Differential effects on blood and cerebrospinal fluid immune protein markers and kynurenine pathway metabolites from aerobic physical exercise in healthy subjects

Josef Isung,Jesse Huang,Fredrik Piehl,Lilly Schwieler,Mathias Granqvist,Ada Trepci,Jussi Jokinen,Sophie Erhardt,Marie Kierkegaard

doi:10.1038/s41598-021-81306-4

Josef Isung, Jesse Huang + Show 7 more

Open Access

https://doi.org/10.1038/s41598-021-81306-4

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Abstract

Mounting evidence shows that physical exercise modulates systemic inflammation. However, its effect on cerebrospinal fluid (CSF) immune-marker profiles in man are largely unknown. We here report a study on healthy subjects (n = 27, males = 12, mean age 28.7, range 22–52) allocated to either an acute exercise setting over four consecutive days, or a training intervention over 4 weeks. Paired plasma and CSF samples collected at baseline, after 7 days of exercise abstention, and the day after completion of the exercise interventions, were analyzed for protein inflammation markers using a multiplex proximity extension assay and neurotransmitters and kynurenine pathway (KP) metabolites using liquid chromatography, respectively. Routine cell counts, and albumin, immunoglobulin G and neurofilament light chain concentrations in CSF remained unchanged in both paradigms, while several inflammatory proteins became upregulated after acute exercise. However, only changes in three CSF (vascular endothelial growth factor-A, interleukin-7 and matrix metalloproteinase-10) and 12 plasma proteins reached significance levels after adjustment for multiple comparisons and exclusion of less stable proteins. Similarly, KP metabolites only changed among participants after acute exercise, while neurotransmitter levels, except for increased CSF serine, remained stable. Both in plasma and CSF changes in KP metabolites and inflammatory proteins correlated, suggesting that these processes are functionally linked. These findings suggest that acute aerobic physical exercise affects immune markers and KP metabolites systemically and in the CSF.

Highlights

Mounting evidence shows that physical exercise modulates systemic inflammation
In the analysis of both baseline and post-exercise cerebrospinal fluid (CSF) from this individual, the coefficient of variation in the detection of duplicates for picolinic acid (PIC) was more than 10% and, the samples from this individual were excluded from the statistical analyses
To date data on the effect of physical exercise on immune protein marker and kynurenine pathway (KP) metabolite profiles assessed with paired sampling in blood and CSF in healthy subjects are lacking

Summary

Introduction

Mounting evidence shows that physical exercise modulates systemic inflammation. its effect on cerebrospinal fluid (CSF) immune-marker profiles in man are largely unknown. The KP involves a number of downstream metabolites of tryptophan (TRP), several of which are neuroactive through agonism or antagonism at classical neurotransmitter receptors known to be associated with mood disorders, such as the N-methyl-d-aspartate (NMDA) receptor[10] This provides a possible molecular background to effects on neuronal activation patterns that has been described in association with physical exercise, sometimes referred to as flow[11]. The two main objectives of the study were to assess the dynamic variability of immune markers as a consequence of physical exercise both in blood and CSF to shed light on molecular pathways affected by exercise and to address the potential of differences in exercise habits as a bias in biomarker studies comparing clinical populations compared to healthy controls

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