Nonhuman Primate Core

总结：非人灵长类核心

SUMMARY: NONHUMAN PRIMATE CORE There is a critical unmet need to develop increasingly sophisticated animal models that will provide insights in the brain mechanisms that may underlie the development of schizophrenia (SZ) and inform the development of novel therapeutic interventions for this illness. While the underlying causes of the illness remain unknown, converging evidence suggests that SZ is a neurodevelopmental brain disease resulting from a combination of genetic and environmental risk factors. Our group is using cross-species, complimentary approaches to examine one potential etiology of SZ – changes in the prenatal immune environment that alter brain and behavioral development of the offspring. Evidence from epidemiological studies has shown that exposure to a variety of infections during pregnancy is associated with an increased risk of having a child later develop SZ. Rodent models have played a critical role in establishing causal relationships between the activated maternal immune system and aberrant brain and behavior development in the offspring. The long term objective of the Nonhuman Primate (NHP) Core is to bridge the gap between human studies and rodent models, and evaluate the disease relevance of maternal immune activation (MIA) in a model system more closely related to humans – the rhesus monkey. To accomplish this objective, we will undertake three specific aims. First the NHP core will sample and distribute archived brain tissue from an initial cohort of rhesus monkeys prenatally exposed to MIA to Projects 1 and 2 to evaluate the cellular and molecular pathology underlying aberrant behaviors of MIA offspring. Second, the NHP core will generate a new cohort of MIA and control macaque offspring needed to carry out a highly integrated series of structural, functional and molecular neuroimaging studies in Projects 3 and 4. Finally, the NHP core will conduct a comprehensive assessment of the behavioral development of the new cohort of MIA and control macaque offspring using novel measures that probe the core features of SZ. This interconnected evaluation of brain and behavioral development of monkeys prenatally exposed to MIA will provide further support for an animal model of SZ with high construct, face and predictive reliability. By accomplishing these aims the NHP core will contribute important new insights into the effects of MIA and the mechanisms by which it may contribute to the pathophysiology of SZ. If successful this will lead to the development of novel targets for the development of diagnostic biomarkers and innovative treatments for SZ and other neurodevelopmental disorders.