Medical Student Research Fellowship for Summer 2010

Mentor: Jeffrey Zigman, MD, PhD
Department: Internal Medicine and Psychiatry
Room number: Y6.220D
Mail Code: 9077
Phone number: 214-648-6422
E-mail: jeffrey.zigman@utsouthwestern.edu
Project title: The Mechanism of Ghrelin's Antidepressant and Orexigenic Actions

Human subjects IRB approved project number (where applicable):

Animal subjects IRB approved project number (where applicable): 1149-07-01-1; 2008-0107

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)

Brief Description of Project: Ghrelin is a hormone with diverse actions, the most studied of which are its effects on body weight. Our recent work also demonstrates antidepressant-like behavioral effects of ghrelin. As such, ghrelin levels rise not only in association with hunger and fasting, thus leading to stimulation of food intake and conservation of energy stores, but also upon chronic stress. These elevations with stress seem to minimize the depression-like behaviors normally associated with stress, as acute peripheral infusions of ghrelin into wild-type mice induce antidepressant-like behaviors, and as mice lacking ghrelin receptors (growth hormone secretagogue receptor; GHSR) demonstrate even more depression-like behaviors than wild-type mice. Ghrelin rises also mediate the antidepressant-like effects of prolonged caloric restriction. The current project aims to further explore the mechanism by which ghrelin promotes eating and antidepressant behaviors. We will employ unique genetically-manipulated mouse models in which GHSR expression can be site-selectively targeted to or deleted from specific brain regions (ventral tegmental area and hippocampus) as well as CNS site-specific ghrelin microinjection studies to determine the role of the VTA and hippocampus in ghrelin's antidepressant and orexigenic effects. We hope that these studies will uncover new pathways involved in the development of mood disorders, including the depression so closely linked to conditions with known perturbations of ghrelin physiology such as anorexia nervosa and obesity.

Previous Research Activities or Publications with Medical Students: In the two past Summers, I have had two medical students working in the lab as part of this Medical Student Research Fellowship. The first medical student is a co-author on a manuscript recently published, and was also a co-author on some related abstracts at national scientific meetings.

Perello M, Sakata I, Birnbaum S, Chuang J-C, Osborne-Lawrence S, Rovinsky SA, Woloszyn J, Yanagisawa M, Lutter M*, Zigman JM*. Ghrelin increases the rewarding value of high fat diet in an orexin-dependent manner. Biol Psych. 2009 Dec 23 Epub In press. NIHMSID #158118