Glucocorticoid Receptors (GR) in Mitochondria: The Role

糖皮质激素受体 (GR) 在线粒体中的作用

基本信息

项目摘要

Chronic stress has been shown to be associated clinically with formation of depression in patients and hormones are known to mediate certain clinical manifestations of mood disorders. Chronic restraint stress induces a morphological reorganization in the areas of rodent brain, effects which are also accompanied by behavioral changes. Although the precise mechanisms underlying these effects remain to be elucidated, increasing data suggests that an alteration in neuroprotection and mitochondrial functions may play an important role in regulating various forms of synaptic and neural plasticity; we have sought to investigate the mitochondrial functions regulated by hormones during chronic stress. Cortical neuronal cultures were established in order to determine the localization and function of glucocorticoid receptors in the mitochondria. Glucocorticoid receptors translocated into mitochondria after 1.5 hour treatment with low concentration (100 nM) and high concentration (1,000 nM) of corticosterone in cultured cortical neurons. Consistent with the enhancement of mitochondrial function, mitochondrially encoded gene cytochrome oxidase I (COXI) (has GRE in its promoter region) expression was also increased in mitochondria fraction after 24 hours treatment. However, after three days of treatment, 1uM corticosterone resulted in a decrease in GR levels in mitochondria and 100nM corticosterone treatment did not. Similarly, mitochondrial membrane potential were enhanced after one day treatment with high (1uM) and low (100nM) concentration of corticosterone in a similar extend, and only high concentration (1uM) significantly decreased in mitochondrial membrane potential after 3 day treatment in comparison to the 100nM corticosterone. In addition, mitochondrial oxidation were enhanced after one day treatment with high (1uM) and low (100nM) concentration of corticosterone in a similar extend, and only high concentration (1uM) significantly decreased in mitochondrial membrane potential after 3 day treatment in comparison to the 100nM corticosterone and untreated control. To determine the situation under chronic stress, we found that glucocorticoid receptor levels in mitochondria were significantly decreased in the mitochondrial fraction from prefrontal cortex tissue after chronic stress, suggesting a similar change after high concentration and long-term corticosterone treatment in vitro. These studies may provide additional insights into the mechanisms by which glucocorticoid regulate mitochondrial function and neuronal signaling. Furthermore, this research also has the potential to contribute to a more complete understanding of the mechanisms by which chronic stress and hormones regulate cellular plasticity and resilience and to the future development of improved therapeutics.
慢性压力在临床上与患者抑郁症的形成有关,并且已知激素介导情绪障碍的某些临床表现。慢性束缚应激诱导啮齿类动物大脑区域的形态重组,其影响也伴随着行为变化。虽然这些影响的确切机制仍有待阐明,但越来越多的数据表明,神经保护和线粒体功能的改变可能在调节各种形式的突触和神经可塑性方面发挥重要作用;我们试图研究慢性应激期间激素调节的线粒体功能。 建立皮质神经元培养物以确定线粒体中糖皮质激素受体的定位和功能。在培养的皮质神经元中,用低浓度(100 nM)和高浓度(1,000 nM)皮质酮处理1.5小时后,糖皮质激素受体易位到线粒体中。与线粒体功能的增强一致,在处理24小时后,线粒体部分中的线粒体编码基因细胞色素氧化酶I(COXI)(在其启动子区具有GRE)表达也增加。然而,在处理三天后,1 μ M皮质酮导致线粒体中GR水平降低,而100 nM皮质酮处理则没有。同样,高浓度(1 μ M)和低浓度(100 nM)皮质酮处理1天后,线粒体膜电位以相似程度增强,与100 nM皮质酮相比,仅高浓度(1 μ M)处理3天后线粒体膜电位显著降低。此外,高浓度(1 μ M)和低浓度(100 nM)皮质酮处理1天后,线粒体氧化增强程度相似,与100 nM皮质酮和未处理对照相比,仅高浓度(1 μ M)处理3天后线粒体膜电位显著降低。为了确定在慢性应激下的情况,我们发现,糖皮质激素受体水平在线粒体中显着下降,在线粒体组分从前额叶皮层组织慢性应激后,表明类似的变化后,高浓度和长期的皮质酮在体外治疗。这些研究可能为糖皮质激素调节线粒体功能和神经元信号传导的机制提供额外的见解。此外,这项研究也有可能有助于更全面地了解慢性应激和激素调节细胞可塑性和弹性的机制,以及未来改进治疗方法的发展。

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 }}

HUSSEINI K MANJI其他文献

HUSSEINI K MANJI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('HUSSEINI K MANJI', 18)}}的其他基金

LITHIUM RESPONSIVE BIPOLAR DISORDER AND CNS MYO INOSITOL
锂反应性双相情感障碍和中枢神经系统肌醇
  • 批准号:
    2908653
  • 财政年份:
    1999
  • 资助金额:
    --
  • 项目类别:
PKC SIGNALING AND THE TREATMENT OF BIPOLAR DISORDER
PKC 信号传导和双相情感障碍的治疗
  • 批准号:
    2702902
  • 财政年份:
    1998
  • 资助金额:
    --
  • 项目类别:
PKC SIGNALING AND THE TREATMENT OF BIPOLAR DISORDER
PKC 信号传导和双相情感障碍的治疗
  • 批准号:
    2891036
  • 财政年份:
    1998
  • 资助金额:
    --
  • 项目类别:
Microarray Studies -- Long Term Treatment for Bipolar
微阵列研究——双相情感障碍的长期治疗
  • 批准号:
    6824378
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Antidepressant Efficacy of Antiglutamatergic Agent
抗谷氨酸药的抗抑郁功效
  • 批准号:
    6824387
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Neuronal-Glial Interaction in the Treatment of Bipolar
双相情感障碍治疗中的神经元-胶质细胞相互作用
  • 批准号:
    6824400
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Antidepressant Efficacy of an Antiglutamatergic Agent in
抗谷氨酸药物的抗抑郁功效
  • 批准号:
    7312904
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Roles of kainate receptors in behavioral plasticity rela
红藻氨酸受体在行为可塑性关系中的作用
  • 批准号:
    7312942
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
Felbamate for Treatment-Resistant Bipolar Depression
非氨酯治疗难治性双相抑郁症
  • 批准号:
    6982741
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
The Protein Kinase C Inhibitor Tamoxifen in Acute Mania
蛋白激酶 C 抑制剂他莫昔芬治疗急性躁狂症
  • 批准号:
    6982748
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:

相似国自然基金

BMP9/BMP type I receptors 通过激活 PPARα保护心肌梗死的机制研究
  • 批准号:
    LQ22H020003
  • 批准年份:
    2021
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
Oleamide 对神经细胞钠离子通道(VSSCs)及GABAa Receptors
  • 批准号:
    30240004
  • 批准年份:
    2002
  • 资助金额:
    7.0 万元
  • 项目类别:
    专项基金项目

相似海外基金

Adaptive Artificial Receptors for Biomimetic Functions
仿生功能的自适应人工受体
  • 批准号:
    MR/X023303/1
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Fellowship
Conference: 2024 Photosensory Receptors and Signal Transduction GRC/GRS: Light-Dependent Molecular Mechanism, Cellular Response and Organismal Behavior
会议:2024光敏受体和信号转导GRC/GRS:光依赖性分子机制、细胞反应和生物体行为
  • 批准号:
    2402252
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Standard Grant
Intelligent cryo-electron microscopy of G protein-coupled receptors
G 蛋白偶联受体的智能冷冻电子显微镜
  • 批准号:
    23K23818
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Atypical Chemokine Receptors orchestrate changes in vascular patterning during fibrotic liver disease via Endothelial-to-Mesenchymal Transition.
非典型趋化因子受体通过内皮-间质转化协调纤维化肝病期间血管模式的变化。
  • 批准号:
    MR/Y013751/1
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Research Grant
Conformations of musk odorants and their binding to human musk receptors
麝香气味剂的构象及其与人类麝香受体的结合
  • 批准号:
    EP/X039420/1
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Research Grant
Structural studies into human muscle nicotinic acetylcholine receptors
人体肌肉烟碱乙酰胆碱受体的结构研究
  • 批准号:
    MR/Y012623/1
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Research Grant
Innovative ligands for nuclear receptors to eradicate cancer relapse
核受体的创新配体可根除癌症复发
  • 批准号:
    EP/Y030818/1
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Research Grant
Molecular insights into the allosteric regulation of opioid receptors
阿片受体变构调节的分子见解
  • 批准号:
    DE240100931
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Discovery Early Career Researcher Award
Self RNA sensing by cytosolic innate immune receptors
胞质先天免疫受体的自身 RNA 传感
  • 批准号:
    MR/Y013212/1
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Research Grant
Exploration of T- and B-cell receptors to eliminate the foreign body reaction from synthetic polymeric scaffolds
探索 T 细胞和 B 细胞受体以消除合成聚合物支架的异物反应
  • 批准号:
    24K19917
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了