Activity-Based Anorexia Alters the Expression of BDNF Transcripts in the Mesocorticolimbic Reward Circuit

• Published in: PloS one 2016-11, Vol.11 (11), p.e0166756-e0166756
• Main Authors: Ho, Emily V, Klenotich, Stephanie J, McMurray, Matthew S, Dulawa, Stephanie C
• Format: Article
• Language: English
• Subjects: Addictions; Addictive behaviors; Adhesion tests; Analysis; Animal models; Animals; Anorexia; Anorexia - etiology; Anorexia - physiopathology; Anorexia nervosa; Appetitive behavior; Behavior, Animal; Biology and Life Sciences; Body weight; Body weight loss; Brain; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - genetics; Cell adhesion; Cell adhesion molecules; Cocaine; Disease Models, Animal; Eating disorders; Feeding; Female; Food; Gene Expression; Gene Expression Regulation; Hyperactivity; Hypophagia; Kinases; Laboratory animals; Medical imaging; Medicine and Health Sciences; Mice; Motor Activity; Neural plasticity; Neurobiology; Neuroplasticity; Nucleus accumbens; Physical Exertion; Prefrontal cortex; Psychiatry; Reinforcement; Research and Analysis Methods; Reward; RNA; Rodents; Transcription; Ventral tegmentum; Weight loss maintenance; Wheel running
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0166756

Anorexia nervosa (AN) is a complex eating disorder with severe dysregulation of appetitive behavior. The activity-based anorexia (ABA) paradigm is an animal model in which rodents exposed to both running wheels and scheduled feeding develop aspects of AN including paradoxical hypophagia, dramatic weight loss, and hyperactivity, while animals exposed to only one condition maintain normal body weight. Brain-derived neurotrophic factor (BDNF), an activity-dependent modulator of neuronal plasticity, is reduced in the serum of AN patients, and is a known regulator of feeding and weight maintenance. We assessed the effects of scheduled feeding, running wheel access, or both on the expression of BDNF transcripts within the mesocorticolimbic pathway. We also assessed the expression of neuronal cell adhesion molecule 1 (NCAM1) to explore the specificity of effects on BDNF within the mesocorticolimbic pathway. Scheduled feeding increased the levels of both transcripts in the hippocampus (HPC), increased NCAM1 mRNA expression in the ventral tegmental area (VTA), and decreased BDNF mRNA levels in the medial prefrontal cortex (mPFC). In addition, wheel running increased BDNF mRNA expression in the VTA. No changes in either transcript were observed in the nucleus accumbens (NAc). Furthermore, no changes in either transcript were induced by the combined scheduled feeding and wheel access condition. These data indicate that scheduled feeding or wheel running alter BDNF and NCAM1 expression levels in specific regions of the mesocorticolimbic pathway. These findings contribute to our current knowledge of the molecular alterations induced by ABA and may help elucidate possible mechanisms of AN pathology.