Elsevier

Brain Research Bulletin

Volume 125, July 2016, Pages 19-29
Brain Research Bulletin

Review
Physical activity and exercise attenuate neuroinflammation in neurological diseases

https://doi.org/10.1016/j.brainresbull.2016.03.012Get rights and content

Highlights

  • A physically active lifestyle reduces the risk of developing brain diseases.

  • Exercise and physical activity have whole body anti-inflammatory effects.

  • Exercise may be neuroprotective due to a reduction in neuroinflammation.

  • Exercise intervention can reduce neuroinflammation in brain disease and improve prognosis.

Abstract

Major depressive disorder (MDD), schizophrenia (SCH), Alzheimer’s disease (AD), and Parkinson’s disease (PD) are devastating neurological disorders, which increasingly contribute to global morbidity and mortality. Although the pathogenic mechanisms of these conditions are quite diverse, chronic neuroinflammation is one underlying feature shared by all these diseases. Even though the specific root causes of these diseases remain to be identified, evidence indicates that the observed neuroinflammation is initiated by unique pathological features associated with each specific disease. If the initial acute inflammation is not resolved, a chronic neuroinflammatory state develops and ultimately contributes to disease progression. Chronic neuroinflammation is characterized by adverse and non-specific activation of glial cells, which can lead to collateral damage of nearby neurons and other glia. This misdirected neuroinflammatory response is hypothesized to contribute to neuropathology in MDD, SCH, AD, and PD. Physical activity (PA), which is critical for maintenance of whole body and brain health, may also beneficially modify neuroimmune responses. Since PA has neuroimmune-modifying properties, and the common underlying feature of MDD, SCH, AD, and PD is chronic neuroinflammation, we hypothesize that PA could minimize brain diseases by modifying glia-mediated neuroinflammation. This review highlights current evidence supporting the disease-altering potential of PA and exercise through modifications of neuroimmune responses, specifically in MDD, SCH, AD and PD.

Introduction

It is universally accepted that physical activity (PA) is crucial for maintaining a healthy body. The whole-body benefits of both PA (a consistent routine of body movement that burns calories) and exercise (a subcategory of PA that includes planned, structured and repetitive activity aimed towards enhanced muscular tone or endurance abilities) are well known (Centers for Disease Control and Prevention, 2015). Although PA and exercise are defined differently, their outcomes frequently overlap, often achieving a similar overall effect. The effects of PA and exercise can include increased cardiovascular endurance and capacity, enhanced muscular tone, increased muscular strength, improved metabolism, and decreased adiposity (Bergman, 2013, Egan and Zierath, 2013, Fiuza-Luces et al., 2013, Peixoto et al., 2015, Stewart et al., 2005, Stojanovic et al., 2012). PA also has beneficial effects in the brain such as improved mood and mental health, as well as enhanced memory and cognitive abilities (Moore et al., 2014, Roig et al., 2013). Recent evidence shows that in addition to modifying cardiovascular, muscular and endocrine systems, both acute and chronic exercise have immune-modifying properties, which can lead to an overall whole-body anti-inflammatory effect (Flynn and McFarlin, 2006, Gleeson et al., 2011, Pedersen, 2006, Stewart et al., 2005). The extent to which PA and exercise modify immune responses is just developing, with an emerging focus on the potential immune-modifying effects of exercise in the brain. The purpose of this review is to summarize the published data on the immune-modifying effects of PA in the brain. We will focus on the neuroimmune effects of PA in the central nervous system (CNS) and highlight the use of exercise as a possible therapeutic option for those suffering from major depressive disorder (MDD), schizophrenia (SCH), Alzheimer’s disease (AD) and Parkinson’s disease (PD), since each of these pathologies has a neuroinflammatory component.

Section snippets

Anti-inflammatory effects of physical activity and exercise in the periphery

The innate immune system is the body’s major defense system, which is necessary for fighting exogenous pathogens and eliminating any resulting infections. However, the innate immune system can also be activated in the absence of infection in response to endogenous danger signals, such as necrotic cellular debris and damage-associated molecular patterns (DAMPs) (Dheen et al., 2007). Once the immune system has recognized either exogenous or endogenous triggers, the process of inflammation works

Physical activity and exercise and the brain

The health benefits of exercise are not restricted to peripheral tissues, but extend to the CNS, as well. Several studies and supporting meta-analyses have demonstrated that exercise enhances mood in a wide demographic ranging from youth to seniors, and in healthy and diseased individuals alike (Adamson et al., 2015, Annesi and Tennant, 2012, Hoffman et al., 2010, Johnson and Castle, 2015, Powers et al., 2015). This is consistent with previous research, which has shown PA to enhance the

Neuroimmune-modifying effects of physical activity and exercise

Inflammation in the CNS involves the recruitment and activation of specialized immune cells called glia. These include microglia, the resident macrophages of the CNS that specialize in debris clearance and antigen presentation; astrocytes, which specialize in neuronal support and tissue repair; and oligodendrocyes, which insulate and support neurons (Jessen, 2004). In the presence of infection or injury, glia become activated and work together to repair the damage and restore brain homeostasis (

Summary and hypotheses

Experimental and epidemiological studies have demonstrated that living a healthy and physically active lifestyle reduces the risk (Barnes and Yaffe, 2011, Scarmeas et al., 2009, Zou et al., 2015) and severity of neurological diseases (Archer and Kostrzewa, 2015, Canning et al., 2015, Erickson et al., 2012, Eyre and Baune, 2012, Frazzitta et al., 2015, Frazzitta et al., 2014, Liu et al., 2013, Radak et al., 2007, Radak et al., 2013, Suijo et al., 2013, Uc et al., 2014, Yu et al., 2014). However,

Conclusion

Although it has been accepted for years that PA is necessary to maintain a healthy body and mind, the true scope of the benefits of PA and exercise at the cellular and molecular level has yet to emerge. Recent evidence highlights the potential for PA and exercise to reduce peripheral and CNS diseases that have an underlying element of chronic inflammation. This is particularly relevant for brain diseases such as MDD, SCH, AD and PD, which involve mechanisms that are still poorly understood,

Acknowledgements

AK is supported by grants from the Jack Brown and Family Alzheimer’s Disease Research Foundation, the Natural Science and Engineering Research Council of Canada and the University of British Columbia Okanagan Campus. JPL is supported by a Canadian Institutes of Health Research (CIHR) New Investigator Salary Award (MSH-141980).

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