2015 Theses Doctoral

Interactions between the BDNF (Val66Met) variant and stress as a model of susceptibility to Anorexia Nervosa

Madra, Moneek

Anorexia nervosa (AN) is a complex disease involving interactions between genetic, environmental, and psychological factors. In order to identify new treatments for AN, we created a novel mouse model of AN. We elicited aphagic behavior in mice by combining risk factors of AN - adolescent females, predisposition to anxiety, the brain-derived neurotrophic factor (BDNF)-Val66Met variant, social stress and caloric restriction. We demonstrated that abnormal feeding behavior in our model was associated with increases in central AVP tone. In further investigation of this aphagic behavior we characterized the involvement of maternal and paternal factors in our model. We observed that adolescent handling reversed the AVP mediated molecular phenotype, but did not change neuroendocrine or neuronal stress markers. We have identified the role of multiple factors in the development of abnormal feeding behaviors and focused mechanistic investigations on central AVP components. By doing so, we have identified the AVP receptor, AVPR1A as a potential target for therapeutic interventions.