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

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.

Direct Effects of Vitamin D Supplementation on Ultramarathon-Induced Changes in Kynurenine Metabolism

“…In vitamin-D-supplemented athletes, the decrease in serum TRP levels was more pronounced that that in the control group ( Figure 2 ), but the increase in the levels of TRP metabolites KYNA, XANA, QA, and PA was blunted compared to that in the control group ( Figure 3 ). An increase in circulating KYNA levels and a decrease in circulating TRP and KYN levels following acute endurance exercise have been reported in several studies [ 17 , 21 , 22 ]. This could be explained by the observation that endurance training induces the expression of KATs [ 23 ].…”

Brain Versus Blood: A Systematic Review on the Concordance Between Peripheral and Central Kynurenine Pathway Measures in Psychiatric Disorders

“…It is to be considered that central and peripheral aberrations may reflect different processes in the human body. Under physiological circumstances for example, intense physical exercise causes transient changes in the KP both in the periphery and centrally ( 61 , 161 , 162 ). KP metabolization in tissue macrophages, PBMCs and other immune cells contribute substantially to peripheral concentrations, whereas central levels of downstream metabolites are mostly determined by the lower enzymatic activity in astrocytes and microglia.…”

“…At baseline, PICO levels were strongly correlated between plasma and CSF (r=.93; n=27; p<.0001), whereas a weak correlation was seen for the other kynurenine metabolites. After exercise, however, discordance ensued for KYN (r=-.22; NS), QUINO (r=-.09; NS) and KYNA (r=-.05; NS) ( 61 ).…”

Vitamin C and E Treatment Blocks Changes in Kynurenine Metabolism Triggered by Three Weeks of Sprint Interval Training in Recreationally Active Elderly Humans

“…KP metabolites show large variations between individuals at rest and over time in connection with exercise [ 36 , 37 ]; individual data of KP metabolites in association with the first SIT session in the placebo group have been published [ 36 ]. Here we focused on KP metabolite levels under resting conditions and to get robust values, we use the mean of measurements preformed in each individual before and 24 h after SIT sessions in the untrained and trained state, respectively.…”