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Investigating Astrocyte Diversity and Function in Midbrain Dopaminergic Circuits

研究中脑多巴胺能回路中星形胶质细胞的多样性和功能

基本信息

批准号：
8442735
负责人：
Erik M Ullian
金额：
$ 27.42万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-12-20 至 2015-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8442735
关键词：
Ablation Affect Astrocytes Atlases Attention deficit hyperactivity disorder Axon Biology Brain Brain Stem Brain region Candidate Disease Gene Cell Nucleus Cells Cues Data Data Set Databases Development Disease Dorsal Erinaceidae Fibrous Astrocyte Functional disorder Genes Glues Human In Situ Label Lead Measures Mediating Mental Health Mental disorders Messenger RNA Methods MicroRNAs Midbrain structure Molecular Molecular Profiling Mus Nerve Neurobiology Parkinson Disease Pattern Population Regulation Role Schizophrenia Semaphorin-3A Specific qualifier value Substantia nigra structure Testing Text To specify Transgenic Mice Transgenic Organisms Ventral Tegmental Area Western Blotting abstracting axon guidance clinically relevant dopaminergic neuron embryonic stem cell hindbrain in vivo insight nervous system disorder neural circuit novel tool transcription factor

项目摘要

Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. ABSTRACT Recent studies indicate that astrocytes are spatially diversified, which may have consequence for psychiatric diseases with regional brain dysfunction. However, establishing diversified functions of astrocytes in brain development and disease has been limited by a lack of tools for lineage-specific astrocyte manipulation. Recently, we developed novel transgenic methods to label, purify and characterize regional astrocyte populations in mouse brain. The midbrain and brainstem contain dopaminergic nuclei of the ventral tegmental area (VTA) and substantia nigra (SN) that are implicated in schizophrenia, ADHD and Parkinson's disease. We will test the hypothesis that regionally-specified astrocytes from the ventral midbrain are uniquely suited to support survival and connectivity of dopaminergic projections from the VTA and SN. We will determine molecular diversity of region-restricted midbrain astrocytes as a first step towards uncovering the role of regionally diverse astrocytes in neurological disorders. Deliverables include validated transgenic mouse tools for conditional temporal- spatial labeling, purification of astrocytes throughout the CNS as well as markers of regionally heterogeneous astrocytes subtypes of mid/hindbrain compiled into a public database. The project is intended to reveal signatures of astrocyte subtypes and provide insight into the role of astrocytes in mental health.

在此处输入文本，这是您的应用程序的新摘要信息。本节必须是否超过30行的文本。摘要最近的研究表明，星形胶质细胞在空间上是多样化的，这可能具有精神疾病的后果与区域性脑功能障碍。然而，在这方面，建立星形胶质细胞在大脑发育和疾病中的多种功能由于缺乏谱系特异性星形胶质细胞操作的工具而受到限制。最近，我们开发了新的转基因方法来标记，纯化和表征小鼠脑中的局部星形胶质细胞群体。中脑和脑干含有腹侧被盖的多巴胺能核团区域（VTA）和黑质（SN）与精神分裂症，ADHD有关和帕金森氏症我们将测试假设，来自腹侧中脑的星形胶质细胞特别适合于支持生存， VTA和SN的多巴胺能投射的连接性。我们将确定区域限制性中脑星形胶质细胞的分子多样性作为迈向揭示了不同区域星形胶质细胞在神经系统疾病中的作用。可供选择的工具包括经验证的转基因小鼠工具，用于条件性时间- 整个中枢神经系统星形胶质细胞的空间标记、纯化以及标记物中/后脑的区域异质性星形胶质细胞亚型编译成一个公共数据库。该项目旨在揭示星形胶质细胞的特征亚型，并提供洞察星形胶质细胞在心理健康中的作用。