Abstract:
Depression is one of the most common psychiatric disorders and a leading cause of
disability worldwide. Environmental factors, mainly stress, play an important role in
promoting this disorder by inducing changes in gene expression that are sustained by
epigenetic modifications, particularly in the hippocampal brain regions.
Transcriptional profiling of the hippocampus revealed a downregulation in the Brain-
Derived Neurotrophic Factor (Bdnf) gene expression in animal models of stress, and
this downregulation was reversed by antidepressant treatment and physical exercise.
In our study, we use a chronic social defeat paradigm, a validated model of depression
in mice, to study the antidepressant effect of the endogenous molecule lactate that is released after physical exercise. We used multiple behavioral tests including open
field, T-maze and social interaction tests to show that lactate rescues depression
phenotypes such as defeat and anxiety behavior We also report that lactate activates
independent pathways to affect two separate processes: promotion of resilience to
stress and protection from depression. Our results reveal an antidepressant-like activity
of an endogenous molecule lactate, produced after physical exercise and known to
accumulate in the hippocampal regions of the brain and illustrate a novel mechanism
that can explain the positive effects of exercise on mood disorders.
