Control of Astrocyte Development and Astrocyte-Synapse Interactions

星形胶质细胞发育和星形胶质细胞突触相互作用的控制

基本信息

批准号：
9930268
负责人：
Cagla Eroglu
金额：
$ 4.5万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9930268
关键词：
Actins Address Affect Animals Astrocytes Biology Biotin Brain C-terminal Cell Adhesion Molecules Cell Communication Cell physiology Cells Cellular biology Complex Core Facility Cytoskeleton Data Development Disease Disease Outcome Electrophysiology (science)Electroporation Elements Ensure Etiology Excitatory Synapse Family member Functional disorder Future GLAST Protein Goals Homeostasis Human Immunohistochemistry Impairment Investigation Ions Label Lead Life Ligase Link LoxP-flanked allele Mediating Mentorship Methods Morphogenesis Morphology Mus National Research Service Awards Neuraxis Neurobiology Neurodegenerative Disorders Neurodevelopmental Disorder Neuroglia Neurons Neurotransmitters Pathogenesis Pathology Pathway interactions Play Process Proteins Proteome Proteomics Publications Records Recycling Regulation Research Research Institute Resistance Role Schizophrenia Signal Pathway Signal Transduction Structure Synapses Synaptic Transmission Testing Time Training Transgenic Mice Universities Vertebral column Vision Visual Cortex Work autism spectrum disorder chronic pain cohesion dark rearing disease phenotype disorder risk experience experimental study extracellular graduate student in vivo insight knock-down light microscopy mind control neural circuit neuroligin 1 neuroligin 3 neuropathology new therapeutic target notch protein novel parent grant postnatal postsynaptic response small hairpin RNA success synaptic function synaptogenesis

项目摘要

Parent Grant: “Control of Astrocyte Development and Astrocyte-Synapse Interactions” (1R01NS102237-01A1) Title: "Regulation of Astrocyte and Synapse Development via Neuroligin-Neurexin Interactions" Neuroligins have been shown to play key roles in neuronal organization of pre- and postsynaptic elements by associating transsynaptically with their partners, the neurexins. There are three neuroligin family members (NL1, NL2 and NL3). At the neuronal synapse, these cell adhesion molecules have been shown to increase the number of synapses as well as functionally alter synaptic transmission. Neuroligins and neurexins have also been implicated in the risk for disorders such as autism and schizophrenia. Recent work from our lab has shown that astrocytes, the primary glial subtype of the brain, express neuroligins as well. Our lab demonstrated that astrocyte neuroligins are required for proper astrocyte morphogenesis and that this process is dependent on neuronal neurexins. The loss of NL2 in astrocytes altered the proper development of synapses indicating a link between proper astrocyte morphology and synapse function. Our goal is to understand the mechanism by which astrocytes attain their morphology in conjunction with the underlying synaptic circuitry. Specifically, we will investigate the mechanisms by which the two other neuroligins (NL1 and NL3) mediate the link between astrocyte and synapse development. Through these studies, we will address the important roles astrocytes play in the etiology of neurodevelopmental disorders, such as autism, in which synaptic pathology is the underlying driver of disease phenotypes. Moreover, we will deepen our mechanistic understanding of cell-cell interactions that control brain development and function. This research will take place at Duke University, under the mentorship of Dr. Cagla Eroglu and Dr. Ji Ru-Rong. Duke University is a leading research institute, with stellar records in graduate training in cell biology and neurobiology. Apart from access to top notch core facilities including transgenic mice, light microscopy and proteomics, there is a strong collaborative culture between the labs that have expertise in glia and synapse biology, which will contribute to the training and success of the candidate Mr. Ramirez. Dr. Eroglu is an expert in glial and neuronal cell biology who is well-established in the fields of synapse formation and neuron-glia interactions. Dr. Ji is renowned in the field of neuro-glia interactions in chronic pain with a particular expertise in electrophysiology. Together, their mentorship will ensure cohesive training required for the success of this project.

父母赠款：“控制星形胶质细胞发展和星形胶质细胞 - 伴侣相互作用” （1R01NS102237-01A1）标题：“通过神经素系素相互作用对星形胶质细胞和突触发展的调节” 已证明神经素在前和突触后元素的神经元组织中起关键作用与他们的伴侣神经毒素相关联。有三个神经素家庭成员（NL1， NL2和NL3）。在神经元突触，这些细胞粘附分子已被证明增加了突触的数量以及功能改变突触传递。神经素和神经毒素也具有我们与自闭症和精神分裂症等疾病的风险有关。我们实验室的最新工作已显示星形胶质细胞是大脑的主要神经胶质亚型，也表达神经素。我们的实验室证明了星形胶质细胞神经素需要适当的星形胶质细胞形态发生，并且此过程取决于神经元神经毒素。星形胶质细胞中NL2的损失改变了突触的正确发展，表明有联系在适当的星形胶质形态和突触功能之间。我们的目标是了解该机制星形胶质细胞与潜在的突触回路结合使用。具体来说，我们会的研究其他两个神经素（NL1和NL3）介导星形胶质细胞之间的联系的机制和突触发展。通过这些研究，我们将解决星形胶质细胞在神经发育障碍（例如自闭症）的病因，其中突触病理是基础驱动力疾病表型。此外，我们将加深对细胞 - 细胞相互作用的机械理解控制脑发育和功能。这项研究将在Cagla Eroglu博士和Ji Ru-Rong博士的心态下在杜克大学进行。杜克大学是一家领先的研究所，拥有细胞生物学研究生培训的出色记录和神经生物学。除了进入一流的核心设施，包括转基因小鼠，光学显微镜和蛋白质组学，实验室之间具有强烈的协作文化，在神经胶质和突触方面具有专业知识生物学将有助于候选人拉米雷斯先生的培训和成功。 Eroglu博士是专家在神经元和神经元细胞生物学中，在突触形成和神经元格里亚领域已建立了良好互动。 Ji博士在慢性疼痛中的神经胶质相互作用领域以特殊的专业知识而闻名电生理学。他们的精神训练将确保成功所需的凝聚力培训项目。