The Functional Development of Hunger Neurons in Prader-Willi Syndrome

Funding Summary

AgRP ('hunger') neurons are found in the hypothalamus and control feeding, metabolism and compulsive behaviors. There is evidence that AgRP neurons may be overactive during development in PWS, which might lead to some of the characteristics of PWS. In this project, Dr. Dietrich will use a cutting edge technology developed in his lab to evaluate AgRP neurons in a mouse model of PWS in order to determine if the neurons are in fact overactive throughout development and across the lifespan of these PWS mice. This project will better define the altered brain circuits responsible for some of the most challenging issues in PWS, with the goal of establishing new modes of therapies.

 

Theresa Strong, Director of Research Programs, shares details on this project in this short video clip.

 

 

 Watch the full webinar describing the 8 research projects funded in this grant cycle here. 


 

Lay Abstract

Prader-Willi Syndrome (PWS) is a disorder that presents both metabolic and behavioral symptoms. PWS is caused by the loss of several genes in the human chromosome 15. The similarity between the PWS genes in humans and mice make the latter an attractive model to study the different aspects of this syndrome. PWS has been related to an altered function of a region in the mammalian brain, called hypothalamus. The hypothalamus is responsible for controlling essential functions, such as sleep, energy balance, and fertility.

Our group has been working on a specific population of neural cells in the mammalian hypothalamus, named Agrp neurons. Agrp neurons control multiple physiological functions, including adiposity, feeding, and compulsive behaviors. In preliminary studies, we found PWS related genes are enriched in Agrp neurons, mainly Magel2. Additionally, others described the gene expression profile of post-mortem samples of the hypothalamus of PWS subjects as resembling an overactivation of Agrp neurons. Based on this strong preliminary evidence, in this project we hypothesize Agrp neurons are overactive during the development of PWS subjects, contributing to clinical aspects of this syndrome. We will use a mouse model deficient in Magel2 to test this assumption, applying novel techniques that we have developed in our laboratory. For the first time, this study will evaluate in detail the function of a neuron population from breastfeeding to adulthood in an animal model of PWS, shedding new light on the pathophysiology of PWS.

Funded Year:

2019

Awarded to:

Marcelo Dietrich Ph.D

Amount:

$107,999

Institution:

Yale University

Researcher:

Marcelo Dietrich Ph.D

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