Prader-Willi Syndrome (PWS) is a rare genetic disorder with symptoms that typically include obesity, severe appetite and impaired reproductive function. It is thought that dysfunction of the hypothalamus, a part of the brain that controls body weight and reproduction, underlies some of these symptoms. Our goal is to understand what is dysfunctional in the hypothalamus in PWS. Melanin concentrating hormone (MCH) is a chemical found only in a certain population of nerve cells within the hypothalamus. These cells, called MCH neurons, secrete MCH to signal to other cells in the brain, which in turn stimulate appetite and weight gain. MCH also suppresses the reproductive system. Therefore, intense appetite, weight gain and impaired reproduction in PWS may be explained by overactive MCH neurons. To test this idea, we will use a mouse model that shows some PWS-like symptoms. We will investigate whether MCH is more abundant in the hypothalamus and whether MCH neurons are more active in these animals. In addition, we will experimentally reduce the amount of MCH in the hypothalamus of these mice in an attempt to lessen the PWS-like symptoms. I believe it is important to investigate a potential link between MCH and PWS, given the known role of MCH in controlling body weight and reproduction. This will be the first study on MCH in a mouse model of PWS, which may bring promising results for identifying a new therapeutic target.
This project was funded by the Foundation for Prader-Willi Research Canada.