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THE ROLE OF ICER, INDUCIBLE ISOFORM OF CRE TRANSCRIPTION FACTOR ON NEURONAL SYNAPTICITY, LEARNING AND MEMORY

ICER、CRE 转录因子诱导异构体对神经元突触、学习和记忆的作用

基本信息

批准号：
11680797
负责人：
KOJIMA Nobuhiko
金额：
$ 2.37万
依托单位：
THE INSTITUTE OF PHYSICAL AND CHEMICAL RESEARCH
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

Long-term neuronal plastic changes that are thought to be a cellular basis for long-term memory are newly protein-synthesis-dependent events. During a course of the study for identification of the molecules involved in the establishment of kindling, I found that ICER (inducible cyclic AMP early repressor) mRNA was transiently up-regulated in the kindled brain after the stimulation. Furthermore, increase in ICER mRNA was also observed in the amygdala after the fear conditioning and after the conditioned fear responses. Since ICER is thought to be a repressor of CRE-mediated gene transcription, this transcription factor might be involved in the down-regulation of gene expression during neuronal plastic changes and fear learning. In the PC12 cells, ICER mRNA is induced by growth factor and dBcAMP.Overexpression of ICER attenuated neurite growth of cells after such treatments, suggesting that ICER is an important regulator for cell differentiation. Dynamic gene regulation should occur during memory consolidation, as well as during cell differentiation. DNA chip technology allows us to screen systematically the mRNAs whose levels of expression are changed during memory consolidation. I found 15 genes that are up-regulated in the amygdala after fear conditioning. Thus, changes in the expression of genes dynamically occur in the amygdala during fear conditioning. These genes might be critical for molecular mechanism of long-term memory.

长期的神经元可塑性变化被认为是长期记忆的细胞基础，是新的蛋白质合成依赖事件。在对点燃建立相关分子的研究过程中，我发现在刺激后点燃的大脑中，ICER (inducible cyclic AMP early repressor) mRNA出现了短暂的上调。此外，在恐惧条件反射和条件恐惧反应后，杏仁核中也观察到ICER mRNA的增加。由于ICER被认为是cre介导的基因转录的抑制因子，该转录因子可能参与神经元可塑性变化和恐惧学习过程中基因表达的下调。在PC12细胞中，ICER mRNA受生长因子和dBcAMP的诱导。过表达ICER后，这些处理后的细胞神经突生长减弱，表明ICER是细胞分化的重要调节因子。动态基因调控应该发生在记忆巩固和细胞分化过程中。DNA芯片技术使我们能够系统地筛选在记忆巩固过程中表达水平发生变化的mrna。我发现有15个基因在恐惧条件反射后在杏仁核中被上调。因此，在恐惧调节过程中，基因表达的变化动态地发生在杏仁核中。这些基因可能对长期记忆的分子机制至关重要。