The Role of CHD7 in ACC neurons
CHD7 在 ACC 神经元中的作用
基本信息
- 批准号:10511885
- 负责人:
- 金额:$ 68.99万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-07 至 2027-07-31
- 项目状态:未结题
- 来源:
- 关键词:AdultAffectAnteriorAnxietyAxonBehaviorBehavioralBinding SitesBrainCHD7 geneCell NucleusChIP-seqChromatinChromatin Remodeling FactorComplexDataDevelopmentEmbryoEpigenetic ProcessExcitatory SynapseExposure toFemaleGTP-Binding Protein alpha Subunits, GsGTP-Binding ProteinsGene ExpressionGene Expression RegulationGenetic TranscriptionGoalsHumanIndividualKnowledgeLightMapsMedialMental HealthMental disordersMolecularMolecular ProfilingMoodsMusNeuronsNuclearPathway interactionsPlayPrefrontal CortexProcessPropertyRegulationResearchRodentRoleSamplingSignal TransductionSignaling MoleculeSignaling ProteinStressStructure of terminal stria nuclei of preoptic regionSynapsesTestingWild Type Mouseanxiety-related behaviorbasebehavioral responsebiological adaptation to stresscingulate cortexclinical applicationemotional behaviorenvironmental stressorepigenetic regulationepigenomeepigenomicsexcitatory neuronexperiencegene networkimprovedmalemultiple omicsneurodevelopmentneuronal circuitryneurophysiologynovelresponsesexual dimorphismtranscriptome
项目摘要
A limited fundamental understanding of the cellular and molecular mechanisms underlying complex behaviors
poses a major barrier for development of effective clinical applications to treat mental disorders. The long-term
goal of our research is to shed light on the gaps in knowledge regarding the molecular signatures and synaptic
properties of brain neuronal circuits that control responses to stress. Epigenetic gene regulation has emerged
as a key molecular driver underlying neuronal circuit dynamics and behavioral changes. Our preliminary data
suggest that CHD7, a chromatin-remodeling factor primarily expressed in the embryonic brain, remains enriched
in excitatory neurons within layer 2/3 of the anterior cingulate cortex (ACC) in adult mice. The ACC, a region
within the medial prefrontal cortex in rodents, plays critical roles in processing mood-related information and
modulating anxiety-related behaviors. While critical roles for CHD7 during neural development have been well-
documented, its function in postmitotic neurons remains unclear. Our data suggest that postmitotic deletion of
Chd7 from ACC excitatory neurons (referred to as Chd7cKO) significantly reduced innate anxiety levels. In
addition, neuronal activity in the ACC of Chd7cKO mice exposed to an environmental stressor was significantly
lower than that in wild type (WT) mice. Intriguingly, these phenomena were observed only in male (and not
female) mice, indicating sexual dimorphism of CHD7 function. Our data provide the first evidence suggesting an
essential role for CHD7 in postmitotic ACC neurons in regulating neuronal activity and innate anxiety. Our primary
objectives are to interrogate the role of CHD7 in controlling a complex gene network to regulate the synaptic
activity of ACC neurons and their downstream targets. In this proposal, we will first determine how CHD7
regulates the activity of ACC neurons and their downstream targets in the bed nucleus of the stria terminalis
(BNST). Our preliminary data suggest that CHD7 plays a critical role in maintaining proper neuronal activity in
the ACC-BNST pathway. Next, we will use unbiased high-throughput approaches to determine how CHD7
controls a complex gene network in postmitotic neurons to regulate activity-dependent gene transcription. Finally,
we will investigate how CHD7 activity is regulated by an interacting partner that is involved in G protein signaling.
If successful, our research will shed new light on the molecular underpinnings and neurophysiology of neuronal
circuits that respond to stress. Such information will ultimately help define mechanisms underlying complex
emotional behaviors in humans.
对复杂行为背后的细胞和分子机制的基本理解有限
对开发治疗精神障碍的有效临床应用构成了主要障碍。长期
我们研究的目标是揭示关于分子特征和突触的知识差距,
控制对压力反应的大脑神经元回路的特性。表观遗传基因调控已经出现
作为神经元回路动力学和行为变化的关键分子驱动器。我们的初步数据
提示主要在胚胎脑中表达的染色质重塑因子CHD 7仍然富集
在成年小鼠前扣带皮层(ACC)2/3层内的兴奋性神经元中。ACC,一个区域
在啮齿类动物的内侧前额叶皮层中,在处理与情绪有关的信息方面起着关键作用,
调节焦虑相关的行为虽然CHD 7在神经发育过程中的关键作用已经很好-
有文献记载,其在有丝分裂后神经元中的功能仍不清楚。我们的数据表明,有丝分裂后缺失的
来自ACC兴奋性神经元的Chd 7(称为Chd 7 cKO)显著降低先天性焦虑水平。在
此外,暴露于环境应激物的Chd 7 cKO小鼠的ACC中的神经元活性显著降低。
低于野生型(WT)小鼠。有趣的是,这些现象只在男性中观察到(而不是在男性中观察到)。
雌性)小鼠,表明CHD 7功能的两性异形。我们的数据提供了第一个证据,表明
CHD 7在有丝分裂后ACC神经元中调节神经元活性和先天性焦虑中的重要作用。我们的首要
目的是询问CHD 7在控制复杂基因网络以调节突触中的作用。
ACC神经元及其下游靶点的活性。在这个建议中,我们将首先确定CHD 7如何
调节终纹床核中ACC神经元及其下游靶点的活性
(BNST).我们的初步数据表明,CHD 7在维持正常的神经元活动中起着关键作用。
ACC-BNST通路。接下来,我们将使用无偏的高通量方法来确定CHD 7
控制有丝分裂后神经元中的复杂基因网络以调节活性依赖性基因转录。最后,
我们将研究CHD 7的活性是如何通过参与G蛋白信号传导的相互作用伴侣来调节的。
如果成功,我们的研究将为神经元的分子基础和神经生理学提供新的线索
对压力做出反应的电路。这些信息最终将有助于确定复杂的
人类的情感行为。
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 }}
KAI JIAO其他文献
KAI JIAO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('KAI JIAO', 18)}}的其他基金
SEMA6D-mediated breast cancer disparity, metastasis, and tumor-immune interaction
SEMA6D 介导的乳腺癌差异、转移和肿瘤免疫相互作用
- 批准号:
10634959 - 财政年份:2023
- 资助金额:
$ 68.99万 - 项目类别:
Critical roles of CHD7 during mouse cardiogenesis
CHD7 在小鼠心脏发生过程中的关键作用
- 批准号:
10625572 - 财政年份:2022
- 资助金额:
$ 68.99万 - 项目类别:
Test the role of cardiac expressed SEMA6D in Alzheimer's disease
测试心脏表达的 SEMA6D 在阿尔茨海默病中的作用
- 批准号:
9814376 - 财政年份:2019
- 资助金额:
$ 68.99万 - 项目类别:
Roles of Semaphorin Signaling in Breast Cancer Racial Disparities
信号蛋白信号传导在乳腺癌种族差异中的作用
- 批准号:
8972564 - 财政年份:2015
- 资助金额:
$ 68.99万 - 项目类别:
Roles of Semaphorin Signaling in Breast Cancer Racial Disparities
信号蛋白信号传导在乳腺癌种族差异中的作用
- 批准号:
9110916 - 财政年份:2015
- 资助金额:
$ 68.99万 - 项目类别:
Molecular mechanisms regulating mouse valvulogenesis
调节小鼠瓣膜发生的分子机制
- 批准号:
8931798 - 财政年份:2014
- 资助金额:
$ 68.99万 - 项目类别:
Molecular mechanisms regulating mouse valvulogenesis
调节小鼠瓣膜发生的分子机制
- 批准号:
8808087 - 财政年份:2014
- 资助金额:
$ 68.99万 - 项目类别:
Critical roles of CHD7 during mouse cardiogenesis
CHD7 在小鼠心脏发生过程中的关键作用
- 批准号:
10162637 - 财政年份:2010
- 资助金额:
$ 68.99万 - 项目类别:
相似海外基金
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 68.99万 - 项目类别:
Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 68.99万 - 项目类别:
Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 68.99万 - 项目类别:
Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 68.99万 - 项目类别:
Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 68.99万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 68.99万 - 项目类别:
Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 68.99万 - 项目类别:
Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 68.99万 - 项目类别:
Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
- 批准号:
23K00129 - 财政年份:2023
- 资助金额:
$ 68.99万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
- 批准号:
2883985 - 财政年份:2023
- 资助金额:
$ 68.99万 - 项目类别:
Studentship