Development of appetite-related neural circuits in a mouse model for Prader-Willi syndrome (year 1)

Prader-Willi syndrome (PWS) is a genetic disease characterized by an insatiable appetite and a variety of behavioral dysregulations. It is known that the brain, and particularly a region of the brain called the hypothalamus, is important to regulating appetite and body weight. We also know that many key physiological processes, including appetite regulation, are established during the perinatal period — that time just prior to and soon after birth – and that hormonal conditions in the babies are key in these processes. Notably, babies with PWS display abnormally elevated levels of the gut-hormone ghrelin and we recently found in our lab that this hormone has marked effects on hypothalamic development. The goal of this research project is to determine, using a mouse model for PWS, whether the elevated levels of ghrelin observed in babies with PWS disrupt the normal development of brain circuits involved in appetite regulation. The results of these experiments promise to provide new insight into the mechanism by which alteration of the early life hormonal environment that occurs in children with PWS, leads to perturbations of neurodevelop-mental events and may result to hyperphagia and obesity in later life. The knowledge we gain from this project may also help determine therapeutic interventions to reduce metabolic and neurological problems associated with PWS.

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