Quinolinic acid/tryptophan ratios predict neurological disease in SIV-infected macaques and remain elevated in the brain under cART

Journal of Neurovirology
Julia L DrewesM Christine Zink

Abstract

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 ...Continue Reading

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Citations

Nov 27, 2016·Glia·Natalie C ChenJulio Martín-García
Apr 5, 2017·Acta Crystallographica. Section D, Structural Biology·Lakshmi Swarna Mukhi PiduguEric A Toth
Mar 10, 2019·Scientific Reports·Paul CastellanoEliseo A Eugenin
Aug 27, 2015·International Journal of Tryptophan Research : IJTR·Vikram Mehraj, Jean-Pierre Routy
Dec 7, 2019·EBioMedicine·Stephani VelasquezEliseo A Eugenin
Jul 16, 2021·Frontiers in Microbiology·Xiaolei WangHuanbin Xu
Aug 29, 2021·Pathogens·Sonia MorettiAlessandra Borsetti

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