Smaller Dentate Gyrus and CA2 and CA3 Volumes Are Associated with Kynurenine Metabolites in Collegiate Football Athletes.
An imbalance in kynurenine pathway metabolism is hypothesized to be associated with dysregulated glutamatergic neurotransmission, which has been proposed as a mechanism underlying the hippocampal volume loss observed in a variety of neurological disorders. Pre-clinical models suggest that the CA2-3 and dentate gyrus hippocampal subfields are particularly susceptible to excitotoxicity after experimental traumatic brain injury. We tested the hypothesis that smaller hippocampal volumes in collegiate football athletes with (n = 25) and without (n = 24) a concussion history would be most evident in the dentate gyrus and CA2-3 subfields relative to nonfootball healthy controls (n = 27). Further, we investigated whether the concentration of peripheral levels of kynurenine metabolites are altered in football athletes. Football athletes with and without a self-reported concussion history had smaller dentate gyrus (p < 0.05, p < 0.10) and CA2-3 volumes (p's < 0.05) relative to healthy controls. Football athletes with and without a concussion history had a trend toward lower (p < 0.10) and significantly lower (p < 0.05) kynurenine levels compared with healthy controls, while athletes with a concussion history had greater levels of quinolinic acid compared with athletes without a concussion history (p < 0.05). Finally, plasma levels of 3-hydroxykynurenine inversely correlated with bilateral hippocampal volumes in football athletes with a concussion history (p < 0.01), and left hippocampal volume was correlated with the ratio of kynurenic acid to quinolinic acid in football athletes without a concussion history (p < 0.05). Our results raise the possibility that abnormalities of the kynurenine metabolic pathway constitute a mechanism for hippocampal volume differences in the context of sports-related brain injury.
1 Department of Neurosurgery, Medical College of Wisconsin , Milwaukee, Wisconsin.|2 Laureate Institute for Brain Research , Tulsa, Oklahoma.
Timothy B
TB
Meier
2 Laureate Institute for Brain Research , Tulsa, Oklahoma.|3 Faculty of Community Medicine, The University of Tulsa , Tulsa, Oklahoma.
Jonathan
J
Savitz
2 Laureate Institute for Brain Research , Tulsa, Oklahoma.
Rashmi
R
Singh
4 Department of Surgery, University of Oklahoma College of Medicine , Tulsa, Oklahoma.|5 Department of Psychiatry, University of Oklahoma College of Medicine , Tulsa, Oklahoma.|6 Department of Pharmaceutical Sciences, University of Oklahoma College of Pharmacy , Tulsa, Oklahoma.|7 Department of Biochemistry and Microbiology, Oklahoma State University Center for Health Sciences , Tulsa, Oklahoma.
T Kent
TK
Teague
8 National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, Maryland.
Patrick S F
PS
Bellgowan
D000293:Adolescent; D000328:Adult; D056352:Athletes; D001265:Athletic Injuries / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology; D001924:Brain Concussion / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology; D056651:CA2 Region, Hippocampal / Q000000981:diagnostic imaging / Q000473:pathology*; D056654:CA3 Region, Hippocampal / Q000000981:diagnostic imaging / Q000473:pathology*; D018891:Dentate Gyrus / Q000000981:diagnostic imaging / Q000473:pathology*; D005538:Football; D006801:Humans; D007737:Kynurenine / Q000031:analogs & derivatives* / Q000097:blood*; D008279:Magnetic Resonance Imaging; D008297:Male; D017378:Quinolinic Acid / Q000097:blood*; D014495:Universities; D055815:Young Adult
C005045:3-hydroxykynurenine; D007737:Kynurenine; D017378:Quinolinic Acid
concussion; football; hippocampus; kynurenine pathway; mTBI