CREB is required for acquisition of ischemic tolerance in gerbil hippocampal CA1 region
CREB is required for acquisition of ischemic tolerance in gerbil hippocampal CA1 region
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DOI：
10.1046/j.1471-4159.2003.01847.x
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发表时间：
2003-08-01
影响因子：
4.7
通讯作者：
Ushio, Y
中科院分区：
文献类型：
--
作者：
Hara, T;Hamada, J;Ushio, Y
缺血耐受是预处理缺血对延迟性神经元死亡的神经保护作用，然而，这种作用的机制尚未完全了解。本实验采用CRE诱骗寡核苷酸技术，研究了沙土鼠海马CA 1区神经元CREB与缺血耐受的关系。亚致死性缺血导致CA 1区CREB磷酸化水平增加，而致死性缺血则没有。用NG 108 -15细胞进行的实验表明，在培养基中添加CRE诱饵寡核苷酸显著抑制细胞生长速率。向沙鼠脑室内注射CRE诱饵寡核苷酸可使CREB-DNA结合活性降低至对照组的38%。在诱导缺血耐受前24小时用CRE诱饵寡核苷酸预处理使CA 1神经元细胞存活率降低至对照的21%。目前的研究结果表明，CREB介导的转录系统是必要的诱导缺血耐受。
Ischemic tolerance is well known as a neuroprotective effect of pre-conditioning ischemia against delayed neuronal death, however, the mechanism or mechanisms underlying this effect are not fully understood. We investigated the relationship between CREB and ischemic tolerance in gerbil hippocampal CA1 neurons using CRE decoy oligonucleotide. Sublethal ischemia led to an increase in the level of CREB phosphorylation in CA1 regions while lethal ischemia did not. Experiments with NG108-15 cells showed that adding CRE decoy oligonucleotide to culture media significantly inhibited the cell growth rate. The administration of CRE decoy oligonucleotide into gerbil cerebral ventricle decreased CREB-DNA binding activity to 38% of the control. Pre-treatment with CRE decoy oligonucleotide 24 h before the induction of ischemic tolerance decreased CA1 neuronal cell survival to 21% of the control. The present findings suggest that a CREB-mediated transcription system is necessary for the induction of ischemic tolerance.