Combinatory effect of diet and exercise on brain derived neurotrophic factor expression, cognitive function and behavioral phenotypes of psychiatric disorders. (c2017)

Abstract

Psychiatric diseases are characterized by varying forms of cognitive impairment. Human and mouse Brain Derived Neurotropic Factor (BDNF) levels are altered in psychiatric diseases, and BDNF signaling not only contributes to the pathophysiology of depression, but also is important for the therapeutic effects of antidepressants. Its involvement in the learning processes and memory formation has also been well established. BDNF levels are dramatically decreased in the adult brain in response to stress and are elevated by increased exercise. Furthermore, exercise induces beneficial responses in the brain, many of which are mediated through induction of Bdnf expression. In this work, we aim to study the effect of combining different diets with voluntary exercise on Bdnf expression and in turn on learning, memory and amelioration of depression symptoms. The overall hypothesis is that determining how exercise and different diets coordinate to induce Bdnf gene expression will identify novel therapeutic targets for depression and lifestyle adjustments that may prevent depression. We have found that combining a high protein diet with exercise has an additive effect on the induction of brain Bdnf expression. We have also identified the branched chain amino acid leucine to be a crucial amino acid involved in BDNF induction. The branch chain amino acids, leucine, isoleucine and valine had very modest effects on improvement of learning and memory. However, leucine, isoleucine and valine rescued behavioral phenotypes in a chronic social defeat mouse model and promoted resilience to stress.