Exploratory study of sport-related concussion effects on peripheral micro-RNA expression

ABSTRACT

Objective: Explore changes in micro-RNA (miRNA) expression in blood after sport-related concussion (SRC) in collegiate athletes.

Methods: Twenty-seven collegiate athletes (~41% male, ~75% white, age 18.8 ± 0.8 years) provided both baseline and post-SRC blood samples. Serum was analyzed for expression of miR-153-3p (n = 27), miR-223-3p (n = 23), miR-26a-5p (n = 26), miR-423-3p (n = 23), and miR-let-7a-5p (n = 23) at both time points via quantitative polymerase chain reaction (qPCR). Nonparametric analyses were used to compare miRNA expression changes between baseline and SRC and to evaluate associations with clinical outcomes (symptom severity, cognition, balance, and oculomotor function, and clinical recovery time).

Results: Participants manifested a significant increase in miRNA expression following SRC for miR153-3p (Z = −2.180, p = .029, 59% of the participants increased post-SRC), miR223-3p (Z = −1.998, p = .046, 70% increased), and miR-let-7a-5p (Z = −2.190, p = .029, 65% increased). There were no statistically significant associations between changes in miRNA expression and clinical test scores, acute symptom severity, or clinical recovery time.

Conclusion: MiR-153-3p, miR-223-3p, and miR-let-7a-5p were significantly upregulated acutely following SRC in male and female collegiate athletes compared to baseline levels, though several athletes demonstrated no change or a decrease in expression. The biological mechanisms and functional implications of the increased expression of these circulating miRNA are unclear and require more research, as does their relevance to clinical outcomes.

KEYWORDS:

• Concussion
• biomarker
• micro-RNA
• miR-153
• miR-223
• miR-let-7a

Acknowledgments

We thank Dr. Laura Ranum, PhD (Director, Centre for NeuroGenetics, University of Florida College of Medicine) and Dr. Lien Nguyen, PhD (Postdoctoral Associate, Centre for NeuroGenetics, University of Florida College of Medicine) for providing an independent technical review of the methodology for this study. We also thank Dr. Shelley Heaton, PhD (Clinical Associate Professor, Department of Clinical and Health Psychology, University of Florida), for her determination that the manuscript is free of biased presentation based on her independent review, in accordance with requirements pertaining to the University of Florida’s financial stake in Banyan Biomarkers, Inc.

Disclosure statement

The authors have no relevant disclosure statements pertaining to the equipment, methods, or findings from the current study. BA received partial support from Banyan Biomarkers, Inc., for data collection and analysis. RB reports receiving funding from the National Center for Advancing Translational Sciences (UL1 RR029890) and National Institute of Aging (1Florida Alzheimer’s Disease Research Center; P50 AG047266). SD is supported by the 1Florida ADRC and AG047266. SD also reports serving on advisory boards for Amgen, Cognition Therapeutics, and Acumen, and chairs a Drug Monitoring Committee for Biogen. MJ is supported by McKnight Brain Institute and Florida Department of Elderly Affairs. RH holds stock in and is an employee of Banyan Biomarkers, Inc. JC is supported by Banyan Biomarkers Inc., Florida High Tech Corridor Matching Funds Program, and NCAA-DoD CARE Consortium (Award NO W81XWH-14-2- 0151). RB, AS, and GH report no relevant funding sources.