A Neuroimaging Study of Primate Brain Development and Aging in the Marmoset

灵长类狨猴大脑发育和衰老的神经影像学研究

• 批准号: 7494095
• 负责人: MICHAEL DUFF DAVIS
• 金额: $ 32万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-15 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7494095
• 关键词: Adolescent; Adult; Affect; Age; Aging; Alzheimer' s Disease; Animal Experimentation; Animal Model; Animals; Anisotropy; Archives; Atlases; Australia; Biochemical Markers; Biomedical Research; Birth; Body of uterus; Brain; Brain Diseases; Brain imaging; Breeding; Callithrix; Callithrix jacchus jacchus; Cell Nucleus; Cerebellum; Cerebrum; Classification; Complement; Complex; Data; Data Set; Databases; Development; Diffusion Magnetic Resonance Imaging; Disease; Dysmorphology; Foundations; Funding; Goals; Health Sciences; Hippocampus (Brain); Histologic; Human; Image; Image Analysis; Individual; Invasive; Label; Life; Life Cycle Stages; Longevity; Macaca mulatta; Magnetic Resonance Imaging; Maps; Measurement; Measures; Mental disorders; Methods; Minor; Mission; Modality; Modeling; Molecular; Multiple Sclerosis; Myelin; Neonatal; Nerve Degeneration; Neurobiology; Neurologic; New South Wales; Normal tissue morphology; Numbers; Parkinson Disease; Pathology; Pattern; Physiologic pulse; Primates; Process; Protocols documentation; Pulse taking; Purpose; Range; Rate; Research; Research Personnel; Resolution; Resources; Staging; Structure; Surface; Texas; Therapeutic; Thick; Time; Tissue Harvesting; Tissues; Translations; Twin Multiple Birth; Universities; Validation; Weight; Width; age related; aged; aging brain; base; brain volume; gray matter; human disease; indexing; knowledge base; morphometry; myelination; neurochemistry; neuroimaging; programs; reproductive; senescence; size; ultra high resolution; white matter

DESCRIPTION (provided by applicant): Progress in the study and treatment of human brain disease in development and aging is facilitated by use of appropriate research animal models. This proposal seeks to build an extensive primate brain database of the common marmoset (Callithrix jacchus) that will define the evolving changes in anatomical structure, myelination processes and neurochemical patterns across the animal's entire life cycle. The marmoset brain is remarkably complex and is an archetype of human neurological and psychiatric disorders, yet has advantages over old-world primate species, such as its smaller size, frequent reproductive twinning and simple husbandry. Moreover, a short life span (8-12yrs) makes the marmoset particularly attractive in ontogenetic and aging studies by virtue of its compressed rate of maturation. Validation of this model first requires establishing the temporal course of normal tissue changes from birth through adulthood and into senescence. Neuroimaging methods offer key advantages of being non-invasive and survivable, supporting an essentially unlimited number of sequential measurements over a prolonged period. Thus we will evaluate neonatal, juvenile, adult and aged marmoset groups in 3 specific aims by, [1] Describing the morphological development of global and regional brain structures through volumetric quantification of whole-brain, gray matter, white-matter, gyri and sulci using T1-weighted anatomical MRI, [2] Profiling white-matter tissue formation by employing multi-parametric T1, T2 and DT MRI, and [3] Defining the cytoarchitectonic microstructure of cortical layers in immature, adult and aged marmoset brains by building a histologically- based stereotaxic atlas to include the taxonomic classification of individual features and labeling of key neurochemical markers. Our overarching hypothesis is that the complex temporal profiles of age-related changes observed with imaging in the human brain will be closely mirrored in the marmoset brain, but with shortened time constants reflecting its shorter life span. The net product will provide several comprehensive, descriptive developmental datasets and a translational neuroimaging toolkit that can be broadly disseminated. The findings should not only expand the methodological armamentaria, but also further validate the marmoset as a valuable, primate subject for modeling human developmental and aging brain disorders, including gestational dysmorphology, multiple sclerosis, Parkinson's and Alzheimer's Disease.

描述（由申请人提供）：通过使用适当的研究动物模型，促进了人类大脑发育和衰老疾病的研究和治疗的进展。该提案旨在建立一个广泛的普通狨猴（Callithrix jacchus）灵长类大脑数据库，该数据库将定义动物整个生命周期中解剖结构、髓鞘形成过程和神经化学模式的演变变化。狨猴的大脑非常复杂，是人类神经和精神疾病的原型，但与旧世界灵长类动物相比具有优势，例如体积较小、频繁的生殖双胞胎和简单的饲养。此外，狨猴的寿命较短（8-12岁），由于其成熟速度较慢，因此在个体发育和衰老研究中特别有吸引力。验证该模型首先需要确定正常组织从出生到成年再到衰老的时间过程。神经影像方法具有非侵入性和可生存的关键优势，支持在较长时间内进行基本上无限数量的连续测量。因此，我们将通过以下 3 个具体目标评估新生儿、幼年、成年和老年狨猴群体：[1] 通过使用 T1 加权解剖 MRI 对全脑、灰质、白质、脑回和脑沟进行体积量化来描述整体和区域大脑结构的形态发育，[2] 通过采用多参数 T1、T2 和 DT 分析白质组织形成 MRI，以及[3]通过构建基于组织学的立体定位图谱来定义未成熟、成年和老年狨猴大脑皮质层的细胞结构微观结构，包括个体特征的分类和关键神经化学标记物的标记。我们的总体假设是，通过人脑成像观察到的与年龄相关的变化的复杂时间曲线将密切反映在狨猴大脑中，但时间常数缩短反映了其较短的寿命。该净产品将提供几个全面的、描述性的发育数据集和一个可以广泛传播的转化神经影像工具包。这些发现不仅扩大了方法论的范围，而且还进一步验证了狨猴作为一种有价值的灵长类动物模型，可用于模拟人类发育和衰老脑部疾病，包括妊娠畸形、多发性硬化症、帕金森病和阿尔茨海默病。