Regulatory role of cytokines on etiology of depression in animal models: their biological mechanisms and clinical implication with physical exercise

It has been known that chronic psychological or physical stress elicits depressive behaviors (learned helplessness, anhedonia, anxiety, etc.) and also activates to release proinflammatory cytokines in the brain. Especially, postmenopausal women under stress condition exacerbates neuroimmune systems and mood disorder. Repeated restraint stress in the ovariectomized female rats poses an immune challenge which was capable of inducing depressive-like behaviors, promoting exaggerated corticosterone responses and changing the proinflammatory cytokine expression such as interleukin (IL)-1β in the brain. Also, anti-inflammatory cytokines including IL-4 are known to regulate inflammation caused by immune response or stress challenge. Furthermore, some studies reported that physical activity can reduce stress hormones and improve personal immunity. Physical exercise has been shown to be associated with decreased symptoms of depression and anxiety, and with improved physical health, immunological function, and psychological well-being. This paper aims to discuss an overview of how stress shapes neuroimmune response and diverse roles of cytokines in animals models, acting on depressive-like behavioral changes; some beneficial aspects of exercise on stress-related disorders are addressed.