Positive association between serum quinolinic acid and functional connectivity following concussion.
Kynurenine pathway
Mild traumatic brain injury
Resting state
Journal
Brain, behavior, and immunity
ISSN: 1090-2139
Titre abrégé: Brain Behav Immun
Pays: Netherlands
ID NLM: 8800478
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
28
09
2020
revised:
29
10
2020
accepted:
05
11
2020
pubmed:
12
11
2020
medline:
28
5
2021
entrez:
11
11
2020
Statut:
ppublish
Résumé
The molecular mechanisms underlying the diverse psychiatric and neuropathological sequalae documented in subsets of athletes with concussion have not been identified. We have previously reported elevated quinolinic acid (QuinA), a neurotoxic kynurenine pathway metabolite, acutely following concussion in football players with prior concussion. Similarly, work from our group and others has shown that increased functional connectivity strength, assessed using resting state fMRI, occurs following concussion and is associated with worse concussion-related symptoms and outcome. Moreover, other work has shown that repetitive concussion may have cumulative effects on functional connectivity and is a risk factor for adverse outcomes. Understanding the molecular mechanisms underlying these cumulative effects may ultimately be important for therapeutic interventions or the development of prognostic biomarkers. Thus, in this work, we tested the hypothesis that the relationship between QuinA in serum and functional connectivity following concussion would depend on the presence of a prior concussion. Concussed football players with prior concussion (N = 21) and without prior concussion (N = 16) completed a MRI session and provided a blood sample at approximately 1 days, 8 days, 15 days, and 45 days post-injury. Matched, uninjured football players with (N = 18) and without prior concussion (N = 24) completed similar visits. The association between QuinA and global connectivity strength differed based on group (F(3, 127) = 3.46, p = 0.019); post-hoc analyses showed a positive association between QuinA and connectivity strength in concussed athletes with prior concussion (B = 16.05, SE = 5.06, p = 0.002, 95%CI[6.06, 26.03]), but no relationship in concussed athletes without prior concussion or controls. Region-specific analyses showed that this association was strongest in bilateral orbitofrontal cortices, insulae, and basal ganglia. Finally, exploratory analyses found elevated global connectivity strength in concussed athletes with prior concussion who reported depressive symptoms at the 1-day visit compared to those who did not report depressive symptoms (t(15) = 2.37, mean difference = 13.50, SE = 5.69, p = 0.032, 95%CI[1.36, 25.63], Cohen's d = 1.15.). The results highlight a potential role of kynurenine pathway (KP) metabolites in altered functional connectivity following concussion and raise the possibility that repeated concussion has a "priming" effect on KP metabolism.
Identifiants
pubmed: 33176183
pii: S0889-1591(20)32387-4
doi: 10.1016/j.bbi.2020.11.011
pmc: PMC7769223
mid: NIHMS1655271
pii:
doi:
Substances chimiques
Quinolinic Acid
F6F0HK1URN
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
531-540Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM121312
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS102225
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH113871
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS099789
Pays : United States
Informations de copyright
Copyright © 2020. Published by Elsevier Inc.
Références
Brain. 2013 Jan;136(Pt 1):43-64
pubmed: 23208308
Neurosci Biobehav Rev. 2015 Feb;49:8-18
pubmed: 25434880
Neuroimage. 2003 Oct;20(2):870-88
pubmed: 14568458
Neuropsychopharmacology. 2015 Jan;40(2):463-71
pubmed: 25074636
Neurosurgery. 2014 Sep;75 Suppl 1:S3-15
pubmed: 25006974
Neuropsychopharmacology. 2014 Jun;39(7):1777-85
pubmed: 24481242
PLoS One. 2017 Aug 1;12(8):e0178798
pubmed: 28763447
Nat Immunol. 2019 Jan;20(1):50-63
pubmed: 30478397
Mol Psychiatry. 2010 Apr;15(4):393-403
pubmed: 19918244
Mol Psychiatry. 2020 Jan;25(1):131-147
pubmed: 30980044
J Neurotrauma. 2020 Aug 15;37(16):1761-1776
pubmed: 32228145
Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10771-6
pubmed: 12134057
Neuropsychopharmacology. 2020 May;45(6):998-1007
pubmed: 31940661
Neurosci Lett. 1984 Aug 10;48(3):273-8
pubmed: 6237279
Eur J Neurol. 2006 Jan;13(1):30-42
pubmed: 16420391
Brain Behav Immun. 2015 May;46:55-9
pubmed: 25686798
Curr Top Behav Neurosci. 2017;31:249-267
pubmed: 27221627
Am J Sports Med. 2018 Jul;46(9):2263-2269
pubmed: 29879362
Nat Med. 2018 Sep;24(9):1351-1359
pubmed: 30127395
J Neuroimmunol. 1992 Sep;40(1):71-80
pubmed: 1387655
Lancet Infect Dis. 2010 May;10(5):338-49
pubmed: 20417416
Mov Disord. 2020 Nov;35(11):2028-2037
pubmed: 32710594
J Neurochem. 1989 Apr;52(4):1319-28
pubmed: 2538568
J Neurotrauma. 2019 Jun;36(11):1776-1785
pubmed: 30618331
Neuropsychology. 2015 Jan;29(1):59-75
pubmed: 24933491
Psychoneuroendocrinology. 2015 Dec;62:54-8
pubmed: 26232650
Br J Sports Med. 2017 Jun;51(12):919-929
pubmed: 28455364
Brain Behav Immun. 2018 Jan;67:59-64
pubmed: 28867283
Clin Neuropsychol. 2019 Aug;33(6):1016-1043
pubmed: 30618335
PLoS Pathog. 2016 Feb 18;12(2):e1005374
pubmed: 26891052
J Neuroinflammation. 2015 May 30;12:110
pubmed: 26025142
J Neurotrauma. 2017 Feb 15;34(4):824-837
pubmed: 27618518
J Neurochem. 2019 Dec;151(5):656-668
pubmed: 31376341
J Nucl Med. 2012 Apr;53(4):601-7
pubmed: 22414635
J Cereb Blood Flow Metab. 1998 Jun;18(6):610-5
pubmed: 9626184
Trends Neurosci. 2015 Oct;38(10):609-620
pubmed: 26442695
Neuroreport. 1997 Jan 20;8(2):431-4
pubmed: 9080423
Brain Connect. 2013;3(5):523-35
pubmed: 23980912
Biol Psychiatry. 2010 Oct 15;68(8):748-54
pubmed: 20719303
Neuroimage. 2015 Nov 15;122:1-5
pubmed: 26241684
Brain Inj. 2017;31(1):39-48
pubmed: 27901587
Nat Rev Neurol. 2014 Apr;10(4):217-24
pubmed: 24638131
Nat Rev Immunol. 2016 Oct;16(10):626-38
pubmed: 27546235
Sci Rep. 2017 Aug 24;7(1):8297
pubmed: 28839132
Br J Sports Med. 2017 Jun;51(12):969-977
pubmed: 28455362
Comput Biomed Res. 1996 Jun;29(3):162-73
pubmed: 8812068
Biol Psychiatry. 2005 Aug 1;58(3):190-6
pubmed: 16084839
Brain Behav Immun. 2016 Mar;53:39-48
pubmed: 26546831
J Neurotrauma. 2017 Dec 1;34(23):3262-3269
pubmed: 28882089
Brain Struct Funct. 2016 May;221(4):1911-25
pubmed: 25721800
PLoS One. 2015 Jun 26;10(6):e0131389
pubmed: 26114426
Neuroimage. 2010 Sep;52(3):1059-69
pubmed: 19819337
Brain Behav Immun. 2020 Jul;87:715-724
pubmed: 32147388
J Neurotrauma. 2020 Jan 1;37(1):152-162
pubmed: 31407610
J Mol Med (Berl). 2013 Jun;91(6):705-13
pubmed: 23636512
J Athl Train. 2003 Sep;38(3):238-244
pubmed: 14608434
Hum Brain Mapp. 2012 Aug;33(8):1914-28
pubmed: 21769991
Neuroimage. 2002 Oct;17(2):825-41
pubmed: 12377157
JAMA. 2016 Mar 8;315(10):1014-25
pubmed: 26954410
J Neurol Neurosurg Psychiatry. 2016 Jun;87(6):670-5
pubmed: 26269650
Glia. 2005 Jan 1;49(1):15-23
pubmed: 15390107
Biol Psychiatry. 2009 Sep 1;66(5):407-14
pubmed: 19423079
Med Sci Sports Exerc. 2007 Jun;39(6):903-9
pubmed: 17545878
Neuroimage. 2009 Oct 15;48(1):63-72
pubmed: 19573611
J Neurochem. 1997 Jan;68(1):280-8
pubmed: 8978736
Crit Care Med. 1999 Mar;27(3):493-7
pubmed: 10199527
J Leukoc Biol. 2008 Oct;84(4):932-9
pubmed: 18495785
Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10765-70
pubmed: 12134056
Hum Brain Mapp. 2019 Mar;40(4):1211-1220
pubmed: 30451340
J Neurotrauma. 2016 May 1;33(9):803-10
pubmed: 26413910
Neuropsychopharmacology. 2007 Nov;32(11):2384-92
pubmed: 17327884
J Neurotrauma. 2016 Jul 15;33(14):1349-57
pubmed: 26493952
Cancer Res. 2013 Jun 1;73(11):3225-34
pubmed: 23548271
Br J Sports Med. 2017 Jun;51(12):941-948
pubmed: 28566342
FEBS J. 2012 Apr;279(8):1356-65
pubmed: 22248144
J Neurotrauma. 2012 Nov 1;29(16):2521-38
pubmed: 22950876