死亡(DND)中起关键作用。这些神经元的缺血后变性可以通过“预适应”和短暂的亚致死性缺血刺激来预防。本研究旨在检测缺血预适应是否与与兴奋性谷氨酸和/或抑制性氨基丁酸(GABA；)A受体结合的配体的特异性改变有关，与严重到足以诱发DND的缺血相比。方法：采用定量受体放射自显影技术，分析了脑缺血后[3 H]MK 80 1、[3H]&agr；-amino-3-hydroxy-5-methyl-4-isoxazole丙酸(AMPA)与兴奋性N-甲基-d-天冬氨酸(N-甲基-D-天冬氨酸)和AMPA受体的结合，以及[3 H]蝇草醇与海马CA1、CA3区和齿状回GABA受体的抑制作用。沙土鼠经历(1)5分钟的缺血期导致CA1神经元的DND和(2)2.5分钟的缺血期介导耐受诱导。结果-[~3H]MK-801和[~H]AMPA与兴奋性NMDA和AMPA受体的结合值显示，尽管神经元细胞密度保持不变，但相对耐缺血的CA3和齿状回的结合值仍有延迟性下降。预适应后，CA1区神经元与GABAA受体的结合一过性增加，但在神经元连续死亡的全脑缺血后无明显变化。结论--在相对耐缺血的CA3和齿状回神经元中，与谷氨酸受体结合的配体的下调表明，尽管结构保持完整，但突触重组过程显著。更重要的是，海马区抑制性GABAA受体的结合上调表明抑制性和兴奋性神经传递之间的相对转变，我们认为这可能参与了内源性缺血后神经保护。
Background and Purpose— Excitotoxic activation of glutamate receptors is currently thought to play a pivotal role in delayed neuronal death (DND) of highly vulnerable CA1 neurons in the gerbil hippocampus after transient global ischemia. Postischemic degeneration of these neurons can be prevented by “preconditioning” with a short sublethal ischemic stimulus. The present study was designed to test whether ischemic preconditioning is associated with specific alterations of ligand binding to excitatory glutamate and/or inhibitory &ggr;-aminobutyric acid (GABA)A receptors compared with ischemia severe enough to induce DND. Methods— With the use of quantitative receptor autoradiography, postischemic ligand binding of [3H]MK-801 and [3H]&agr;-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) to excitatory N-methyl-d-aspartate (NMDA) and AMPA receptors as well as [3H]muscimol to inhibitory GABAA receptors in hippocampal subfields CA1, CA3, and the dentate gyrus were analyzed in 2 experimental paradigms. Gerbils were subjected to (1) a 5-minute ischemic period resulting in DND of CA1 neurons and (2) a 2.5-minute period of ischemia mediating tolerance induction. Results— [3H]MK-801 and [3H]AMPA binding values to excitatory NMDA and AMPA receptors showed a delayed decrease in relatively ischemia-resistant CA3 and dentate gyrus despite maintained neuronal cell density. [3H]Muscimol binding to GABAA receptors in CA1 neurons was transiently but significantly increased after preconditioning but not after global ischemia with consecutive neuronal death. Conclusions— Downregulation of ligand binding to glutamate receptors in relatively ischemia-resistant CA3 and dentate gyrus neurons destined to survive suggests marked synaptic reorganization processes despite maintained structural integrity. More importantly, upregulation of binding to inhibitory GABAA receptors in the hippocampus indicates a relative shift between inhibitory and excitatory neurotransmission that we suggest may participate in endogenous postischemic neuroprotection.