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，促进了人类大脑疾病在发育和衰老方面的研究和治疗进展。本研究旨在建立一个广泛的普通狨猴（Callithrix jacchus）灵长类动物大脑数据库，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，但与旧世界的灵长类动物相比，它有一些优势，比如体积更小，繁殖双胞胎频繁，饲养简单。此外，由于狨猴的寿命短（8-12年），其成熟速度较短，因此在个体发育和衰老研究中特别具有吸引力。验证该模型首先需要建立正常组织变化的时间过程，从出生到成年，再到衰老。神经成像方法具有非侵入性和可生存性的关键优势，支持在长时间内进行基本上无限数量的连续测量。因此，我们将在三个特定的目标中评估新生儿、幼年、成年和老年狨猴群体，[1]通过T1加权解剖MRI对全脑、灰质、白质、脑回和脑沟的体积量化来描述大脑整体和区域结构的形态发展，[2]通过多参数T1、T2和DT MRI来描述白质组织形成，[3]定义未成熟皮层层的细胞结构微观结构；通过建立一个基于组织学的立体定位图谱，包括个体特征的分类分类和关键神经化学标记物的标记，成年和老年狨猴的大脑。我们的首要假设是，在人脑成像中观察到的与年龄相关的复杂时间变化将在狨猴大脑中得到密切反映，但时间常数缩短，反映了其较短的寿命。网络产品将提供几个全面的、描述性的发展数据集和一个可广泛传播的转化神经成像工具包。这一发现不仅扩大了方法学的范围，而且进一步证实了狨猴是一种有价值的灵长类动物，可用于模拟人类发育和衰老的大脑疾病，包括妊娠畸形、多发性硬化症、帕金森病和阿尔茨海默病。

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.