The role of astrocytes in inhibitory synaptogenesis

星形胶质细胞在抑制性突触发生中的作用

• 批准号: 7661597
• 负责人: Ethan Garrett Hughes
• 金额: $ 0.42万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7661597
• 关键词: Affect; Astrocytes; Autistic Disorder; Axon; Biological Assay; Cholesterol; Coculture Techniques; Complex; Conditioned Culture Media; Confocal Microscopy; Data; Development; Disease; Embryo; Epilepsy; Excitatory Synapse; Fibroblasts; Fluorescence-Activated Cell Sorting; Foundations; Fractionation; Future; Goals; Heating; Heparin Binding; Hippocampus (Brain); Image; In Vitro; Inhibitory Synapse; Knowledge; Lead; Mass Spectrum Analysis; Mediating; Membrane; Mental Retardation; Molecular; Molecular Weight; Mus; Nervous system structure; Neuraxis; Neuroglia; Neurons; Oligodendroglia; Peptide Hydrolases; Play; Preparation; Presynaptic Terminals; Process; Proteins; Proteomics; Recycling; Role; Secondary to; Series; Signal Transduction; Staging; Synapses; Testing; Therapeutic Intervention; Two-Dimensional Gel Electrophoresis; Variant; Vesicle; Whole-Cell Recordings; Work; cell type; excitatory neuron; inhibitory neuron; insight; monolayer; neurodevelopment; postsynaptic; presynaptic; release factor; research study; synaptic function; synaptogenesis

DESCRIPTION (provided by applicant): The assembly of CMS synapses is a complex and dynamic process, requiring the coordinated exchange of signals between pre- and postsynaptic neurons and surrounding glia. Astrocytes, one type of glia, have been shown to increase the formation and function of excitatory synapses, in part by releasing soluble factors as well as by contact. However/the role that astrocytes play in inhibitory synapse formation and function has not been well studied. It is the goal of this proposal to examine the role of astrocytes in inhibitory synaptogenesis in the developing nervous system. Previous work from the Balice-Gordon lab and my preliminary studies in hippocampal neurons in vitro suggest that astrocytes release soluble signals into the media (astrocyte conditioned media, ACM) that increase inhibitory neuron axon elongation, branching as well as synaptogenesis, by the criteria of increasing the number of GABAergic presynaptic terminals co-localized with postsynaptic GABAAR clusters (Elmariah et a I.", 2005; Hughes et al., 2005). My preliminary studies also suggest that neuronal contact with astrocytes, but not ACM, increase the number of functional GABAergic synapses. This leads to the hypothesis that secreted and contact signals from astrocytes differentially mediate the formation and function of inhibitory synapses during neural development. To test this hypothesis, I will: (1) Determine how astrocyte soluble signals affect inhibitory axon outgrowth, branching and synaptogenesis in a series of experiments. (2) Examine the role of neuron- astrocyte contact in the development of inhibitory synapse function. (3) Identify soluble signals released by astrocytes that increase inhibitory axon outgrowth, branching and synaptogenesis. Taken together, these experiments will extend our understanding of how inhibitory synapses are formed during neural development. The results of these studies will extend our understanding of how neuron-glia signaling modulates synapse formation and function, and set the stage for defining the underlying cellular and molecular mechanisms. Understanding these mechanisms will provide a foundation of knowledge that may, in the future, suggest avenues for therapeutic intervention for disorders of development such as epilepsy, autism and mental retardation, in which synapse formation and/or function are aberrant or reduced.

描述（由申请人提供）：CMS突触的组装是一个复杂而动态的过程，需要在突触前神经元和周围神经胶质的情况下协调交换信号。星形胶质细胞（一种类型的神经胶质）已被证明可以增加兴奋性突触的形成和功能，部分原因是通过释放可溶性因子和接触。但是，/星形胶质细胞在抑制突触形成和功能中所起的作用尚未得到很好的研究。该提案的目的是检查星形胶质细胞在发育中的神经系统中的抑制性突触发生中的作用。 BALICE-GORDON实验室的先前工作以及我在体外的海马神经元中的初步研究表明，星形胶质细胞将概念信号释放到培养基（星形胶质细胞调节的培养基，ACM）中，通过增加抑制性神经元伸长率的抑制性神经元伸长率，并通过增加gabaaptir distrial的标准，使抑制性神经元伸长率增加，并增加了抑制性神经元的伸长率。 Gabaar簇（Elmariah et a I.”，2005; Hughes等，2005）。我的初步研究还表明，神经元与星形胶质细胞的接触，但不是ACM，增加了功能性GABA能突触的数量。这导致了在构成中的秘密和触发性构成的造型和接触的构成，并在综合体系中进行了构成，并在造型中进行了构成。假设，我将：（1）确定星形胶质细胞可溶性信号如何影响抑制性轴突的生长，分支和突触发生在一系列实验中。 （3）确定由星形胶质细胞释放的可溶性信号，这些信号会增加抑制性轴突的生长，分支和突触发生。综上所述，这些实验将扩展我们对神经发育过程中抑制性突触的理解。这些研究的结果将扩展我们对神经元信号如何调节突触形成和功能的理解，并为定义下面的细胞和分子机制奠定了基础。理解这些机制将为知识提供基础，将来可能会为癫痫，自闭症和智力低下的发展疾病的治疗干预途径提出途径，在这种疾病中，突触形成和/或功能是异常或减少的。

项目成果

Cellular plasticity induced by anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor encephalitis antibodies.

• DOI: 10.1002/ana.24293
• 发表时间: 2015-03
• 期刊: ANNALS OF NEUROLOGY
• 影响因子: 11.2
• 作者: Peng, Xiaoyu;Hughes, Ethan G.;Moscato, Emilia H.;Parsons, Thomas D.;Dalmau, Josep;Balice-Gordon, Rita J.
• 通讯作者: Balice-Gordon, Rita J.