Metabolic miR-137 Effects Contribute to Neuronal Signaling

Modified Project Summary/Abstract Section Here, we focus on the microRNA, miR-137, which is enriched in the brain and strongly linked to Schizophrenia (SCZ) and Bipolar Disorder (BP) with genome-wide significance. In addition to neuropsychiatric symptoms, SCZ and BP patients suffer from ~10-15 year reduction in life expectancy and this early mortality is due to a high prevalence of obesity, Type II Diabetes (T2D), hyperglycemia, elevated cholesterol and triglycerides, high blood pressure, and irregularities in insulin signaling. Our overarching hypothesis is that miR-137 drives both neuronal and metabolic dysfunction, and that metabolic dysfunction contributes to disease susceptibility/progression. Drosophila has served as a powerful genetic model system for studying both neuronal signaling as well as obesity and diabetes because organs, signaling pathways and proteins, as well as neuronal ion channels/receptors are highly conserved across species, and many disease-associated genes are conserved between Drosophila and humans. Using Drosophila as an experimental system, we have found that miR-137 regulates both metabolic and neuronal function. In this application, we propose studies to further our understanding of how miR-137 affects metabolism to ultimately affect neuronal signaling.