Astrocytes in Down Syndrome Synaptogenesis

描述（由申请人提供）：唐氏综合症（DS）大脑中突触的结构和功能异常，导致这种发育障碍特有的认知缺陷。 过去十年的研究表明，除了突触前和突触后神经元之外，星形胶质细胞对于突触形成和可塑性也至关重要。 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 DS 小鼠模型中进行研究。 此 R03 应用的目的是研究 DS 星形胶质细胞是否导致 DS 中缺陷的突触形成和功能。 实验将利用来自 DS 小鼠模型 (Ts65Dn) 的细胞和人类 21 三体细胞，以确定星形胶质细胞对 DS 中树突生长、突触数量和突触功能的贡献。 这些试点实验的结果将提供对 DS 突触基本发育的深入了解，并将为进一步研究奠定基础，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。 项目叙述：作为智力低下最常见的遗传原因，唐氏综合症是一个公共健康问题。 拟议的研究将重点关注唐氏综合症患者大脑发育过程中神经细胞之间的通讯。 该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沟通中的作用，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.