Mechanisms of Dendritic Spine Stability

树突棘稳定性的机制

基本信息

批准号：
7770038
负责人：
Shelley L Halpain
金额：
$ 37.96万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-12-04 至 2014-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7770038
关键词：
Actins Affect Autistic Disorder Binding Biochemical Biological Assay Brain Calmodulin Cell membrane Cell-Free System Cognition Disorders Dendrites Dendritic Spines Disease Doctor of Philosophy Enzymes F-Actin Fluorescence Recovery After Photobleaching Glutamate Receptor Goals Hippocampus (Brain)Image Individual Life Link Location Long-Term Depression Maintenance Mediating Membrane Microfilaments Molecular Mood Disorders Morphology Nerve Neurodegenerative Disorders Neurologic Neurons Pathway interactions Phosphatidylinositol 4,5-Diphosphate Phosphatidylinositols Phospholipids Phosphoric Monoester Hydrolases Phosphorylation Phosphotransferases Physiological Play Property Protein Kinase C Proteins RNA Interference Regulation Rodent Role Series Shapes Signal Transduction Site Stroke Structure Synapses Synaptic plasticity Synaptophysin Testing Time Vertebral column Work cell fixing cofilin combat computerized data processing density fluorescence imaging mutant myristoylated alanine-rich C kinase substrate neuropsychiatry novel polymerization postsynaptic presynaptic public health relevance research study response therapy design

项目摘要

DESCRIPTION (provided by applicant): The long-term goal of this project is to identify molecular mechanisms that regulate the stability and plasticity of dendritic spines, small postsynaptic structures that play key roles in signal processing in neuronal circuits. Disruptions of spine numbers and shape occur in many neurological and neuropsychiatric diseases, including mood disorders, autism, and neurodegenerative disease. The size and shape of spines correlates with the physiological strength of the synapse, thus understanding the key molecular pathways that regulate spine shape and stability are crucial for designing therapies to combat such cognitive diseases. This project will focus on a central molecular pathway controlling spine shape and stability that involves the protein MARCKS. Using quantitative fluorescence imaging in dissociated cultures of rodent neurons, the project will characterize the function of MARCKS in dendritic spines using cellular and molecular approaches. Project objectives are to identify the interaction of MARCKS with downstream effectors and their influence on actin filaments and synaptic protein assemblies. PUBLIC HEALTH RELEVANCE: The long-term goal of this project is to identify molecular mechanisms that regulate the stability and plasticity of dendritic spines, small postsynaptic structures that play key roles in signal processing in neuronal circuits. Disruptions of spine numbers and shape occur in many neurological and neuropsychiatric diseases, including mood disorders, autism, stroke, and neurodegenerative disease. The size and shape of spines correlates with the physiological strength of the synapse, thus understanding the key molecular pathways that regulate spine shape and stability are crucial for designing therapies to combat such cognitive diseases. This project will focus on a central molecular pathway controlling spine shape and stability that involves the protein MARCKS and the signaling phospholipid PIP2. Using quantitative fluorescence imaging in dissociated cultures of rodent neurons, the project will characterize the function of MARCKS in dendritic spines using cellular and molecular approaches. Project objectives are to identify the interaction of MARCKS with downstream effectors and their influence on actin filaments and synaptic protein assemblies.

描述（由申请人提供）：该项目的长期目标是确定调节树突状棘的稳定性和可塑性的分子机制，在神经元电路中信号处理中起关键作用的小突触后结构。脊柱数量和形状的干扰发生在许多神经系统和神经精神疾病中，包括情绪障碍，自闭症和神经退行性疾病。刺的大小和形状与突触的生理强度相关，因此了解调节脊柱形状和稳定性的关键分子途径对于设计疗法以对抗这种认知疾病至关重要。该项目将集中于控制脊柱形状和稳定性的中央分子途径，涉及蛋白质马克克斯。该项目使用啮齿动物神经元的分离培养物中的定量荧光成像，使用细胞和分子方法来表征马克克斯在树突状棘中的功能。项目目标是确定马克克人与下游效应子的相互作用及其对肌动蛋白丝和突触蛋白组件的影响。公共卫生相关性：该项目的长期目标是确定调节树突状棘的稳定性和可塑性的分子机制，在神经元电路中信号处理中起关键作用的突触后结构的小小的突触后结构。脊柱数量和形状的干扰发生在许多神经系统和神经精神疾病中，包括情绪障碍，自闭症，中风和神经退行性疾病。刺的大小和形状与突触的生理强度相关，因此了解调节脊柱形状和稳定性的关键分子途径对于设计疗法以对抗这种认知疾病至关重要。该项目将集中于控制脊柱形状和稳定性的中央分子途径，涉及蛋白质MARCK和信号磷脂PIP2。该项目使用啮齿动物神经元的分离培养物中的定量荧光成像，使用细胞和分子方法来表征马克克斯在树突状棘中的功能。项目目标是确定马克克人与下游效应子的相互作用及其对肌动蛋白丝和突触蛋白组件的影响。