Plasma brain-derived neurotrophic factor (BDNF) and sphingosine-1-phosphat (S1P) are NOT the main mediators of neuroprotection induced by resistance training in persons with multiple sclerosis-A randomized controlled trial

Resistance training (RT) has been shown to elicit neuroprotective effects in persons with multiple sclerosis (pwMS). Brain-derived neurotrophic factor (BDNF) and Sphingosine-1-phosphat (S1P) have been put forward as potent mediators of the neuroprotective effects induced by RT. However, while increases have been shown in acute and chronic circulating BDNF levels in pwMS following aerobic exercise alone or in combination with other exercise regimes, no studies have examined this in response to RT. As a novel 'proof-of-concept' approach, we therefore examined the effects of 24 weeks of RT on acute and chronic circulating BDNF and S1P levels in the same pwMS whom our group had previously observed RT-induced neuroprotective effects in (i.e. increased cortical thickness and preservation of whole brain volume). A total of n = 30 relapsing-remitting pwMS were randomized into a training group (TG: 24 weeks of progressive high intensity resistance training, 2 sessions per week; n = 16, age 44[40:51] years, EDSS score 3.0[2.0:3.5] (median[IQR]) or a control group (CG: 24 weeks of habitual lifestyle; n = 14, age 45[37:47] years, EDSS score 3.0[2.5:3.5]). Plasma levels of BDNF and S1P were assessed by ELISA kits before and after the 24-week intervention period. No within- or between group changes were observed in acute or chronic circulating levels of BDNF. A substantial proportion of the participants had S1P levels below the detection limit, yet no within- or between changes were observed in chronic S1P plasma levels in the remaining samples. Thus, the present findings do not support that circulating plasma BDNF or S1P levels are the main mediators of the neuroprotective effects previously reported in the same group of pwMS.