Treating Depression and Depression-Like Behavior with Physical Activity: An Immune Perspective

Abstract

The increasing burden of major depressive disorder makes the search for an extended understanding of etiology, and for the development of additional treatments highly significant. Biological factors may be useful biomarkers for treatment with physical activity (PA), and neurobiological effects of PA may herald new therapeutic development in the future. This paper provides a thorough and up-to-date review of studies examining the neuroimmunomodulatory effects of PA on the brain in depression and depression-like behaviors. From a neuroimmune perspective, evidence suggests PA does enhance the beneficial and reduce the detrimental effects of the neuroimmune system. PA appears to increase the following factors: interleukin (IL)-10, IL-6 (acutely), macrophage migration inhibitory factor, central nervous system-specific autoreactive CD4+ T cells, M2 microglia, quiescent astrocytes, CX3CL1, and insulin-like growth factor-1. On the other hand, PA appears to reduce detrimental neuroimmune factors such as: Th1/Th2 balance, pro-inflammatory cytokines, C-reactive protein, M1 microglia, and reactive astrocytes. The effect of other mechanisms is unknown, such as: CD4+CD25+ T regulatory cells (T regs), CD200, chemokines, miRNA, M2-type blood-derived macrophages, and tumor necrosis factor (TNF)-α [via receptor 2 (R2)]. The beneficial effects of PA are likely to occur centrally and peripherally (e.g., in visceral fat reduction). The investigation of the neuroimmune effects of PA on depression and depression-like behavior is a rapidly developing and important field.

Physical and Immunological Aspects of Exercise in Chronic Diseases

“…Interestingly, physical activity changes the neuro-immune status in depression and depression-like behaviours. As such, during physical activity increases are noted for, IL-10, IL-6 (transiently), macrophage migration inhibitory factor, central nervous system-specific auto-reactive CD4+ T ells, M2 microglia, astrocytes, CX3CL1 and insulin-growth factor-1 [99], all of which may have beneficial neuro-immunological effects in the management of depression. However, detrimental decreases are noted for the Th1/Th2 balance, pro-inflammatory cytokines, CRP, M1 microglia and reactive astrocytes [99].…”

“…As such, during physical activity increases are noted for, IL-10, IL-6 (transiently), macrophage migration inhibitory factor, central nervous system-specific auto-reactive CD4+ T ells, M2 microglia, astrocytes, CX3CL1 and insulin-growth factor-1 [99], all of which may have beneficial neuro-immunological effects in the management of depression. However, detrimental decreases are noted for the Th1/Th2 balance, pro-inflammatory cytokines, CRP, M1 microglia and reactive astrocytes [99]. Furthermore, swimming exercise decreases depression-like behaviour by decreasing serum corticosterone, IFN-gamma, TNF-alpha, indoleamine-2,3-deoxygenase (IDO) and increasing 5-HT levels [100].…”

Pathophysiological Relationships Between Heart Failure and Depression and Anxiety

“…109 Physical activity also enhances antiinflammatory responses and reduces proinflammatory responses. 110 Currently, physical activity is recommended as safe and effective in patients with heart failure. 111 Multidisciplinary, multicomponent disease management programs for patients with heart failure were examined in 7 studies.…”

Exercise-Induced Change in Plasma IL-12p70 Is Linked to Migraine Prevention and Anxiolytic Effects in Treatment-Naïve Women: A Randomized Controlled Trial

“…Extensive literature indicates that regular moderate aerobic exercise modulates the immune system, affecting mental [1] and physical health [2-4]. A consistent line of evidence suggests an intricate exercise-dependent regulation between the stress neuroendocrine system and type 1/type 2 cytokine balance, with repercussions on pathogenic processes depending on anti- or proinflammatory actions of these cytokines [1, 2, 5].…”