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.
