Basic research on the diagnosis and therapy for abnormal brain aging caused by oxidative stress.

氧化应激引起的脑异常衰老的诊断和治疗的基础研究。

基本信息

批准号：
09670930
负责人：
FUJIBAYASHI Yasuhisa
金额：
$ 1.86万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670930/
关键词：
senescense Mitochondria memory deterioration oxidative stress positron CT Cu-ATSM DNA deletion Cu-62 虚血性疾患ラジカル PCR

项目摘要

As a marker of increased oxidative stressin the brain of Senescence Accerelated Model mice P8 prone (SAMP8), mitochnodrial DNA deletion was evaluatedusing polymerase chain reaction (PCR). In addition, responsible site in mitochondrial electron transport chain was identified using mitochondrial fraction isolated from SAMP8 brain. In SAMP8 brain, significant increase in mitochondrial DNA deletion was found when compared with resistant prone (SAMR1) brain, even in pre-symptomatic young age. In SAMP8 brain, hyper activity of mitohcondrial respiration with lower respiration control ration than SAMR1. Thus, it can be said that an inefficient hyperactive state exists in the mitochondrial electron transport chain before the age-associated dysfunction develops.Using SAMP8 and SAMR1, the possibility of oxidative stress diagnosis in the brain was clarified using positron emitting radiopharmaceutical, Cu-ATSM.In SAMP8 brain, a novel hypoxia marker Cu-ATSM, which can detect the failure of electron transport using positron emission tomography (PET), highly retained than in SAMR1.Base on these finding, pre-clinical studies were started under the guide line of the Ethical Committee of our university. In normal volunteers, Cu-ATSM showed no significant accumulation in normal tissues, except for metabolic excretion organs, as well as no apparent side-effect. Then, as a first clinical trial, ischemic heart disease and tumor patients were diagnosed and clear image of unstable angina and lung tumor could be obtained.Independent from these findings, we found the interpatient differences in the brain accumulation of Cu-PTSM, a derivative of Cu-ATSM in various brain diseases. Possible relationship between mental levels and Cu-ATSM accumulation will be a next focus of the study.

作为增加氧化应激的标志物，衰老加速模型小鼠P8易P8（SAMP8）的大脑，评估了线粒体DNA缺失，从而评估了聚合酶链反应（PCR）。此外，使用从SAMP8脑分离的线粒体分数鉴定了线粒体电子传输链中的负责位点。在SAMP8脑中，与耐药性易发（SAMR1）脑相比，即使在症状前年轻的年龄，也发现线粒体DNA缺失的显着增加。在SAMP8脑中，与SAMR1相比，Mitohcondrial呼吸具有低呼吸控制评分的超活性。 Thus, it can be said that an inefficient hyperactive state exists in the mitochondrial electron transport chain before the age-associated dysfunction develops.Using SAMP8 and SAMR1, the possibility of oxidative stress diagnosis in the brain was clarified using positron emitting radiopharmaceutical, Cu-ATSM.In SAMP8 brain, a novel hypoxia marker Cu-ATSM, which can detect the failure of electron transport using正电子发射断层扫描（PET），比SAMR1中的高度保留。在这些发现的基础上，临床前研究开始于我们大学的道德委员会的指南。在正常志愿者中，除代谢排泄器官外，CU-ATSM在正常组织中没有明显的积累，没有明显的副作用。然后，作为第一次临床试验，可以诊断出缺血性心脏病和肿瘤患者，并且可以获得不稳定的心绞痛和肺部肿瘤的清晰图像。从这些发现中，我们发现Cu-PTSM的大脑插入室插入术差异，Cu-PTSM的插入术差异，Cu-PTSM的衍生物是各种脑部疾病中CU-ATM的衍生物。精神水平与Cu-ATM积累之间的可能关系将是研究的下一个重点。