Neuron-satellite glia interactions in the sympathetic nervous system
交感神经系统中神经元-卫星胶质细胞的相互作用
基本信息
- 批准号:10719545
- 负责人:
- 金额:$ 56.69万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-07-01 至 2028-06-30
- 项目状态:未结题
- 来源:
- 关键词:AblationAddressAdhesivesAxonBAX geneBiochemicalBiochemistryBrainCandidate Disease GeneCell CommunicationCell physiologyCell-Cell AdhesionCellular MorphologyCellular biologyCoculture TechniquesCommunicationCongestive Heart FailureCuesDefectDendritesDependenceDevelopmentDiabetes MellitusDiseaseEGF geneEnvironmentFunctional disorderGangliaGeneticGlial Cell ProliferationGoalsGrowthHeart failureHomeostasisHumanHypertensionImageIn VitroIndividualInsulin ResistanceIntegral Membrane ProteinKnockout MiceKnowledgeLinkMediatingMembrane ProteinsModelingMolecularMorphogenesisMorphologyMusMutant Strains MiceNGFR ProteinNerve RegenerationNervous SystemNeurogliaNeuronsNeurotrophic Tyrosine Kinase Receptor Type 1OrganOutputParkinson DiseasePathway interactionsPeripheralPeripheral Nervous System DiseasesPhysiologyProcessReportingResearchRoleSignal TransductionStructureSympathetic GangliaSympathetic Nervous SystemSynapsesSynaptic TransmissionSystemTestingTissuesWorkcell typechronic painconditional knockoutdefined contributionfightingglial cell developmentin vivomouse geneticsmouse modelnerve supplyneural circuitneuron developmentneuron lossneuronal cell bodyneuronal survivalneurotrophic factornotch proteinpreventreceptorreceptor bindingresponsesatellite cellsingle cell sequencingsingle-cell RNA sequencing
项目摘要
The sympathetic nervous system is a key regulator of whole body physiology. A
dysfunctional sympathetic nervous system is linked to a growing list of human disorders
including chronic heart failure, hypertension, and insulin resistance. Despite decades of
research on sympathetic neurons, satellite glia, the major glial cells in sympathetic ganglia,
have remained an enigmatic component of the system. Satellite glia tightly ensheathe
sympathetic neuron cell bodies. In recent work, we revealed a role for satellite glial cells
in restricting neuron activity to thereby modulate sympathetic output to peripheral organs.
Our findings suggest that sympathetic neurons and their surrounding satellite glia should
be considered as structural and functional units that orchestrate the formation and
functioning of the sympathetic nervous system. However, satellite glia are a vastly under-
studied cell type in the nervous system, with limited understanding of their development,
neuron-glia communication, and how they contribute to neural circuits.
This application addresses this knowledge gap by seeking to define how
sympathetic neuron-satellite glia units are established during development, and how
perturbations in this process impact neuronal connectivity and function. Based on our
preliminary results, we hypothesize that target-derived neurotrophin signaling in
sympathetic neurons instructs contact-based interactions with neighboring satellite glia
during development. The goal of this application is to test this hypothesis and define the
molecular underpinnings of this bi-directional neuron-satellite glia interactions using
genetic mouse models, neuron-glia co-cultures, biochemistry, and imaging. Our studies
will establish a fundamental knowledge of how these poorly studied glial cells contribute
to nervous system connectivity and function and will inform new strategies for treating
disorders linked to sympathetic dysfunction.
交感神经系统是全身生理的关键调节器。一
交感神经系统功能失调与越来越多的人类疾病有关
包括慢性心力衰竭、高血压和胰岛素抵抗。尽管经过数十年的
研究交感神经元,卫星胶质细胞,交感神经节中的主要胶质细胞,
一直是这个系统中神秘的一部分卫星胶质细胞紧紧包裹
交感神经元细胞体。在最近的工作中,我们揭示了卫星神经胶质细胞的作用,
限制神经元活动,从而调节到外周器官的交感神经输出。
我们的研究结果表明,交感神经元及其周围的卫星胶质细胞应该
被认为是协调形成的结构和功能单元,
交感神经系统的功能。然而,卫星神经胶质细胞是一个大大低于-
研究神经系统中的细胞类型,对它们的发育了解有限,
神经元-神经胶质细胞通讯,以及它们如何对神经回路做出贡献。
该应用程序通过寻求定义如何解决这一知识差距
交感神经元卫星神经胶质细胞单位是在发育过程中建立的,以及如何
该过程中的扰动影响神经元连接和功能。基于我们
初步结果,我们假设,靶源性神经营养因子信号转导,
交感神经元指导与邻近卫星胶质细胞的接触式相互作用
在发展过程中。本应用程序的目标是测试此假设并定义
这种双向神经元-卫星神经胶质相互作用的分子基础,
遗传小鼠模型、神经元-胶质细胞共培养、生物化学和成像。我们的研究
将建立一个基本的知识,这些缺乏研究的神经胶质细胞如何贡献
神经系统的连接和功能,并将为治疗
与交感神经功能障碍有关的疾病
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)
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Rejji Kuruvilla其他文献
Rejji Kuruvilla的其他文献
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{{ truncateString('Rejji Kuruvilla', 18)}}的其他基金
2023 Neurotrophic Mechanisms in Health and Disease
2023 健康与疾病中的神经营养机制
- 批准号:
10654336 - 财政年份:2023
- 资助金额:
$ 56.69万 - 项目类别:
Coupled axonal protein synthesis and lipidation in axon growth and homeostasis
轴突生长和稳态中的耦合轴突蛋白合成和脂化
- 批准号:
10318573 - 财政年份:2019
- 资助金额:
$ 56.69万 - 项目类别:
Neurotrophic factor trafficking and signaling in development and disease
发育和疾病中的神经营养因子运输和信号传导
- 批准号:
9897598 - 财政年份:2019
- 资助金额:
$ 56.69万 - 项目类别:
2019 Neurotrophic Mechanisms in Health and Disease Gordon Research Conference
2019年健康与疾病中的神经营养机制戈登研究会议
- 批准号:
9755039 - 财政年份:2019
- 资助金额:
$ 56.69万 - 项目类别:
Coupled axonal protein synthesis and lipidation in axon growth and homeostasis
轴突生长和稳态中的耦合轴突蛋白合成和脂化
- 批准号:
10056229 - 财政年份:2019
- 资助金额:
$ 56.69万 - 项目类别:
Neurotrophic factor trafficking and signaling in development and disease
发育和疾病中的神经营养因子运输和信号传导
- 批准号:
10377384 - 财政年份:2019
- 资助金额:
$ 56.69万 - 项目类别:
Coupled axonal protein synthesis and lipidation in axon growth and homeostasis
轴突生长和稳态中的耦合轴突蛋白合成和脂化
- 批准号:
10534132 - 财政年份:2019
- 资助金额:
$ 56.69万 - 项目类别:
Sympathetic innervation in pancreatic development and function
胰腺发育和功能中的交感神经支配
- 批准号:
8751267 - 财政年份:2014
- 资助金额:
$ 56.69万 - 项目类别:
Sympathetic innervation in pancreatic development and function
胰腺发育和功能中的交感神经支配
- 批准号:
8890854 - 财政年份:2014
- 资助金额:
$ 56.69万 - 项目类别:
Neurotrophin mechanisms in neural development and disease
神经营养蛋白在神经发育和疾病中的机制
- 批准号:
8322573 - 财政年份:2011
- 资助金额:
$ 56.69万 - 项目类别:
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