Abstract
Brain-derived neurotrophic factor (BDNF) is an essential mediator of exercise-induced neuroplasticity. The majority of BDNF in circulation (∼99%) is stored bound to platelets. Platelet activation by exercise stimulates the release of their contents, representing a dynamic, bioavailable pool of BDNF. Hypoxia also independently activates platelets; therefore the combination of these stressors provides a unique model to examine the role of platelets in liberating BDNF and to quantify its flux across the brain during exercise. Twelve healthy adults (six women; 28 ± 4 years) performed exercise to exhaustion at sea level (340 m) and after 6–8 days at high altitude (3800 m) in a repeated-measures cross-over design. Simultaneous radial arterial and internal jugular venous blood samples were collected within the last 2 min of maximal exercise to quantify BDNF across the brain, alongside platelet concentration and platelet factor 4 (PF4), another neurogenic factor and a biomarker of platelet activation. At sea level, maximal exercise doubled free BDNF (P < 0.001) with no difference between arterial and venous circulations (P = 0.849). At high altitude, there was a pronounced veno-arterial difference indicating net release of BDNF (P = 0.003), and in addition, exercise caused a similar doubling in free BDNF (P < 0.001). Platelet concentration decreased by a third across the brain with exercise at high altitude (P = 0.002), but not sea level, and PF4 release was strongly correlated with BDNF release (r = 0.61, P < 0.001). Platelet activation across the human brain during exercise and hypoxia liberates BDNF and PF4 and may contribute to the neurotrophic effect of exercise.