A NEUROIMAGING STUDY OF PRIMATE BRAIN DEVELOPMENT AND AGING IN THE MARMOSET

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 通过使用适当的研究动物模型，促进了在发育和衰老中的人脑疾病的研究和治疗的进展。该提案旨在建立一个广泛的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。绒猴的大脑非常复杂，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，绒猴具有优势，例如体积较小，频繁的生殖孪生和简单的饲养。此外，短寿命（8- 12岁）使绒猴在个体发育和衰老研究中特别有吸引力，因为它的成熟率很低。这个模型的验证首先需要建立正常组织从出生到成年和衰老的变化的时间过程。神经影像学方法提供了非侵入性和可存活性的关键优势，支持在长时间内基本上无限数量的连续测量。因此，我们将在3个特定目标中评估新生、幼年、成年和老年绒猴组，[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定量来描述整体和局部脑结构的形态发育，[2]通过使用多参数T1、T2和DT MRI对白质组织形成进行分析，以及[3]通过建立基于组织学的立体定位图谱，包括个体特征的分类学分类和关键神经化学标记物的标记，确定未成熟、成年和老年绒猴脑皮质层的细胞结构微结构。我们的总体假设是，在人类大脑中观察到的与年龄相关的变化的复杂时间曲线将在绒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。该网络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翻译神经成像工具包。这些发现不仅扩大了方法学的武器，而且还进一步验证了绒猴作为一种有价值的灵长类动物，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。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.