The Functional Development of Hunger Neurons in Prader-Willi syndrome (Year 2)

Funding Summary

Dr. Dietrich’s lab has been working on “hunger” neurons, Agrp neurons, that are contained in the hypothalamus in animal brains. They have found that PWS-related genes, particularly Magel2, are enriched in Agrp neurons. In the second year of funding for this study, they will use a mouse model that is missing Magel2 to look at the function of the Agrp neurons from breastfeeding to adulthood, which will help identify the pathophysiology of PWS.

 

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

 

Watch the full webinar describing all 9 research projects funded in this grant cycle here

 

Lay Abstract

Prader-Willi Syndrome (PWS) is a disorder that presents both metabolic and behavior 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 and compulsive behaviors. In preliminary studies, we found PWS related genes are enriched in Agrp neurons, mainly Magel2. Studying post-mortem brain samples from PWS subjects, others have found that gene expression in the hypothalamus is best explained by overactivation of Agrp neurons. In this project, we hypothesize Agrp neurons are overactive in PWS during development, 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. 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:

2020

Awarded to:

Marcelo Dietrich, PhD

Amount:

$108,000

Institution:

Yale University

Researcher:

Marcelo Dietrich, PhD

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