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The kynurenine pathway activity in plasma and cerebrospinal fluid increases with ageing

(2018) Karsten, S. (Sjoukje)

Background: Ageing is a risk factor for many disorders. In elderly it leads to more production of cytokines like interferon- γ (INF-γ) and to a chronic low-grade inflammation. INF-γ can induce indoleamine 2,3-dioxygenase (IDO), which is an enzyme in the kynurenic pathway (KP). This pathway is responsible for the degradation of tryptophan (Trp) to the final product NAD+. The neurotoxic quinolinic acid (Quin) and neuroprotective kynurenic acid (Kyna) are important metabolites of the KP. More IDO induction leads to more tryptophan degradation along the KP and to more quinolinic acid synthesis. This could lead to more neurotoxicity. The aim of this study is to determine if and how the kynurenine pathway activity changes with ageing.
Method: The Anaesthetic Biobank of Cerebrospinal fluid included patients undergoing elective surgery with spinal anaesthesia. Trp, kynurenine (Kyn), Kyna and Quin levels were measured in the blood and cerebrospinal fluid (CSF) collected in the operating room. Pearson test, Spearman test and linear regression models were used for statistical analysis.
Results: n = 120. In plasma Trp (r = -0.358) had a significant negative correlation with age, whereas Kyn (r = 0.287) Kyn/Trp-ratio (r = 0.532) and Quin (r = 0.473) had a significant positive correlation with age. In CSF Kyn (r = 0.584), Kyn/Trp-ratio (r = 0,560),
Kyna (r = 0.609) and Quin (r = 0.680) had a positive correlation with age.
Conclusion: The kynurenine pathway activity increases with age. Our results are in line with results found in previous studies. The increased Kyn/Trp-ratios we found in both plasma and CSF imply an increased IDO-activity. The increased Quin level in plasma and CSF and the decreased plasma Kyna/Quin-ratio we found, suggests an imbalance in favour of neurotoxicity. However, more research regarding effects of plasma Quin and regarding direct links between low-grade inflammation, ageing and the kynurenine pathway activity is needed.






 
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