Browsing by Author "Walzik, David"

The findings of this study show that acute endurance exercise activates a receptor that has been described to integrate metabolic signals into the immune system. We uncover a potential mechanistic link on how exercise modulates the immune system through the kynurenine pathway-AHR axis, potentially underlying exercise-induced benefits in various chronic diseases and of relevance for other cell types.

The kynurenine pathway of tryptophan degradation generates several metabolites such as kynurenine or kynurenic acid that serve as endogenous ligands of the aryl hydrocarbon receptor (AHR). Due to its distinct biological roles particularly modulating the immune system, the AHR is a current therapeutic target across different inflammation-related diseases. Here, we show an exercise-induced increase in AHR ligand availability on a systemic level and a kynurenine pathway activation in peripheral mononuclear blood cells (PBMCs). Concurrently, the AHR is activated in PBMCs following acute exercise, with effects being dependent on exercise intensity. In conclusion, these data indicate a novel mechanistic link how exercise modulates the immune system through the kynurenine pathway-AHR axis, potentially underlying exercise-induced benefits in various chronic diseases.

Due to distinct immuno- and neuro-modulatory properties, growing research interest focuses on exercise-induced alterations of the kynurenine (KYN) pathway in healthy and clinical populations. To date, knowledge about the impact of different acute strength exercise modalities on the KYN pathway is scarce. Therefore, we investigated the acute effects of hypertrophic (HYP) compared to maximal (MAX) strength loadings on the KYN pathway regulation.

Alterations in immunological homeostasis induced by acute exercise have been frequently reported. In view of the growing amount of repetitive exercise stimuli in competitive sports, quick recovery plays a superior role. Therefore, we examined whether aqua cycling affects cellular immunological recovery.

Exercise-induced cellular mobilization might play a role in treatment and prevention of several diseases. However, little is known about the impact of different exercise modalities on immune cell mobilization and clinical cellular inflammation markers. Therefore, the present study aimed to investigate differences between acute endurance exercise (EE) and resistance exercise (RE) on cellular immune alterations.

Background: Acute aerobic exercise leads to positive physiological adaptations within the central nervous system. These findings inspired research on potential cognitive benefits following acute aerobic exercise. The effects of acute aerobic exercise on subsequent cognitive performance, by far, have been the most researched for interference control, a subcomponent of executive function. The results of primary studies on the effects of acute aerobic exercise on subsequent interference control performance are inconsistent. Therefore, we used meta-analytic methods to pool available effect sizes, and to identify covariates that determine the magnitude of exercise-induced interference control benefits. Methods: Medline, PsycINFO, and SPORTDiscus were searched for eligible records. Hedges' g corrected standardized mean difference values (SMDs) were used for analyses. Random-effects weights were used to pool effect sizes. Moderator analyses were conducted using meta-regressions and subgroups analyses. Covariates that were here tested for moderation included parameters of the applied exercise regimen (exercise intensity and exercise duration), characteristics of examined participants (age and fitness), and methodological features of existing research (type of control group, familiarization with test procedure, type of test variable, delay between exercise cessation, and testing). Results: Fifty studies, with data from 2,366 participants, were included in qualitative and quantitative synthesis. A small, significant beneficial effect of acute aerobic exercise on time-dependent measures of interference control was revealed (k = 49, Hedges' g = -0.26, 95%CI: -34 to -0.18). Effect sizes from time-dependent measures of interference control varied widely and heterogeneity reached statistical significance (T 2 = 0.0557, I 2 = 28.8%). Moderator analyses revealed that higher exercise intensities (vigorous intensity and high-intensity interval training), also participants at younger or older age, and participants who are familiar with the testing procedure prior to the experiment, benefitted most from acute aerobic exercise. However, noticeable heterogeneity remained unexplained within specific subgroups (high-intensity interval training, preadolescent children, and active and supervised control group). Conclusion: Acute aerobic exercise improves subsequent interference control performance. However, the covariates exercise intensity, participants' age, and familiarization with testing procedure determine the magnitude of that effect. Methodological features were not found to influence the magnitude of effects. This dismisses some doubts that exercise induced benefits for interference control performance are scientific artifacts. The fact that large heterogeneity remained unexplained in some subgroups indicates the need for further research on covariates within these subgroups. It should be noted that effect sizes for all analyses were small.

B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific immunoglobulins. Exercise alters B cell counts and immunoglobulin levels, but evidence-based conclusions on potential benefits for adaptive immunity are lacking. This systematic review assessed current literatures on the impact of acute exercise and exercise training on B cells, immunoglobulins, and markers of secretory immunity in human biofluids.

The relevance of regular moderate to intense exercise for ameliorating psychomotor symptoms in persons with multiple sclerosis (pwMS) is becoming increasingly evident. Over the last two decades, emerging evidence from clinical studies and animal models indicate immune regulatory mechanisms in both periphery and the central nervous system that may underlie these beneficial effects. The integrity of the blood-brain barrier as the main structural interface between periphery and brain seems to play an important role in MS. Reducing the secretion of proteolytic matrix metalloproteinases (MMP), i.e. MMP-2, as disruptors of blood-brain barrier integrity could have profound implications for MS.

While pre-post differences in immune cell mobilization after acute aerobic exercise are well investigated, less is known about when and to what extent immune cells are mobilized during acute aerobic exercise. This experimental trial aimed to investigate the detailed kinetics of circulating immune cells in twelve healthy adults (n=6 females) who completed a 40-min aerobic exercise bout at 60% of the participants' V̇O2peak on a bicycle ergometer. Cellular inflammation markers and sex-dependent differences in circulating immune cells were analyzed. Blood samples were taken immediately before, after warm-up, during exercise after 5 min, 10 min, 15 min, 30 min, 40 min (cessation), and 60 min post exercise. Significant increases in leukocytes (p<0.001), lymphocytes (p<0.001), neutrophils (p=0.003) and platelets (p=0.047) can be observed after five min of exercise. The cellular inflammation markers show significant alterations only post exercise. Significant sex differences were observed for neutrophils (p=0.049) and neutrophil-to-lymphocyte ratio (p=0.007) one hour post exercise. These results indicate that i) leukocytes are already mobilized after 5 min of moderate-to-vigorous aerobic exercise, ii) the magnitude of exercise induced leukocyte mobilization is dependent on exercise duration, iii) integrative cellular inflammation markers are only altered after exercise cessation, and iv) the observed effects might be sex-dependent.

Abstract Despite substantial evidence emphasizing the pleiotropic benefits of exercise for the prevention and treatment of various diseases, the underlying biological mechanisms have not been fully elucidated. Several exercise benefits have been attributed to signaling molecules that are released in response to exercise by different tissues such as skeletal muscle, cardiac muscle, adipose, and liver tissue. These signaling molecules, which are collectively termed exerkines , form a heterogenous group of bioactive substances, mediating inter-organ crosstalk as well as structural and functional tissue adaption. Numerous scientific endeavors have focused on identifying and characterizing new biological mediators with such properties. Additionally, some investigations have focused on the molecular targets of exerkines and the cellular signaling cascades that trigger adaption processes. A detailed understanding of the tissue-specific downstream effects of exerkines is crucial to harness the health-related benefits mediated by exercise and improve targeted exercise programs in health and disease. Herein, we review the current in vivo evidence on exerkine-induced signal transduction across multiple target tissues and highlight the preventive and therapeutic value of exerkine signaling in various diseases. By emphasizing different aspects of exerkine research, we provide a comprehensive overview of (i) the molecular underpinnings of exerkine secretion, (ii) the receptor-dependent and receptor-independent signaling cascades mediating tissue adaption, and (iii) the clinical implications of these mechanisms in disease prevention and treatment.

Background: A noticeable proportion of adolescents with depression do not respond to guideline recommended treatment options. This systematic review and meta-analysis investigated the effectiveness of physical activity interventions as an alternative or complementary treatment for adolescents (12-18 years) with depression. The characteristics of the physical activity treatment that were most effective in reducing symptoms in adolescents with depression and the impact of methodological shortcomings in the existing research were also examined. Methods: Medline, PsycINFO, SPORTDiscus, ProQuest, and CENTRAL were searched for eligible records. Effect size estimates were pooled based on the application of a random-effects model. Potential moderation by physical activity characteristics (i.e., intensity, type, context, and time frame) and methodological features (i.e., type of control group and diagnostic tool to identify depression at baseline) was investigated by means of subgroup analyses and meta-regressions. The certainty of evidence was assessed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The primary outcome was the antidepressant effect of physical activity at postintervention measurement time point. As secondary outcomes, the sustainability of effects after the end of physical activity treatment and the acceptability of physical activity treatments were assessed. Overall, 10 studies were included in the qualitative synthesis and 9 studies involving 431 patients were included in the quantitative synthesis. Results: A moderate, significant antidepressant effect of physical activity was found (Hedges' g = -0.47, 95% CI = -0.71 to -0.24). Heterogeneity was small (T2 = 0.0313, I 2 = 27%, p = 0.18). However, the certainty of evidence was downgraded to low because the included studies contained serious methodological limitations. Moderator analyses revealed that session intensity significantly moderated the antidepressant effect of physical activity. Moreover, noticeably smaller effect sizes were found in studies that used non-physical activity sham treatments as control treatments (e.g., playing board games), compared to studies that used no control group treatments. Only three studies assessed the sustainability of effects after the end of physical activity treatment. The results suggest that the antidepressant effects further increase after the end of physical activity interventions. There was no significant difference in dropout risk between the physical activity and control groups. Conclusions: This review suggests that physical activity is effective in treating depression in adolescents. Physical activity sessions should be at least moderately intense [rate of perceived exertion (RPE) between 11 and 13] to be effective. Furthermore, our results suggest that physical activity treatments are well accepted. However, the low methodological quality in included studies might have led to effect overestimation. Therefore, more studies with higher methodological quality are needed to confirm the recommendation for physical activity treatments in adolescents with depression.

Nicotinamide adenine dinucleotide (NAD+ ) is an evolutionarily highly conserved coenzyme with multi-faceted cell functions, including energy metabolism, molecular signaling processes, epigenetic regulation, and DNA repair. Since the discovery that lower NAD+ levels are a shared characteristic of various diseases and aging per se, several NAD+ -boosting strategies have emerged. Other than pharmacological and nutritional approaches, exercise is thought to restore NAD+ homeostasis through metabolic adaption to chronically recurring states of increased energy demand. In this review we discuss the impact of acute exercise and exercise training on tissue-specific NAD+ metabolism of rodents and humans to highlight the potential value as NAD+ -boosting strategy. By interconnecting results from different investigations, we aim to draw attention to tissue-specific alterations in NAD+ metabolism and the associated implications for whole-body NAD+ homeostasis. Acute exercise led to profound alterations of intracellular NAD+ metabolism in various investigations, with the magnitude and direction of changes being strongly dependent on the applied exercise modality, cell type, and investigated animal model or human population. Exercise training elevated NAD+ levels and NAD+ metabolism enzymes in various tissues. Based on these results, we discuss molecular mechanisms that might connect acute exercise-induced disruptions of NAD+ /NADH homeostasis to chronic exercise adaptions in NAD+ metabolism. Taking this hypothesis-driven approach, we hope to inspire future research on the molecular mechanisms of exercise as NAD+ -modifying lifestyle intervention, thereby elucidating the potential therapeutic value in NAD+ -related pathologies.