Understanding cellular architecture of the neurovascular unit and its function in the whole mouse brain

了解神经血管单元的细胞结构及其在整个小鼠大脑中的功能

基本信息

批准号：
9919633
负责人：
Yongsoo Kim
金额：
$ 59.14万
依托单位：
PENNSYLVANIA STATE UNIV HERSHEY MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9919633
关键词：
3-Dimensional Active Sites Affect Aging Albumins Alzheimer&apos s Disease Anatomy Animals Architecture Area Atherosclerosis Blood Vessels Brain Brain Diseases Brain Mapping Brain region Caliber Cells Cerebrum Communities Complex Data Data Set Environment Female Fluorescein Foundations Gel Genetic Goals Health Heterogeneity Homeostasis Image Impaired cognition Infrastructure Infusion procedures Injury Internet Interneurons Label Lead Link Maps Mediating Metabolic Methods Microanatomy Modeling Mus Neocortex Neuroglia Neurologic Neurons Nitric Oxide Nitric Oxide Synthase Type I Nutrient Online Systems Oxygen Parvalbumins Pathologic Pathology Pericytes Physiological Play Regulation Reporter Research Personnel Resolution Resources Role Sensory Signaling Molecule Smooth Muscle Myocytes Specificity Stroke Structure Surface Symptoms System Trees Vascular blood supply Vasoactive Intestinal Peptide Vasodilation Vasomotor Vibrissae Visualization Whole Organism Work age related aged awake base blood perfusion brain health cell motility cell type cerebral microvasculature cognitive function computerized tools excitatory neuron human disease in vivo in vivo calcium imaging innovation insight male nervous system disorder neural circuit neuropathology neuropeptide Y neurovascular neurovascular coupling neurovascular unit new technology novel optogenetics relating to nervous system response skills somatosensory submicron tomography tool two-photon wasting

项目摘要

ABSTRACT An intricate web of blood vessels in the mammalian brain provides essential oxygen and nutrients to power the energy demands of the brain. The structure of the brain’s microvasculature provides the extraordinary surface needed for a high level of energy exchange and clearance of metabolic wastes. Small vessel pathologies are involved in cognitive decline associated with aging and many brain disorders. Mounting evidence supports the idea that neuronal activity dynamically regulates diameter of small vessels to maintain energy homeostasis. For example, when mice use their whiskers to sense the external environment, neural activity in corresponding somatosensory areas increases and small vessels in the area dilate to increase blood perfusion. Cortical interneurons, especially neuronal nitric oxide synthase (nNOS) expressing neurons, are the major cell type to mediate such neurovascular coupling. Interestingly, emerging evidence suggests that 3D distribution and function of small vessels, and their interaction with vasomotor neurons are heterogeneous in different brain regions. Moreover, some brain regions are more susceptible than others to age related degeneration, which can be linked to many neurological conditions with brain region specific symptoms such as Alzheimer's disease. To understand the underlying neurovascular mechanisms affected in health and pathological conditions, we propose to create a precise 3D map of micro vessels and cell types controlling vessel motility in the entire mammalian brain using the mouse as a model. Furthermore, we aim to gain a comprehensive understanding of neurovascular changes during aging. Towards this goal, we have created a synergistic collaborative team with complementary skill sets to establish high-resolution whole mouse brain anatomical maps of micro vessels and nNOS interneurons subtypes (Dr. Kim), to establish a web-visualization to widely disseminate these maps (Dr. Cheng), and to study functional relationships involved in the regulation of vasomotility from awake animals (Dr. Drew). The proposed work will establish reference maps that are needed as a foundation for the further study of neurovascular architectures supporting normal cognitive function and their changes in various neuropathologies.

抽象的哺乳动物大脑中复杂的血管网络提供了本质的氧气和营养，以供电大脑的能量需求。大脑微脉管系统的结构提供了非凡的表面高能量交换和代谢废物的清除所需。小血管病理是参与与衰老和许多脑部疾病相关的认知下降。安装证据支持神经活性动态调节小血管直径以维持能量稳态的想法。例如，当小鼠使用晶须感知外部环境时，相应的神经活动体感区域增加，该地区的小血管扩张以增加血液灌注。皮质中间神经元，尤其是表达神经元的神经元一氧化氮合酶（NNOS），是主要细胞类型介导这种神经血管耦合。有趣的是，新兴的证据表明3D分布和小血管的功能及其与血管舒缩神经元的相互作用在不同的大脑中是异质的地区。此外，某些大脑区域比其他与年龄有关的变性更容易受到影响，这可以与许多具有大脑区域特定症状的神经系统疾病有关，例如阿尔茨海默氏症疾病。了解健康和病理影响的潜在神经血管机制条件，我们建议创建一个微血管和细胞类型的精确3D图，以控制血管运动性使用小鼠作为模型的整个哺乳动物大脑。此外，我们旨在获得全面的了解衰老过程中神经血管变化。为了实现这一目标，我们创造了一种协同作用协作团队具有完善的技能，以建立高分辨率全鼠标大脑解剖微血管和NNOS中间神经元亚型的地图（Kim博士），以建立一个广泛的网络视觉化传播这些地图（Cheng博士），并研究与调节有关的功能关系血管舒张症来自清醒动物（Drew博士）。拟议的工作将建立所需的参考图作为对支持正常认知功能和他们在各种神经病理学方面的变化。