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

• 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
• 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

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.

家长资助：“控制星形胶质细胞的发展和星形胶质细胞-突触相互作用” （1R01NS102237-01A1） 标题：“通过神经胶质素-神经肽相互作用调节星形胶质细胞和突触发育” 神经胶质素已被证明在突触前和突触后元件的神经元组织中起关键作用， 通过突触与它们的伴侣神经毒素联系。有三个神经配蛋白家族成员（NL 1， NL 2和NL 3）。在神经元突触处，这些细胞粘附分子已被证明增加了神经元的粘附。 突触数量以及功能上改变突触传递。神经胶质素和神经毒素也具有 与自闭症和精神分裂症等疾病的风险有关。我们实验室最近的研究表明 星形胶质细胞（大脑的主要胶质细胞亚型）也表达神经胶质素。我们的实验室证明， 星形胶质细胞神经胶质蛋白是星形胶质细胞正常形态发生所必需的，并且该过程依赖于 神经毒素星形胶质细胞中NL 2的缺失改变了突触的正常发育，表明 星形胶质细胞形态和突触功能之间的联系我们的目标是了解 星形胶质细胞与潜在的突触回路一起获得它们的形态。具体来说，我们将 研究另外两种神经配素（NL 1和NL 3）介导星形胶质细胞之间联系的机制。 和突触发育。通过这些研究，我们将讨论星形胶质细胞在脑缺血中的重要作用。 神经发育障碍的病因学，如自闭症，其中突触病理学是潜在的驱动因素 疾病的表型。此外，我们将加深我们对细胞间相互作用的机械理解， 控制大脑的发育和功能。 这项研究将在杜克大学进行，由Cagla Eroglu博士和Ji Ru-Rong博士指导。 杜克大学是一所领先的研究机构，在细胞生物学研究生培训方面有着出色的记录， 神经生物学除了获得一流的核心设施，包括转基因小鼠，光学显微镜和 在蛋白质组学方面，具有神经胶质和突触专业知识的实验室之间有着强大的合作文化 生物学，这将有助于培训和候选人拉米雷斯先生的成功。埃罗格鲁博士是一位 在神经胶质细胞和神经元细胞生物学方面， 交互. Ji博士在慢性疼痛的神经胶质相互作用领域享有盛誉，特别擅长于 电生理学他们的指导将共同确保成功实施这一战略所需的连贯一致的培训。 项目