Continuous and interval training attenuate encephalomyelitis by separate immunomodulatory mechanisms

Goldberg, Yehuda; Fainstein, Nina; Zaychik, Yifat; Hamdi, Liel; Segal, Shir; Nabat, Hanan; Touloumi, Olga; Zoidou, Sofia; Grigoriadis, Nikolaos; Hoffman, Jay R.; Katz, Abram; Ben‐Hur, Tamir; Einstein, Ofira

doi:10.1002/acn3.51267

Cited by 11 publications

(32 citation statements)

References 32 publications

(50 reference statements)

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“…The PLP 139-151 transfer EAE model in mice was utilized as previously described. [2][3][4]17 To assess the modulatory effects of ET on systemic autoimmunity, we examined in vivo and in vitro the encephalitogenicity of lymph nodes cells (LNCs) from mice that underwent the HICT program prior to proteolipid (PLP) immunization, compared with LNCs from sedentary (SED) mice (Fig. 1A).…”

Section: Experimental Designmentioning

confidence: 99%

“…Healthy mice underwent 6-wks of HICT treadmill running, including pre-and post-training performance tests on a 5-lane treadmill designed for mice (Panlab Harvard Apparatus, USA) as previously described. 3,4,17…”

Section: Treadmill Exercise Trainingmentioning

confidence: 99%

“…The PLP 139-151 transfer EAE model was utilized as previously described. [2][3][4]17 HICT (HICT-EAE, n = 8) and SED (SED-EAE, n = 12) mice by transfer of encephalitogenic cells obtained from PLP-immunized donor mice (Fig. 1B).…”

Section: Transfer Experimental Autoimmune Encephalomyelitis (Eae)mentioning

confidence: 99%

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Exercise training alters autoimmune cell invasion into the brain in autoimmune encephalomyelitis

Hamdi

Nabat

Goldberg

et al. 2022

Ann Clin Transl Neurol

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Background The mechanisms by which exercise training (ET) elicits beneficial effects on the systemic immune system and the central nervous system (CNS) in autoimmune neuroinflammation are not fully understood. Objectives To investigate (1) the systemic effects of high‐intensity continuous training (HICT) on the migratory potential of autoimmune cells; (2) the direct effects of HICT on blood–brain‐barrier (BBB) properties. Methods Healthy mice were subjected to high‐intensity continuous training (HICT) by treadmill running. The proteolipid protein (PLP) transfer EAE model was utilized to examine the immunomodulatory effects of training, where PLP‐reactive lymph‐node cells (LNCs) from HICT and sedentary donor mice were analyzed in vitro and transferred to naïve recipients that developed EAE. To examine neuroprotection, encephalitogenic LNCs from donor mice were transferred into HICT or sedentary recipient mice and the BBB was analyzed. Results Transfer of PLP‐reactive LNCs obtained from HICT donor mice attenuated EAE severity and inflammation in recipient mice. HICT markedly inhibited very late antigen (VLA)‐4 and lymphocyte function‐associated antigen (LFA)‐1 expression in LNCs. Transfer of encephalitogenic LNCs into HICT recipients resulted in milder EAE and attenuated CNS inflammation. HICT reduced BBB permeability and the expression of intercellular adhesion molecule (ICAM)‐1 and vascular cell adhesion molecule (VCAM)‐1 in CNS blood vessels. Interpretation HICT attenuates EAE development by both immunomodulatory and neuroprotective effects. The reduction in destructive CNS inflammation in EAE is attributed to systemic inhibition of autoreactive cell migratory potential, as well as reduction in BBB permeability, which are associated with reduced VLA‐4/VCAM‐1 and LFA‐1/ICAM‐1 interactions.

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Section: Experimental Designmentioning

confidence: 99%

Section: Treadmill Exercise Trainingmentioning

confidence: 99%

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Exercise training alters autoimmune cell invasion into the brain in autoimmune encephalomyelitis

Hamdi

Nabat

Goldberg

et al. 2022

Ann Clin Transl Neurol

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“…In addition, previous studies also investigated the effect of intermittent exercise on immune function. Interval training could modulate autoimmunity by decreasing the polarization of T cells into deleterious Th1 and Th17 cells ( Goldberg et al, 2021 ). Ten weeks of low-volume, high-intensity interval exercise could improve neutrophil and monocyte function and enhance innate immune system in sedentary adults ( Bartlett et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Amelioration of Ambient Particulate Matter (PM2.5)-Induced Lung Injury in Rats by Aerobic Exercise Training

Qin

Fan

et al. 2021

Front. Physiol.

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Ambient particulate matter (PM2.5), as an inflammation-inducing factor, increases the prevalence of lung injury. The aim of this study was to examine the protective effect and mechanism of aerobic exercise on PM2.5 exposure-induced lung injury. Forty Wistar rats were randomly divided into four groups: sedentary+PM2.5 exposure, exercise+PM2.5 exposure, sedentary, and exercise groups. All rats in the exercise-related groups underwent 8-week aerobic interval treadmill training (5daysweek−1, 1hday−1). PM-exposed rats were exposed to ambient PM2.5 (6h day−1) for 3weeks after the 8-week exercise intervention. Then, ventilation function, histopathological changes, and inflammation responses of pulmonary tissue were examined. Results showed that PM2.5 exposure induced lung injury as manifested by decreased pulmonary function, abnormal histopathological changes, and increased pro-inflammatory cytokine levels (tumor necrosis factor-α and Interleukin-1α). Aerobic exercise alleviated the airway obstruction, reduced respiratory muscle strength, bronchial mucosal exfoliation, ultrastructure damage, and inflammatory responses induced by PM2.5 in exercise-related groups. The benefits of exercise were related with the downregulation of p38-mitogen-activated protein kinase (MAPK), and the subsequent inhibition of the pathways of the cyclooxygenase 2 (COX-2) product, prostaglandin E2 (PGE2). Thus, pre-exercise training may be an effective way to protect against PM2.5-induced lung inflammatory injury in rats.

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“…Other established measures are the Expanded Disability Status Scale (EDSS), the annualized relapse rate, and the Multiple Sclerosis Functional Composite (MSFC) [10]. Preclinical evidence from animal models of experimental MS supports the beneficial exercise-induced effects on disease-specific clinical measures such as the myelination status, axonal integrity, disease onset and disease progression [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Fitness, physical activity, and exercise in multiple sclerosis: a systematic review on current evidence for interactions with disease activity and progression

et al. 2022

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Background A moderate to high level of physical activity, including regular exercise, represents an established behavioral and rehabilitative approach for persons with multiple sclerosis (pwMS). Although being increasingly proposed to limit disease activity and progression, high-quality evidence is lacking. Objective The objective of the study is to provide valuable information for MS clinicians and researchers by systematically evaluating the current state of evidence (i) whether exercise interventions affect established clinical measures of disease activity and progression in pwMS (i.e., EDSS, relapse rate, lesion load, brain volume, MSFC) and (ii) how the physical activity and fitness level interact with these measures. Methods Literature search was conducted in MEDLINE, EMBASE, CINAHL, and SPORTDiscus. Evaluation of evidence quality was done based on standards published by The American Academy of Neurology. Results It is likely that exercise improves the MSFC score, whereas the EDSS score, lesion load, and brain volume are likely to remain unchanged over the intervention period. It is possible that exercise decreases the relapse rate. Results from cross-sectional studies indicate beneficial effects of a high physical activity or fitness level on clinical measures which, however, is not corroborated by high evidence quality. Conclusions A (supportive) disease-modifying effect of exercise in pwMS cannot be concluded. The rather low evidence quality of existing RCTs underlines the need to conduct more well-designed studies assessing different measures of disease activity or progression as primary end points. A major limitation is the short intervention duration of existing studies which limits meaningful exercise-induced effects on most disability measures. Findings from cross-sectional studies are difficult to contextualize regarding clinical importance due to their solely associative character and low evidence quality. PROSPERO registration number CRD42020188774.

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Continuous and interval training attenuate encephalomyelitis by separate immunomodulatory mechanisms

Cited by 11 publications

References 32 publications

Exercise training alters autoimmune cell invasion into the brain in autoimmune encephalomyelitis

Exercise training alters autoimmune cell invasion into the brain in autoimmune encephalomyelitis

Amelioration of Ambient Particulate Matter (PM2.5)-Induced Lung Injury in Rats by Aerobic Exercise Training

Fitness, physical activity, and exercise in multiple sclerosis: a systematic review on current evidence for interactions with disease activity and progression

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