权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

THE BASIC STUDIES ON THE PATHOGENESIS AND THE DIAGNOSIS OF BIPOLAR DISORDERS USING ^<31>P-MRS

双相情感障碍发病机制和^<31>P-MRS诊断的基础研究

基本信息

批准号：
04670691
负责人：
HIGUCHI Teruhiko
金额：
$ 1.28万
依托单位：
GUNMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

项目摘要

Although a lot of investigations of 5HT_2 receptor supersensitivity in affective disorders have been reported, almost findings except the direct measurement of 5HT_2 receptors in platelets of depressed patients. Recent progress in imaging modalities revolutinalizes our capacity to understand the functional changes of receptors and the 2nd messenger system in vivo. Especially, NMR spectroscopy can be developed as a tool to monitor 2nd messenger system in vivo.In this project, firstly, we investigated whether the accumulation of inositol-1-phosphate can be detected by in vivo ^<31>P-MRS.5HT_2 agonist (DOI) was found to increase the level of PME and the difference of PME peak stimulated by DOI and not stimulated can be attributed to an increase in brain I-1-P levels, although we could not get conclusive data because the number of the samples was so small that the statistical analysis has not been done yet. This increase was suppressed by the pretreatment of 5HT_2 antagonist (ketanserin).Secondly, we tried to make the rats which showed 5HT_2 receptor supersensiivity. Acute stress (immobilization stress for 1 hr) and chronic stress (immobilization for 1 hr./day for 7 days) was administered to the rats and the behavioral reoponses to the 5HT_2 agonist (DOI) were compared. As the chronic stress rats showed significant increase of head shakes comparing with the non-immobilized controls, these rats were consdered to be the model of 5HT_2 recoptor supersensitivity.Thirdly, PME/beta was detected by in vivo ^<31>P-MRS in the model rats. We could not get the conclusion so far because the experiments are still continued and the number of the samples is too small to analyze statistically. Although further experiments should be done to obtain any conclusive findings, it became clear through this project that a non invasive methodology for monitoring changes in PI turnover would be helpful to the research of affective disorders.

尽管已有大量关于情感障碍中5HT_2受体超敏性的研究报道，但除了直接测量抑郁症患者血小板中5HT_2受体外几乎没有发现。成像方式的最新进展彻底改变了我们理解体内受体和第二信使系统功能变化的能力。特别是，NMR波谱可以开发为监测体内第二信使系统的工具。在这个项目中，首先，我们研究了是否可以通过体内^<31>P-MRS检测到肌醇-1-磷酸的积累。发现5HT_2激动剂（DOI）会增加PME的水平，并且受DOI刺激和未刺激的PME峰的差异可归因于脑部的增加 I-1-P水平，虽然我们无法获得结论性数据，因为样本数量太少，尚未进行统计分析。这种增加可以通过5HT_2拮抗剂(酮色林)的预处理来抑制。其次，我们尝试使大鼠表现出5HT_2受体超敏性。对大鼠施加急性应激（固定应激1小时）和慢性应激（每天固定1小时，持续7天），并比较对5HT_2激动剂（DOI）的行为反应。由于慢性应激大鼠与非固定对照组相比头部摇头显着增加，因此这些大鼠被认为是5HT_2受体超敏模型。第三，通过体内^ 31 P-MRS检测模型大鼠中的PME/β。由于实验仍在继续，样本数量太少，无法进行统计分析，所以目前还无法得出结论。尽管还需要进行进一步的实验才能获得结论性的结果，但通过该项目可以清楚地看出，监测 PI 周转变化的非侵入性方法将有助于情感障碍的研究。