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FETAL GENE EXPRESSION IN β-AMYLOID TREATED CORTICAL NEURONS AND ITS TOXIC OR PROTECTIVE EFFECTS ON NEURONS

β-淀粉样蛋白处理的皮质神经元中的胎儿基因表达及其对神经元的毒性或保护作用

基本信息

批准号：
11680771
负责人：
UCHIDA Yoko
金额：
$ 2.3万
依托单位：
TOKYO METROPOLITAN INSTITUTE OF GERONTOLOGY
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

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11680771/
关键词：
β-amyloid neurotoxicity MAP1B fetal antigens 神経細胞死胎児性抗原

项目摘要

To define fetal genes associated with neuronal death by amyloid β protein (Aβ), we analyzed gene expression in rat cerebral cortical neurons treated with A β 1-42 peptide using macro array on which 1176 cDNAs were spotted. Seventy eight mRNAs were induced in cortical neurons treated with Aβ. Out of 78 mRNAs induced by A β treatment, 10 mRNAs were upregulated in fetal (E20 days) cerebral cortex. These genes include molecules implicated in neurite outgrowth during development or responsible for regulating neurotransmitter release. MAP1B, identified as the gene highly expressed both in fetal and in A β-treated neurons, is a component of paired helical filament in Alzheimer's brain. There are three transcripts in MAP1B.Alternative transcript started from exon 3U increased in neurons treated with A β. This transcript is translated into N-terminal Δ126 amino acid truncated MAP1B.To define the role of 2 kind of MAP1B isoforms for neurite outgrowth and neuronal death, the N-terminal truncated or full-length MAP1B were overexpressed in cortical neurons. Cortical neurons expressing the truncated form had shorten and less branched neurites than those expressing full-length form. Overexpression of truncated form did not influence the neuronal death by serum withdrawal. In contrast, overexpression of full-length form resulted in promotion of neurite outgrowth and neuronal death by serum withdrawal. These results indicated that induction of alternative transcripts of MAP1B in neurons may be a protective response in brain.

为了明确β淀粉样蛋白（Aβ）致神经元死亡的相关基因，我们用1176个cDNA点样的宏芯片分析了A β 1-42肽处理的大鼠大脑皮层神经元的基因表达。在Aβ处理的皮层神经元中诱导了78种mRNA。在A β处理诱导的78个mRNA中，10个mRNA在胎儿（E20天）大脑皮质中上调。这些基因包括在发育过程中参与神经突生长或负责调节神经递质释放的分子。MAP 1B是阿尔茨海默病脑内成对螺旋丝的组成部分，在胎儿和A β处理的神经元中都有高表达。MAP 1B基因有3种转录本，A β处理组从外显子3U开始的选择性转录本增加。为了明确两种MAP 1B亚型在神经突起生长和神经元死亡中的作用，我们在皮层神经元中过表达了N端Δ126氨基酸截短的MAP 1B和全长的MAP 1B。表达截断形式的皮质神经元比表达全长形式的神经元具有缩短和较少分支的神经突。截短形式的过表达不影响血清戒断引起的神经元死亡。相反，过表达全长形式导致促进神经突起生长和神经元死亡的血清撤出。这些结果表明，在神经元中诱导MAP 1B的替代转录物可能是脑中的保护性反应。