Hara H, Onodera H, Kato H, Araki T, Kogure K
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Brain Res. 1991 Apr 5;545(1-2):87-96. doi: 10.1016/0006-8993(91)91273-4.
Changes in second messenger and neurotransmitter system receptor ligand binding induced by transient forebrain ischemia were studied in the gerbil hippocampus. The animals were allowed variable periods of recovery ranging from 2 h to 7 days after 5-min bilateral carotid artery occlusion. The binding of second messenger systems ([3H]inositol 1,4,5-trisphosphate ([3H]IP3)to inositol 1,4,5-triphosphate, [3H]forskolin to adenylate cyclase and [3H]phorbol 12,13-dibutylate to protein kinase C) and neurotransmitter receptor systems ([3H]PN200-110 to L-type calcium channels. [3H]N6-cyclohexyl-adenosine to adenosine A1 and [3H]quinuclidinyl benzilate to muscarinic cholinergic receptor) were assayed using quantitative autoradiography. In the CA1 subfield, 2 h after ischemia, [3H]IP3, [3H]forskolin, and [3H]quinuclidinyl benzilate binding activities significantly decreased by 25, 17 and 13%, respectively, though no morphological abnormalities were obvious. Six hours after ischemia, the [3H]phorbol 12,13-dibutylate binding activity in the stratum oriens of the CA1 subfield increased by 15%. One day after ischemia, [3H]PN200-110 binding activity in this subfield decreased by 26%, and 7 days after ischemia, [3H]phorbol 12,13-dibutylate and [3H]N6-cyclohexyl-adenosine receptor binding activities decreased in this subfield. In particular, at 7 days after ischemia, [3H]IP3 binding activity in the CA1 subfield showed a complete decline. In the CA3 subfield, [3H]PN200-110 binding activity decreased 2 days after ischemia, and [3H]IP3 and [3H]N6-cyclohexyl-adenosine binding activities decreased 7 days after ischemia. In the dentate gyrus, the structure of which remained histologically intact after ischemic insult, [3H]IP3 and [3H]forskolin binding activities decreased 7 days after ischemia. In contrast, the [3H]phorbol 12,13-dibutylate binding activity increased in the molecular layer of the dentate gyrus 7 days after ischemia. These results indicate that marked alteration of intracellular signal transduction precedes neuronal damage in the hippocampal CA1 subfield and that the histologically intact CA3 and dentate gyrus also shows modulated neuronal transmission after ischemia.
在沙鼠海马体中研究了短暂性前脑缺血诱导的第二信使和神经递质系统受体配体结合的变化。在双侧颈动脉闭塞5分钟后，让动物恢复不同时间段，从2小时到7天不等。使用定量放射自显影法检测第二信使系统（[3H]肌醇1,4,5 - 三磷酸（[3H]IP3）与肌醇1,4,5 - 三磷酸的结合、[3H]福斯高林与腺苷酸环化酶的结合以及[3H]佛波醇12,13 - 二丁酸酯与蛋白激酶C的结合）和神经递质受体系统（[3H]PN200 - 110与L型钙通道的结合、[3H]N6 - 环己基腺苷与腺苷A1的结合以及[3H]喹核酯与毒蕈碱胆碱能受体的结合）。在CA1亚区，缺血后2小时，[3H]IP3、[3H]福斯高林和[3H]喹核酯的结合活性分别显著下降25%、17%和13%，尽管没有明显的形态学异常。缺血后6小时，CA1亚区的梨状层中[3H]佛波醇12,13 - 二丁酸酯的结合活性增加了15%。缺血后1天，该亚区中[3H]PN200 - 110的结合活性下降了26%，缺血后7天，该亚区中[3H]佛波醇12,13 - 二丁酸酯和[3H]N6 - 环己基腺苷受体的结合活性下降。特别是在缺血后7天，CA1亚区中[3H]IP3的结合活性完全下降。在CA3亚区，缺血后2天[3H]PN200 - 110的结合活性下降，缺血后7天[3H]IP3和[3H]N6 - 环己基腺苷的结合活性下降。在齿状回中，其结构在缺血损伤后组织学上保持完整，缺血后7天[3H]IP3和[3H]福斯高林的结合活性下降。相反，缺血后7天齿状回分子层中[3H]佛波醇12,13 - 二丁酸酯的结合活性增加。这些结果表明，细胞内信号转导在海马CA1亚区神经元损伤之前发生显著改变，并且组织学上完整的CA3和齿状回在缺血后也显示出神经元传递的调节。
