In vivo cellular imaging of myelin plasticity and regeneration in cortical gray m

皮质灰质髓磷脂可塑性和再生的体内细胞成像

基本信息

批准号：
8684056
负责人：
Jaime Grutzendler
金额：
$ 24.98万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8684056
关键词：
2 year old Ablation Address Adult Affect Age Aging Animals Attention Axon Biological Neural Networks Birth Breeding Cells Cessation of life Data Demyelinating Diseases Demyelinations Dependence Designer Drugs Development Dyes Elderly Employee Strikes Excision Fiber Grant Gray unit of radiation dose Image Imaging Techniques Individual Injury Knowledge Label Lasers Left Length Life Lipids Live Birth Maintenance Medicine Mental disorders Methods Microscopy Mus Mutant Strains Mice Myelin Myelin Sheath Natural regeneration Nature Neuraxis Neurodegenerative Disorders Neuronal Plasticity Neurons Oligodendroglia Pathology Pattern Peripheral Nerves Process Production Proteins Refractive Indices Resolution Role Sensory Sensory Deprivation Signal Transduction Spinal Cord Staging Structure Techniques Testing Time Transgenic Mice Vibrissae Viral Vector Wild Type Mouse aged base brain volume cellular imaging density dysmyelination environmental enrichment for laboratory animals fluorescence imaging gray matter imaging modality in vivo in vivo imaging insight myelination neocortical nervous system disorder neuronal patterning novel postnatal progenitor public health relevance receptor relating to nervous system remyelination research study tool two-photon white matter

项目摘要

DESCRIPTION (provided by applicant): Myelin is a fundamental component of mature neural networks that is affected in a large number of pathological conditions of the central nervous system (CNS). Critical for advancing knowledge about these conditions would be a better in vivo understanding of how oligodendrocytes and their respective myelin sheaths develop, are maintained throughout life and respond to injury. We have developed a new technique that allows high resolution label-less in vivo imaging of myelinated axons. This technique takes advantage of the high refractive index of lipid rich multilayered myelin and is based on multispectral confocal reflectance (MCORE) microscopy. Using MCORE we have obtained for the first time long- term images of the dynamics of cortical myelin on the cellular scale in a livig animal. Our preliminary data shows this technique as well as fluorescence imaging are a powerful set of tools that in combination provide a wealth of information about fine structural changes in oligodendrocytes and myelin in vivo. We demonstrate the feasibility to track the development of myelin pathology in a dysmyelinating mutant mouse and determine the temporal dynamics of demyelination after single oligodendrocyte ablation. We propose to use this powerful technique in combination with in vivo two-photon and confocal fluorescence imaging to address three fundamental questions concerning the plasticity and regeneration of neocortical myelin. First, we will determine the long-term in vivo dynamics of individual oligodendrocytes and myelinated axons from birth to death. Second, we will investigate how neuronal activity influences myelin formation and stability on individually active axons in vivo. Finally we will stuy the process of demyelination and remyelination after single oligodendrocyte ablation and determine how repeated ablation and neuronal activity influences the temporal dynamics of remyelination. Together these experiments will provide novel insight into the fundamental plasticity and regeneration capabilities of myelin and oligodendrocytes in relation to axonal activity throughout life.

描述（由申请人提供）：髓磷脂是成熟神经网络的基本组成部分，在中枢神经系统（CNS）的大量病理状况中受到影响。增进对这些疾病的了解的关键是更好地了解少突胶质细胞及其各自的髓鞘如何发育、在整个生命过程中维持以及对损伤的反应的体内了解。我们开发了一种新技术，可以对有髓轴突进行高分辨率无标记体内成像。该技术利用富含脂质的多层髓磷脂的高折射率，并基于多光谱共焦反射 (MCORE) 显微镜。使用 MCORE，我们首次获得了活体动物细胞尺度上皮质髓磷脂动态的长期图像。我们的初步数据表明，该技术以及荧光成像是一套强大的工具，它们结合起来提供了有关体内少突胶质细胞和髓磷脂精细结构变化的丰富信息。我们证明了跟踪髓鞘形成障碍突变小鼠髓鞘病理学发展并确定单个少突胶质细胞消融后脱髓鞘时间动态的可行性。我们建议将这种强大的技术与体内双光子和共焦荧光成像相结合，以解决有关新皮质髓磷脂的可塑性和再生的三个基本问题。首先，我们将确定单个少突胶质细胞和有髓轴突从出生到死亡的长期体内动态。其次，我们将研究神经元活动如何影响体内单个活性轴突的髓磷脂形成和稳定性。最后，我们将研究单次少突胶质细胞消融后脱髓鞘和髓鞘再生的过程，并确定重复消融和神经元活动如何影响髓鞘再生的时间动态。这些实验将为了解髓磷脂和少突胶质细胞的基本可塑性和再生能力与整个生命过程中轴突活动的关系提供新的见解。