MR: GR Balance in Depression

MR:抑郁症中的GR平衡

基本信息

  • 批准号:
    7843493
  • 负责人:
  • 金额:
    $ 38.63万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-05-15 至 2013-04-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Stress is strongly linked to depression and increased basal activation of the main stress hormone system, the hypothalamic pituitary adrenal (HPA) axis, has been found in approximately 30% of patients with major depression. Glucocorticoids act through two different receptor systems, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). Most work in depression has focused on GR with the traditional dexamethasone suppression test (DST). But, there are a number of reasons to expect that MR may be relevant for depression. Studies have suggested that the balance of MR to GR activity is important not only in regulating the HPA axis, but also particularly relevant to brain serotonin systems. Cortisol, acting through MR has been shown to regulate 5HT1a receptors, which have been shown to be down-regulated in brain in patients with major depression in both post-mortem and neuroimaging studies. Stress and increased cortisol, acting through GR, have been shown to increase 5HT2a receptors, which are also increased in patients with depression. We propose to characterize major depression in terms of MR and GR activity. Specifically, we propose: 1 To extend our previous findings of increased MR activity in subjects with major depression, as assessed by the ACTH and cortisol response to a spironolactone challenge. Based on our pilot data, we hypothesize that MR activity will be increased in patients with major depression compared to control subjects in response to both AM and PM spironolactone challenge. To determine if increased MR activity as assessed by the MR antagonist spironolactone is accompanied by decreases in GR activity is the same individuals, as assessed by the GR agonist dexamethasone, in subjects with major depression. We hypothesize that depressed patients will show GR downregulation and thus increased plasma ACTH and cortisol levels following dexamethasone challenge. Combined with enhanced MR activation, this will lead to an alteration in MR:GR balance. 3.To determine if MR dysregulation is involved in the hypercortisolemia of depression. We hypothesize that normal subjects will show increased cortisol, compared to placebo day, in response to 2 doses of spironolactone while depressed patients will show a smaller increase in response to the 2 dose spironolactone challenge. 4. To determine if MR plays a role in stress regulation in humans. We will examine response to the Trier Social stress test and determine if the there are differences in the ACTH and cortisol response to the TSST in the presence of spironolactone vs placebo. We will conduct these studies in the PM only, the time when the TSST response is most robust, and when MR is believed to play the predominant regulatory role. PUBLIC HEALTH RELEVANCE: Stress plays an important role in depression and the prototypical stress hormone, cortisol, is increased in patients with depression. Cortisol binds to 2 different receptors, MR and GR. But studies to date have only really examined GR function in depression. We propose to characterize the role of MR and the MR:GR balance in depression.
描述(由申请人提供):压力与抑郁症密切相关,在约30%的重度抑郁症患者中发现主要压力激素系统(下丘脑垂体肾上腺(HPA)轴)的基础激活增加。糖皮质激素通过两种不同的受体系统起作用,盐皮质激素受体(MR)和糖皮质激素受体(GR)。抑郁症的大多数工作都集中在GR与传统的地塞米松抑制试验(DST)。但是,有很多理由可以预期MR可能与抑郁症有关。研究表明,MR与GR活性的平衡不仅在调节HPA轴中很重要,而且与脑5-羟色胺系统特别相关。皮质醇通过MR起作用,已被证明可以调节5 HT 1a受体,在尸检和神经影像学研究中,这些受体在重度抑郁症患者的大脑中被下调。压力和皮质醇增加,通过GR起作用,已被证明增加5 HT 2a受体,这也增加了抑郁症患者。我们建议以MR和GR活性来表征抑郁症。具体而言,我们建议:1扩展我们先前的研究结果,即重度抑郁症受试者的MR活动增加,通过ACTH和皮质醇对螺内酯挑战的反应进行评估。根据我们的初步数据,我们假设,与对照组相比,抑郁症患者在AM和PM螺内酯激发时MR活动会增加。为了确定在重度抑郁症受试者中,MR拮抗剂螺内酯评估的MR活性增加是否伴随GR活性降低,与GR激动剂地塞米松评估的相同个体。我们推测抑郁症患者在地塞米松刺激后会表现出GR下调,从而增加血浆ACTH和皮质醇水平。结合增强的MR激活,这将导致MR:GR平衡的改变。3.探讨抑郁症患者高皮质醇血症是否与MR失调有关。我们假设,正常受试者将显示增加皮质醇,与安慰剂日相比,响应于2剂量的螺内酯,而抑郁症患者将显示响应于2剂量的螺内酯挑战的较小增加。4.确定MR是否在人类的压力调节中发挥作用。我们将检查对特里尔社会应激试验的反应,并确定在螺内酯与安慰剂存在下,ACTH和皮质醇对TSST的反应是否存在差异。我们将仅在PM中进行这些研究,此时TSST响应最稳健,并且认为MR发挥主要调节作用。公共卫生关系:压力在抑郁症中起着重要的作用,抑郁症患者的原型压力激素皮质醇增加。皮质醇与两种不同的受体MR和GR结合,但迄今为止的研究只真正研究了GR在抑郁症中的功能。我们建议的特点的作用,MR和MR:GR平衡在抑郁症。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Juan F Lopez其他文献

Juan F Lopez的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Juan F Lopez', 18)}}的其他基金

MR: GR Balance in Depression
MR:抑郁症中的GR平衡
  • 批准号:
    8257538
  • 财政年份:
    2009
  • 资助金额:
    $ 38.63万
  • 项目类别:
Maternal behavior and effects of paternal affiliation in 5-HT1a overexpressing mi
5-HT1a 过表达 mi 中的母亲行为和父系关系的影响
  • 批准号:
    7462642
  • 财政年份:
    2009
  • 资助金额:
    $ 38.63万
  • 项目类别:
MR: GR Balance in Depression
MR:抑郁症中的GR平衡
  • 批准号:
    8063943
  • 财政年份:
    2009
  • 资助金额:
    $ 38.63万
  • 项目类别:
Maternal behavior and effects of paternal affiliation in 5-HT1a overexpressing mi
5-HT1a 过表达 mi 中的母亲行为和父系关系的影响
  • 批准号:
    7862324
  • 财政年份:
    2009
  • 资助金额:
    $ 38.63万
  • 项目类别:
MR: GR Balance in Depression
MR:抑郁症中的GR平衡
  • 批准号:
    7646095
  • 财政年份:
    2009
  • 资助金额:
    $ 38.63万
  • 项目类别:
Stress Regulation of 5HT Receptors and the HPA Axis
5HT 受体和 HPA 轴的压力调节
  • 批准号:
    6327367
  • 财政年份:
    2001
  • 资助金额:
    $ 38.63万
  • 项目类别:
Stress Regulation of 5HT Receptors and the HPA Axis
5HT 受体和 HPA 轴的应激调节
  • 批准号:
    6879720
  • 财政年份:
    2001
  • 资助金额:
    $ 38.63万
  • 项目类别:
Stress Regulation of 5HT Receptors and the HPA Axis
5HT 受体和 HPA 轴的压力调节
  • 批准号:
    6539162
  • 财政年份:
    2001
  • 资助金额:
    $ 38.63万
  • 项目类别:
Stress Regulation of 5HT Receptors and the HPA Axis
5HT 受体和 HPA 轴的应激调节
  • 批准号:
    6639209
  • 财政年份:
    2001
  • 资助金额:
    $ 38.63万
  • 项目类别:
Stress Regulation of 5HT Receptors and the HPA Axis
5HT 受体和 HPA 轴的应激调节
  • 批准号:
    6719520
  • 财政年份:
    2001
  • 资助金额:
    $ 38.63万
  • 项目类别:

相似国自然基金

Agonist-GPR119-Gs复合物的结构生物学研究
  • 批准号:
    32000851
  • 批准年份:
    2020
  • 资助金额:
    24.0 万元
  • 项目类别:
    青年科学基金项目

相似海外基金

S1PR1 agonistによる脳血液関門制御を介した脳梗塞の新規治療法開発
S1PR1激动剂调节血脑屏障治疗脑梗塞新方法的开发
  • 批准号:
    24K12256
  • 财政年份:
    2024
  • 资助金额:
    $ 38.63万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
AHR agonistによるSLE皮疹の新たな治療薬の開発
使用 AHR 激动剂开发治疗 SLE 皮疹的新疗法
  • 批准号:
    24K19176
  • 财政年份:
    2024
  • 资助金额:
    $ 38.63万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Evaluation of a specific LXR/PPAR agonist for treatment of Alzheimer's disease
特定 LXR/PPAR 激动剂治疗阿尔茨海默病的评估
  • 批准号:
    10578068
  • 财政年份:
    2023
  • 资助金额:
    $ 38.63万
  • 项目类别:
AUGMENTING THE QUALITY AND DURATION OF THE IMMUNE RESPONSE WITH A NOVEL TLR2 AGONIST-ALUMINUM COMBINATION ADJUVANT
使用新型 TLR2 激动剂-铝组合佐剂增强免疫反应的质量和持续时间
  • 批准号:
    10933287
  • 财政年份:
    2023
  • 资助金额:
    $ 38.63万
  • 项目类别:
Targeting breast cancer microenvironment with small molecule agonist of relaxin receptor
用松弛素受体小分子激动剂靶向乳腺癌微环境
  • 批准号:
    10650593
  • 财政年份:
    2023
  • 资助金额:
    $ 38.63万
  • 项目类别:
AMPKa agonist in attenuating CPT1A inhibition and alcoholic chronic pancreatitis
AMPKa 激动剂减轻 CPT1A 抑制和酒精性慢性胰腺炎
  • 批准号:
    10649275
  • 财政年份:
    2023
  • 资助金额:
    $ 38.63万
  • 项目类别:
A randomized double-blind placebo controlled Phase 1 SAD study in male and female healthy volunteers to assess safety, pharmacokinetics, and transient biomarker changes by the ABCA1 agonist CS6253
在男性和女性健康志愿者中进行的一项随机双盲安慰剂对照 1 期 SAD 研究,旨在评估 ABCA1 激动剂 CS6253 的安全性、药代动力学和短暂生物标志物变化
  • 批准号:
    10734158
  • 财政年份:
    2023
  • 资助金额:
    $ 38.63万
  • 项目类别:
Investigating mechanisms underpinning outcomes in people on opioid agonist treatment for OUD: Disentangling sleep and circadian rhythm influences on craving and emotion regulation
研究阿片类激动剂治疗 OUD 患者结果的机制:解开睡眠和昼夜节律对渴望和情绪调节的影响
  • 批准号:
    10784209
  • 财政年份:
    2023
  • 资助金额:
    $ 38.63万
  • 项目类别:
A novel nanobody-based agonist-redirected checkpoint (ARC) molecule, aPD1-Fc-OX40L, for cancer immunotherapy
一种基于纳米抗体的新型激动剂重定向检查点 (ARC) 分子 aPD1-Fc-OX40L,用于癌症免疫治疗
  • 批准号:
    10580259
  • 财政年份:
    2023
  • 资助金额:
    $ 38.63万
  • 项目类别:
Identification and characterization of a plant growth promoter from wild plants: is this a novel plant hormone agonist?
野生植物中植物生长促进剂的鉴定和表征:这是一种新型植物激素激动剂吗?
  • 批准号:
    23K05057
  • 财政年份:
    2023
  • 资助金额:
    $ 38.63万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了