The role of aldosterone in mediating depressive-like behavior in a rat model of heart failure

醛固酮在介导心力衰竭大鼠模型抑郁样行为中的作用

基本信息

  • 批准号:
    9171478
  • 负责人:
  • 金额:
    $ 29.15万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-08-15 至 2020-08-14
  • 项目状态:
    已结题

项目摘要

Project Summary Congestive heart failure (CHF) and mood disorders occur as comorbid conditions at an alarmingly high rate. The incidence of depression in patients that have survived a myocardial infarction (MI) has been reported to be as high as 45%, while occurring at a rate of 2-9% in the general population. Post-MI patients that develop depression are at a much greater risk of experiencing an adverse cardiovascular event within one year as compared to non-depressed patients. In spite of the profound clinical relevance, the mechanisms that promote depression in CHF patients are not known. A compelling hypothesis regarding the coincidence of cardiovascular disease and depression is that the etiological mechanisms in both disorders are similar. Among the commonly observed physiological maladaptations, high circulating levels of the adrenal mineralocorticoid hormone aldosterone (ALDO) have been reported in animal models and human clinical cases of major depressive disorder and CHF. The current proposal will explore the role of ALDO in promoting affective and cognitive impairments in a rat model of CHF that recapitulates many of the physiological outcomes observed in human patients. CHF is induced by coronary artery ligation to induce MI, the most frequent cause of CHF in humans. The neurological impact of CHF is then studied using behavioral and electrophysiological methods. Specifically, we will measure anhedonia, a core symptom of major depressive disorder in humans, as well as cognitive function which is frequently impaired in CHF patients and in individuals with major depressive disorder. The ability of central treatments with mineralocorticoid receptor antagonists to prevent depressive- like behavior and learning and memory deficits will be determined. Synaptic function in the hippocampus, a brain region implicated in mood disorders and cognitive function, is assessed in animals with CHF using electrophysiological techniques. Finally, we will investigate the neurotrophin brain-derived neurotrophic factor (BDNF) as a potential downstream mediator of the behavioral effects of high circulating ALDO in CHF. BDNF expression in the hippocampus has been implicated in mood and cognition and neurological responses to physiological and psychological stressors. The efficacy of direct infusion of BDNF into the hippocampus in preventing aberrant behavioral phenotypes in CHF will be tested, as well as the efficacy of exercise, a behavioral manipulation known to have positive effects on mood, cognition, and cardiac function, and robustly enhance BDNF expression. Results generated from this proposal will enhance our understanding of the impact of cardiac disease states on the brain as well as suggest potential therapeutic avenues for reducing the deleterious impact of CHF on quality of life.
项目摘要 充血性心力衰竭(CHF)和情绪障碍作为共病疾病以惊人的高发生率发生。 据报道,心肌梗死(MI)患者的抑郁症发病率是 高达45%,而在一般人群中发生率为2-9%。发生心肌梗死后患者 抑郁症患者在一年内发生不良心血管事件的风险要大得多, 与非抑郁症患者相比。尽管具有深刻的临床意义,但促进 尚不清楚CHF患者的抑郁症。一个令人信服的假设, 心血管疾病和抑郁症的共同点在于,两种疾病的病因机制相似。之间 常见的生理适应不良,肾上腺盐皮质激素的高循环水平 激素醛固酮(ALDO)已在动物模型和人类临床病例中报道, 抑郁症和CHF。目前的建议将探讨ALDO在促进情感和 CHF大鼠模型中的认知障碍,该模型概括了在以下研究中观察到的许多生理结果: 人类病人CHF是通过冠状动脉结扎诱导MI而诱导的,MI是CHF的最常见原因, 人类然后使用行为和电生理学方法研究CHF的神经影响。 具体来说,我们将测量快感缺失,人类重度抑郁症的核心症状,以及 CHF患者和重度抑郁症患者的认知功能经常受损 disorder.使用盐皮质激素受体拮抗剂的中心治疗预防抑郁症的能力- 比如行为和学习记忆缺陷。海马体中的突触功能, 使用以下方法评估CHF动物中与情绪障碍和认知功能有关的大脑区域 电生理技术。最后,我们将探讨神经营养素脑源性神经营养因子 脑源性神经营养因子(BDNF)作为CHF中高循环ALDO行为效应的潜在下游介质。BDNF 在海马中的表达与情绪、认知和神经反应有关, 生理和心理压力源。脑源性神经营养因子(BDNF)直接注入海马的疗效观察 将测试预防CHF中异常行为表型的作用,以及运动的功效, 已知行为操纵对情绪、认知和心脏功能有积极影响, 增强BDNF表达。这项建议所产生的结果将加强我们对 心脏病状态对大脑的影响,并提出了减少心脏病的潜在治疗途径。 CHF对生活质量的有害影响。

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 }}

Michael John Morris其他文献

Michael John Morris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 }}

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 29.15万
  • 项目类别:
    Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 29.15万
  • 项目类别:
    Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 29.15万
  • 项目类别:
    Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 29.15万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 29.15万
  • 项目类别:
    Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 29.15万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 29.15万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 29.15万
  • 项目类别:
    EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 29.15万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 29.15万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了