Exercise-induced changes in neurotrophic factors and markers of blood-brain barrier permeability are moderated by weight status in multiple sclerosis

Abstract

Blood-brain barrier (BBB) and neurotrophic factors seemingly have an important role in multiple sclerosis pathology. Physical activity may influence blood-brain barrier function and levels of neurotrophic factors, and such effects might be moderated by body weight status. This study investigated the effect of exercise training on markers of blood-brain barrier permeability and neurotrophic factors as a function of weight status in multiple sclerosis patients. Sixty three persons with relapsing remitting multiple sclerosis who were normal weight (n: 33) or overweight (n: 33) were randomly assigned into groups of exercise (normal weight training, n: 18; overweight training group, n: 18) or no exercise (normal weight control, n: 15; overweight control group, n: 15). The intervention consisted of 8 weeks (3 days per week) of cycling undertaken at 60-70% peak power. Resting blood concentrations of s100 calcium-binding protein B (s100b) and neuron-specific enolase as BBB permeability markers, neurotrophic factors and cytokines (Interleukin-10 and tumor necrosis factor alpha) were evaluated before and after the intervention. There were significant weight, training, and interaction effects on brain-derived neurotrophic factor and platelet-derived growth factor; however, ciliary neurotrophic factor and nerve growth factor did not demonstrate any effect. Brain-derived neurotrophic factor and platelet-derived growth factor were significantly increased from pre-post in normal weight exercise. Significant weight, training, and interaction effects were found for s100b. In detail, s100b was significantly increased from pre-post in normal weight exercise. In contrast, neuron-specific enolase and cytokines did not demonstrate any effect. Generally, Exercise training may alter markers of BBB permeability and neurotrophic factor status in normal weight persons with multiple sclerosis; however, overweight participants may be more resistant to these effects of exercise.

Effects of exercise training on multiple sclerosis biomarkers of central nervous system and disease status: a systematic review of intervention studies

“…Three studies focused on BBB function markers in pwMS (Table ). Studies used peripheral circulation markers including matrix metallopeptidase (MMP)‐9 , MMP‐2 , s100 calcium‐binding protein B and neuron‐specific enolase . Results of BBB markers studies revealed a positive effect of exercise, particularly where s100 calcium‐binding protein B was investigated.…”

“…Results of BBB markers studies revealed a positive effect of exercise, particularly where s100 calcium‐binding protein B was investigated. Nine studies focused on neurotrophic factors (Table ) including brain‐derived neurotrophic factor (BDNF) , nerve growth factor , neurotrophin‐4 (one study), platelet‐derived growth factor and ciliary neurotrophic factor in pwMS. Among eight studies that investigated the effects of exercise training on BDNF, four studies reported a significant increase (see Appendix S1).…”

“…s100 calcium‐binding protein B and neuron‐specific enolase have been investigated in one previous study . In this randomized controlled trial, only s100 calcium‐binding protein B demonstrated significant change in the normal‐weight group who exercised.…”

“…In this randomized controlled trial, only s100 calcium‐binding protein B demonstrated significant change in the normal‐weight group who exercised. As exercise training is able to reduce reactive oxygen species and pro‐inflammatory cytokines , physical activity can be considered as a strategy to reduce BBB permeability and to improve integrity. A study that examined MMP‐2 and MMP‐9 as BBB indicators showed significant reductions in the serum level of MMP‐2, but not MMP‐9, after high‐intensity interval training.…”

Cultivating a healthy neuro‐immune network: A health psychology approach

“…In a study of older women, exercise and exercise combined with taurine supplementation (a common amino acid in the body that declines with age) led to reduced peripheral inflammation and increased integrity of the BBB as measured by both S100β and NSE (Chupel et al, ). Similarly, exercise led to decreases in S100β (though no changes in NSE) among normal weight patients with MS (Mokhtarzade et al, ).…”