An overview of the molecular and physiological antidepressant mechanisms of physical exercise in animal models of depression.

Background: Depression is a global disease that affects the physical and mental health of people of all ages. Non-pharmacological and unconventional methods of treatment, such as regular physical exercise, have been recommended to treat depression.

Methods: Here, we briefly review the literature about the physiological and molecular mechanisms of exercise antidepressants in depressive-like behavior in animal models of depression.

Results: The main hysiological and molecular mechanisms of physical exercise in depression include blood flow changes in several areas of the brain, increase in brain serotonin synthesis, increase in antioxidant enzymes, increase in serum and brain brain-derived neuro factor (BDNF) levels, decrease in cortisol levels and reduced inflammation in peripheral and brain tissues. Physical exercise also leads to increased activation of the phosphatidylinositol-3-kinase (PI3K), PGC-1α/FNDC5/Irisin pathway, BDNF concentrations (serum and cerebral), extracellular signal-regulated kinase and cAMP-response element binding protein (mainly in neurons of the hippocampus and prefrontal cortex), which together contribute to fight or inhibit the development of depression symptoms. These molecular and physiological mechanisms work in synchrony, further enhancing their effects.

Conclusion: Physical exercise can be used as a safe and effective non-pharmacological treatment in depression.