Transcranial direct current stimulation and sport performance: Brain Derived Neurotrophic Factor and neurotrophins as potential biomarkers of abuse
Authors: Botre Francesco , Biasini Giorgia Morgan , de la Torre Xavier , Rutigliano Lavinia , Sian Veronica , Donati Francesco 
Published: April 2020

BackgroundTranscranial direct current stimulation (tDCS) is an emerging, non‐invasive brain stimulation technique that delivers an electrical stimulus to a specific brain region. It may be used to improve cognitive performance and resistance to fatigue. These effects are similar to those of some brain‐boosting drugs banned by the World Anti‐Doping Agency (WADA). It was recently reported that tDCS causes changes in the serum levels of some neurotransmitters and neurotrophins, such as brain‐derived neurotrophic factor (BDNF). We plan to evaluate whether the abuse of tDCS in sport can be detected by monitoring markers of effect, i.e. by targeting specific neurotrophins in serum. We are here reporting our preliminary data on the reference levels of the selected neurotrophins in elite athletes.MethodsSerum samples from elite athletes selected for doping control and resulted negative for all substances/methods were assayed by ELISA kit from for Aviscera Bioscience and R&D systems Luminex “multiassay”. Genotyping of the samples for the presence of significant BDNF and pro‐BDNF related polymorphisms were performed by using Taqman probes and real‐time PCR methods and instrumentation (Thermo Fisher Scientific). Database includes both male and female subjects, age range 17–45 years. Serum samples from non‐athletes healthy individuals were also analyzed to assess baseline levels of the analytes in a time‐range of 24 hours and 1 months. All samples were analyzed after anonymization, and all participants subscribed an informed consent form.ResultsSerum levels of BDNF resulted always higher than proBDNF. BDNF resulted in a symmetric distribution, unlike proBDNF data that were strongly asymmetric, with a great difference between mean and median values. A weak negative correlation was observed between proBDNF and BDNF. No significant differences were observed for proBDNF and BDNF related to gender, age and sport discipline. Differences were instead detected between subjects tested “in competition” (IN) vs. “out of competition” (OUT): IN samples showed significantly higher levels, supporting previous literature data reporting that serum BDNF may increase as a consequence of physical exercise. Moreover, BDNF values in elite athletes were generally higher than those in non‐athletes. Longitudinal analysis of both proBDNF and BDNF revealed that the intra‐individual variability is considerably narrower than the inter‐individual variability. A common SNP polymorphism (rs6265, A>G) seems to impact only on proBDNF: individuals carrying the GG genotype showed lower basal level or proBDNF than normal or heterozygous subjects. Serum levels of other neurotrophins (NGF, NT‐3, NT‐4) were very low, with no statistical correlation to the other analytes.ConclusionsData we collected in this pilot suggest the possible selection of BDNF, proBDNF and their ratio as putative biomarkers to detect the abuse of tDCS in sport doping. An approach based on the longitudinal monitoring of the values rather the development of populational normality ranges seems to be the most appropriate strategy of detection.Support or Funding InformationFederazione Medico Sportiva Italiana