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Genetic and Physical Basis of Mechanical Neuroprotection

机械神经保护的遗传和物理基础

基本信息

批准号：
9005894
负责人：
Miriam B Goodman
金额：
$ 36.69万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-03-01 至 2020-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9005894
关键词：
Actins Acute Affect Afferent Neurons Anemia Animal Model Animals Axon Behavior Biochemical Biochemistry Biological Assay Blood capillaries Brain Diseases Caenorhabditis elegans Cell membrane Cells Collaborations Confocal Microscopy Cytoskeleton Defect Dendritic Spines Development Disease Dissection Erythrocytes Esthesia Fluorescence Resonance Energy Transfer Future Gene Transfer Techniques Genes Genetic Head Health Human Image In Vitro Injury Investigation Ion Channel Joints Knowledge Label Life Link Location Mammals Measures Mechanical Stress Mechanics Mechanoreceptors Modeling Molecular Morphology Motor Neurons Movement Muscle Mutation Nervous System Physiology Nervous system structure Neurites Neurons Neurosciences Organism Pain Physiology Predisposition Process Proprioception Protein Isoforms Proteins Research Risk Factors Role Sensory Signal Transduction Skin Spectrin Speed Stress Stretching Susceptibility Gene Testing Touch sensation Transcript Transgenic Animals Transgenic Organisms Translating Traumatic Brain Injury Work alpha Spectrin base beta Spectrin betaIV spectrin capillary cell type design digital imaging dimer experience flexibility image processing in vivo insight migration mutant neglect neuroprotection novel potential biomarker receptor relating to nervous system resilience response sensor somatosensory tool trafficking

项目摘要

DESCRIPTION (provided by applicant): The development and function of the nervous system is regulated not only by electrical and biochemical signals, but also by mechanical inputs. For instance, most if not all neurons generate mechanical stress and experience strain during migration, axon outgrowth, and dendritic spine remodeling. With a few notable exceptions, however, the study of cell mechanics has been neglected in neuroscience. We seek to fill this knowledge gap by investigating the genetic and physical basis of how neurons withstand mechanical stress focusing on C. elegans touch receptor neurons as a model. Key entry points for this investigation are the findings that loss of unc-70 ß spectrin function makes C. elegans neurons vulnerable to damage induced by normal movement and the well-known function for actin-spectrin networks in protecting red blood cells from the mechanical strains generated as they transit through tiny capillaries. In new work, we establish a simple visible assay for loss of spectrin function in the ventral touch receptor neurons and create transgenic animals expressing a genetically-encoded strain sensor that enables us to visualize how body bending and touch sensation affects stress in neural actin-spectrin networks. The proposed research combines genetic dissection, high-speed quantitative confocal microscopy, and in vitro biochemistry to investigate the role of spectrin networks in mechanical neuroprotection and sensory mechanoelectrical transduction. This work has the potential to transform understanding of neuronal cell mechanics and the contribution of actin-spectrin networks in this process. The new knowledge we seek to acquire could provide insight into the genetic basis of mechanical neuroprotection and potential risk factors related to traumatic brain injury.