THE ROLE OF ASTROCYTES IN PLASTICITY AND DISEASE.

描述(由申请人提供) 摘要：星形胶质细胞是人脑中含量最丰富的细胞类型，但目前对星形胶质细胞在人类疾病中的作用尚不完全清楚。在这项提案中，我们将开始使用几项新技术来揭示星形胶质细胞在调节皮质可塑性中的作用，这些新技术包括定量质谱学和微流控小室，用于快速识别星形胶质细胞因子，这些因子是响应旁分泌信号乙酰胆碱(ACh)或去甲肾上腺素(NE)而释放的，并且可能影响发育中和成年大脑的可塑性。此外，我们将利用加州大学旧金山分校杰出的干细胞和蛋白质组中心来研究自闭症患者的体细胞来源的星形胶质细胞是否分泌水平不同的突触生成因子。使用组合的微流室和成像系统，我们将使用来自自闭症患者和家族对照的星形胶质细胞来筛选对突触形成和功能的影响。这些研究有可能揭示神经胶质细胞在调节正常可塑性和疾病状态中的作用。 公共卫生相关性：这些研究将调查星形胶质细胞在自闭症谱系障碍和皮质可塑性中的作用。星形胶质细胞可以深刻地调节突触的形成和功能，而这两者在自闭症谱系障碍中都被破坏了。

DESCRIPTION (Provided by the applicant) Abstract: Astrocytes are the most abundant cell type in the human brain, yet we still do not fully understand the impact of astrocytes on human disease. In this proposal we will begin to uncover the role of astrocytes in regulating cortical plasticity using several new technologies including quantitative mass spectroscopy and microfluidic chambers developed to rapidly identify astrocyte factors that are released in response to the paracrine signals acetylcholine (ACh) or norepinephrine (NE) and that are likely to impact plasticity in both the developing and adult brain. Additionally, we will take advantage of the outstanding stem cell and proteomic centers here at UCSF to ask whether astrocytes derived from somatic cells from individuals on the autism spectrum secrete altered levels of synaptogenic factors. Using a combined microfluidic chamber and imaging system we will screen for effects on synapse formation and function using astrocytes derived from autism patients and familial controls. These studies have the potential to uncover the role of glial cells both in regulating normal plasticity and in disease states. Public Health Relevance: These studies will investigate the role of astrocytes in autism spectrum disorders and in cortical plasticity. Astrocytes can profoundly regulate synapse formation and function and both of these are disrupted in autism spectrum disorders.