Extracellular vesicle microRNA in neurodevelopmental models of cognitive deficit

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Project Summary Cognition is a critical and complex higher brain function that controls behavioral outcomes. Several regions in the brain, including the prefrontal cortex and hippocampus, are involved in guiding key cognitive processes. Altered functioning in these brain areas lead to cognitive deficits which are core features in psychiatric disorders such as autism, schizophrenia and depression. Data from animal and human studies indicate that the prenatal environment plays a significant role in shaping neurocognitive development in offspring. Early life stress or low childhood socioeconomic status is associated with impaired cognitive functioning in adulthood. Studies also show that altered prenatal or postnatal nutrition (including under- /over-nutrition and nutritional imbalance) leads to cognitive deficits in adolescence and adulthood. Thus, what may appear to be distinct perturbations during gestation, i.e. maternal stress or altered maternal nutrition, can result in the same behavioral outcome in adolescent and adult offspring, i.e. cognitive deficits. The developmental mechanisms responsible for impaired cognitive function are not clear. Studies in humans and animal models have suggested the involvement of the neuroendocrine and immune systems in altering offspring brain development under conditions of prenatal stress or altered maternal nutrition and metabolic state during gestation. The finding that extracellular RNA (exRNA) molecules circulate, enter distant cells and alter their phenotype has transformed our notions of intercellular communication and opened new avenues of investigation for pathogenesis and biomarker studies. This proposal will utilize two animal models to determine whether exRNAs may be a route through which the early life environment affects brain development and cognitive performance. In addition, because exRNAs are present in circulating blood, we have the potential to identify peripheral biomarkers for assessing the trajectory of brain development. Such non-invasive biomarkers would have great value in both the clinic and the laboratory.