Användning av xenotransfusion för att klargöra hur träning påverkar neurofunktion

Background.
Exercise training exerts positive effects on human performance by impacting many organs/systems in the body, including the musculoskeletal, cardiovascular, and nervous system. With respect to the brain, little is known regarding the mechanisms whereby exercise enhances neurofunction. One attractive hypothesis is that myokines/exerkines, signaling molecules released from muscle (or other tissues during exercise – exerkines), improve brain function. The study of human brain metabolic and structural changes after exercise training is limited by ethical considerations. Here, we propose a novel approach to study the effects of exercise training in humans on brain function. Xenotransfusion, the transfusion of mice with plasma from humans, followed by the sacrifice of mice and removal of tissues from the central nervous system, will allow for invasive study of neurofunction.

Purpose.
The purpose of this study is to determine the effects of plasma from untrained and trained humans on neurogenesis and neurotransmission of murine brain.

Methods.
Blood and muscle tissue will be obtained from 16 subjects (8 men and 8 women) before and after 12 weeks of exercise training. Plasma will be isolated and purified before injection into sedentary mice. Five weeks after transfusion, mice will be sacrificed and brain tissue and plasma will be harvested. Brain will be analyzed for neurogenesis, neuroprotection and neurotransmission (dopamine levels). Human and murine tissues will be analyzed for metabolites (metabolomics) and selected myokines.

Significance and originality.
The use of xenotransfusion to investigate the hypothesis that myokines are involved in enhanced brain function is novel. Positive results will facilitate identification of the circulating compound(s) involved in the beneficial effects of exercise. Our preliminary results indicate that training in mice enhances neuroprotection and neurotransmission in murine brain. If positive effects of trained plasma are obtained, this will support the involvement of myokines/exerkines in the effects of training on brain function. Understanding the mechanisms involved in enhanced brain function after training can be useful in enhancing performance under defined conditions (including activities that require concentration, or situations where central fatigue or injury occurs).

Träning medför positiva effekter på fysisk prestation genom att påverka många vävnader i kroppen, särskilt nervsystemet. Humanstudier av hjärnans förändringar efter träning begränsas dock av etiska överväganden. Här föreslår vi en ny metod för att studera effekterna av träning hos människor på hjärnans funktion. Xenotransfusion, transfusion av blodplasma från människor till möss, skulle möjliggöra invasiva studier av neuronalfunktion.

Syftet med denna studie är att undersöka effekterna av plasma från människor innan och efter en träningsperiod vad gäller hjärnfunktion hos möss. Plasma kommer att erhållas från försökspersoner före och efter träning och som sedan injiceras i otränade möss. Fem veckor senare kommer hjärnvävnaden analyseras för neuronalfunktion och associerade mekanismer.