MOLECULAR REGULATION OF NEURONAL GAP JUNCTIONS DURING DEVELOPMENT AND INJURY

发育和损伤过程中神经元间隙连接的分子调控

• 批准号: 7959578
• 负责人: ANDREI B BELOUSOV
• 金额: $ 5.87万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959578
• 关键词: Adult; CREB1 gene; Cell Death; Cells; Computer Retrieval of Information on Scientific Projects Database; Connexins; Coupling; Development; Dyes; Electrical Synapse; Embryo; Event; Funding; GABA-A Receptor; Gap Junctions; Grant; Hypothalamic structure; In Vitro; Injury; Institution; Life; Mediating; Metabotropic Glutamate Receptors; Modeling; Molecular; Molecular Biology; Nervous system structure; Neuronal Differentiation; Neuronal Injury; Neurons; Northern Blotting; Play; Rattus; Regulation; Research; Research Personnel; Resources; Role; Shock; Source; Staining method; Stains; Testing; United States National Institutes of Health; Up-Regulation; Western Blotting; connexin 36; neural circuit; novel strategies; postnatal; synaptogenesis

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In the mammalian nervous system, coupling of neurons by gap junctions (GJs; electrical synapses) increases during embryonic and/or early postnatal development and plays an important role in a number of developmental events, including neuronal differentiation, cell death, synaptogenesis and neural circuit formation. GJ coupling subsequently decreases and remains low in the adult, confined to specific subsets of neurons. In the mature nervous system, GJ coupling increases during a number of pathological conditions, including traumatic and ischemic injuries. However, the mechanisms that are responsible for increases in neuronal GJ coupling during development and injuries are unknown. They will be studied in the proposed research in rat hypothalamic neuronal cultures. First, we will test the hypothesis that increase in neuronal GJ coupling during development is regulated by GABA-A receptors and group II metabotropic glutamate receptors via CREBdependent regulation of the main neuronal connexin, connexin 36 (Cx36). This will be tested using molecular biology, dye coupling, western blots, northern blots, and staining for live neurons. Second, we will test the hypothesis that the mechanisms that are responsible for developmental up-regulation of neuronal gap junctions also are responsible for gap junction up-regulation during neuronal injury. Therefore, the role of GABA-A receptors, group II metabotropic glutamate receptors, and CREB in the neuronal injury-mediated increases in gap junction coupling will be tested. Hypoosmotic shock will be used as an in vitro neuronal injury model. The proposed research may help to understand the mechanisms of neuronal injuries and to develop new approaches for the treatment of injuries.

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