Astrocytes in Down Syndrome Synaptogenesis

描述(申请人提供)：唐氏综合征(DS)大脑中突触的结构和功能异常，导致以这种发育障碍为特征的认知缺陷。过去十年的研究表明，除了突触前和突触后的神经元，星形胶质细胞对突触的形成和可塑性也是至关重要的。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突触发育中的作用还没有在人类或小鼠DS模型中进行研究。此R03应用的目的是研究DS星形胶质细胞是否参与DS中有缺陷的突触的形成和功能。这些实验将利用来自DS小鼠模型(Ts65Dn)的细胞和人类21三体细胞，来确定星形细胞对DS中树突状细胞生长、突触数量和突触功能的贡献。这些先导性实验的结果将提供对DS突触基本发育的洞察，并将形成进一步研究的基础，以确定星形胶质细胞支持的性质以及测试改善DS突触发育的潜在治疗策略。 项目简介：唐氏综合症是导致精神发育迟缓的最常见的遗传原因，是一个公共卫生问题。这项拟议的研究将重点放在唐氏综合症患者大脑发育过程中神经细胞之间的通讯。这项研究的目的是确定星形胶质细胞或支持细胞在塑造神经细胞之间的通信中所起的作用，以及它们在唐氏综合症中是否功能失调。

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.