PMID- 25776527
OWN - NLM
STAT- MEDLINE
DCOM- 20160504
LR  - 20181113
IS  - 1538-2443 (Electronic)
IS  - 1355-0284 (Print)
IS  - 1355-0284 (Linking)
VI  - 21
IP  - 4
DP  - 2015 Aug
TI  - Quinolinic acid/tryptophan ratios predict neurological disease in SIV-infected 
      macaques and remain elevated in the brain under cART.
PG  - 449-63
LID - 10.1007/s13365-015-0334-2 [doi]
AB  - Activation of the kynurenine pathway (KP) of tryptophan catabolism likely 
      contributes to HIV-associated neurological disorders. However, KP activation in 
      brain tissue during HIV infection has been understudied, and the effect of 
      combination antiretroviral therapy (cART) on KP induction in the brain is 
      unknown. To examine these questions, tryptophan, kynurenine, 3-hydroxykynurenine, 
      quinolinic acid, and serotonin levels were measured longitudinally during SIV 
      infection in the striatum and CSF from untreated and cART-treated pigtailed 
      macaques. Messenger RNA (mRNA) levels of KP enzymes also were measured in the 
      striatum. In untreated macaques, elevations in KP metabolites coincided with 
      transcriptional induction of upstream enzymes in the KP. Striatal KP induction 
      was also temporally associated-but did not directly correlate-with serotonin 
      losses in the brain. CSF quinolinic acid/tryptophan ratios were found to be the 
      earliest predictor of neurological disease in untreated SIV-infected macaques, 
      outperforming other KP metabolites as well as the putative biomarkers 
      interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1). Finally, 
      cART did not restore KP metabolites to control levels in the striatum despite the 
      control of the virus, though CSF metabolite levels were normalized in most 
      animals. Overall, these results demonstrate that cerebral KP activation is only 
      partially resolved with cART and that CSF QUIN/TRP ratios are an early, 
      predictive biomarker of CNS disease.
FAU - Drewes, Julia L
AU  - Drewes JL
AD  - Department of Molecular and Comparative Pathobiology, Johns Hopkins University 
      School of Medicine, Baltimore, MD, 21205, USA.
FAU - Meulendyke, Kelly A
AU  - Meulendyke KA
FAU - Liao, Zhaohao
AU  - Liao Z
FAU - Witwer, Kenneth W
AU  - Witwer KW
FAU - Gama, Lucio
AU  - Gama L
FAU - Ubaida-Mohien, Ceereena
AU  - Ubaida-Mohien C
FAU - Li, Ming
AU  - Li M
FAU - Notarangelo, Francesca M
AU  - Notarangelo FM
FAU - Tarwater, Patrick M
AU  - Tarwater PM
FAU - Schwarcz, Robert
AU  - Schwarcz R
FAU - Graham, David R
AU  - Graham DR
FAU - Zink, M Christine
AU  - Zink MC
LA  - eng
GR  - P01 MH070306/MH/NIMH NIH HHS/United States
GR  - P40 OD013117/OD/NIH HHS/United States
GR  - R01 MH085554/MH/NIMH NIH HHS/United States
GR  - R01 MH087233/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150317
PL  - United States
TA  - J Neurovirol
JT  - Journal of neurovirology
JID - 9508123
RN  - 0 (Anti-Retroviral Agents)
RN  - 343-65-7 (Kynurenine)
RN  - 8DUH1N11BX (Tryptophan)
RN  - F6F0HK1URN (Quinolinic Acid)
SB  - IM
MH  - Animals
MH  - Anti-Retroviral Agents/pharmacology
MH  - Brain/*metabolism/virology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Gas Chromatography-Mass Spectrometry
MH  - Immunohistochemistry
MH  - Kynurenine/*metabolism
MH  - Macaca
MH  - Polymerase Chain Reaction
MH  - Quinolinic Acid/*metabolism
MH  - Simian Acquired Immunodeficiency Syndrome/*metabolism
MH  - Tryptophan/*metabolism
PMC - PMC4512924
MID - NIHMS672850
COIS- Conflict of Interest The authors declare that they have no conflicts of interest.
EDAT- 2015/03/18 06:00
MHDA- 2016/05/05 06:00
PMCR- 2016/08/01
CRDT- 2015/03/18 06:00
PHST- 2014/12/10 00:00 [received]
PHST- 2015/02/24 00:00 [accepted]
PHST- 2015/02/16 00:00 [revised]
PHST- 2015/03/18 06:00 [entrez]
PHST- 2015/03/18 06:00 [pubmed]
PHST- 2016/05/05 06:00 [medline]
PHST- 2016/08/01 00:00 [pmc-release]
AID - 10.1007/s13365-015-0334-2 [doi]
PST - ppublish
SO  - J Neurovirol. 2015 Aug;21(4):449-63. doi: 10.1007/s13365-015-0334-2. Epub 2015 
      Mar 17.