A preliminary model of football-related neural stress that integrates metabolomics with transcriptomics and virtual reality

• Published in: iScience Vol. 25; no. 1; p. 103483
• Main Authors: Vike, Nicole L., Bari, Sumra, Stetsiv, Khrystyna, Walter, Alexa, Newman, Sharlene, Kawata, Keisuke, Bazarian, Jeffrey J., Martinovich, Zoran, Nauman, Eric A., Talavage, Thomas M., Papa, Linda, Slobounov, Semyon M., Breiter, Hans C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.01.2022; Elsevier
• Subjects: Computer graphics; Metabolomics; Transcriptomics; Trauma; Metabolomics; Transcriptomics; Trauma; Computer graphics
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2021.103483

Research suggests contact sports affect neurological health. This study used permutation-based mediation statistics to integrate measures of metabolomics, neuroinflammatory miRNAs, and virtual reality (VR)-based motor control to investigate multi-scale relationships across a season of collegiate American football. Fourteen significant mediations (six pre-season, eight across-season) were observed where metabolites always mediated the statistical relationship between miRNAs and VR-based motor control (pSobelperm≤ 0.05; total effect > 50%), suggesting a hypothesis that metabolites sit in the statistical pathway between transcriptome and behavior. Three results further supported a model of chronic neuroinflammation, consistent with mitochondrial dysfunction: (1) Mediating metabolites were consistently medium-to-long chain fatty acids, (2) tricarboxylic acid cycle metabolites decreased across-season, and (3) accumulated head acceleration events statistically moderated pre-season metabolite levels to directionally model post-season metabolite levels. These preliminary findings implicate potential mitochondrial dysfunction and highlight probable peripheral blood biomarkers underlying repetitive head impacts in otherwise healthy collegiate football athletes. [Display omitted] •Permutation-based mediation statistics can be applied to multi-scale biology problems•Fatty acids were a critical link between elevated miRNAs and motor control•HAEs interacted with pre-season metabolite levels to model post-season levels•Together, our observations point to brain-related mitochondrial dysfunction Trauma; Metabolomics; Transcriptomics; Computer graphics