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来促进人脑疾病的研究和治疗人类脑疾病的进展。该提案旨在建立一个广泛的灵长类动物脑数据库（Callithrix jacchus），该数据库将定义整个动物整个生命周期的解剖结构，髓鞘化过程和神经化学模式的不断变化。 Marmoset的大脑非常复杂，是人类神经和精神疾病的原型，但比旧世界的灵长类动物具有优势，例如其较小的尺寸，频繁的生殖孪生和简单的饲养。此外，短期寿命（8-12岁）使Marmoset凭借其成熟速率在个体发生和衰老研究中特别有吸引力。该模型的验证首先需要确定正常组织的时间过程，从出生到成年再到衰老。神经影像学方法提供了非侵入性和可生存的关键优势，从而在长时间内支持了基本无限数量的顺序测量。因此，我们将通过[1]评估3个特定目的的新生儿，少年，成人和年龄的果酱组[1]，通过对全脑，灰质，白色物质，白色物质，gyri，gyri，gyri和sulci的大量定量，使用T1加权的解剖学划分的乘以乘以乘以五个以下的五个以下杂物，来描述全球和区域大脑结构的形态发展，并使用T1-- MRI和[3]通过构建基于组织学的立体定量图集，定义未成熟，成人和老化的Marmoset大脑中皮质层的细胞结构微观结构，以包括对个体特征的分类分类和关键神经化学标记的标记。我们的总体假设是，在人脑中观察到的与年龄相关的变化的复杂时间概况将在摩尔莫斯特脑中紧密反映，但是时间常数缩短，反映了其较短的寿命。净产品将提供几种全面的描述性发展数据集和一个可以广泛传播的转化神经影像学工具包。这些发现不仅应该扩大方法论中的武术，而且还应进一步验证摩尔马斯群岛作为对人类发育和衰老脑部疾病进行建模的宝贵，灵长类动物的验证，包括妊娠畸形，多发性硬化症，帕金森氏症，帕金森氏症和阿尔茨海默氏病。