Astrocytes in Down Syndrome Synaptogenesis

描述（申请人提供）：唐氏综合症（DS）大脑突触的结构和功能异常，导致认知缺陷，这是这种发育障碍的特征。过去十年的研究表明，除了突触前和突触后神经元外，星形胶质细胞对突触的形成和可塑性至关重要。星形胶质细胞控制树突生长、突触发生、突触功能和突触可塑性。星形胶质细胞在DS突触发育中的作用尚未在人类或小鼠DS模型中得到研究。本R03应用的目的是研究DS星形胶质细胞是否参与了DS中有缺陷的突触形成和功能。该实验将利用来自DS小鼠模型（Ts65Dn）和人类21三体细胞的细胞，来确定星形胶质细胞对DS树突生长、突触数量和突触功能的贡献。这些初步实验的结果将为进一步研究星形胶质细胞支持的性质以及测试潜在的治疗策略以改善DS突触的发育提供基础，并为DS突触的基本发育提供见解。

DESCRIPTION (Provided by Applicant): The structure and function of synapses in Down syndrome (DS) brain are abnormal, causing the cognitive deficits that characterize this developmental disorder. Research within the last decade has revealed that, in addition to pre- and post-synaptic neurons, astrocytes are critical to synapse formation and plasticity. Astrocytes control dendritic growth, synaptogenesis, synapse function, and synaptic plasticity. The role of astrocytes in DS synapse development has not been studied in either humans or in mouse models of DS. The objective of this R03 application is to investigate whether DS astrocytes contribute to the defective synapse formation and function in DS. The experiments will utilize both cells from a DS mouse model (Ts65Dn) and human trisomy 21 cells, to define the contribution of astrocytes to dendritic growth, synapse number, and synapse function in DS. Results from these pilot experiments will provide insight into the fundamental development of DS synapses, and will form the basis for further studies to define the nature of the astrocyte support as well as test potential therapeutic strategies to improve synaptic development in DS. PROJECT NARRATIVE: As the most common genetic cause of mental retardation, Down syndrome is a public health concern. The proposed research will focus on the communication among nerve cells in Down syndrome as the brain develops. The aim of the research is to define the role of astrocytes, or support cells, in shaping the communication among nerve cells, and whether they are dysfunctional in Down syndrome.