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

描述(由申请人提供)：通过使用适当的研究动物模型，促进了对发育和衰老中的人类大脑疾病的研究和治疗的进展。这项提议寻求建立一个广泛的灵长类动物大脑数据库，以确定常见绒猴(Callithrix Jacchus)在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。绒猴的大脑非常复杂，是人类神经和精神疾病的原型，但与东半球的灵长类物种相比，它具有优势，如较小的体积、频繁的生殖双胞胎和简单的饲养。此外，短命(8-12年)的绒猴由于其压缩的成熟率而在个体发育和衰老研究中特别有吸引力。要验证这个模型，首先需要建立正常组织从出生到成年再到衰老的时间过程。神经成像方法提供了非侵入性和可存活性的关键优势，支持在较长时间内进行基本上无限数量的连续测量。因此，我们将在三个特定目标上对新生儿、青少年、成年和老年绒猴群体进行评估，[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局部脑结构的形态发展，[2]通过使用多参数T1、T2和DT MRI来描述白质组织的形成，以及[3]通过建立基于组织学的立体分类图谱来定义未成熟、成年和老年绒猴脑中皮质层的细胞结构微结构，以包括对个体特征的分类和关键神经化学标记的标记。我们的主要假设是，通过成像在人脑中观察到的与年龄相关的变化的复杂时间分布将密切反映在绒猴大脑中，但时间常数缩短反映了其较短的寿命。Net产品将提供几个全面的描述性发育数据集和一个可广泛传播的翻译神经成像工具包。这些发现不仅应该扩大方法学，而且还将进一步验证绒猴作为建模人类发育和衰老大脑疾病的有价值的灵长类对象，包括妊娠畸形、多发性硬化症、帕金森氏症和阿尔茨海默病。

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.