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.
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