Suicidality and Activation of the Kynurenine Pathway of Tryptophan Metabolism

2016 ◽  
pp. 269-284 ◽  
Author(s):  
Elena Y. Bryleva ◽  
Lena Brundin
Keyword(s):  
Kynurenine Pathway ◽  
Tryptophan Metabolism

scholarly journals The Effects of Naphthenic Acids on Tryptophan Metabolism and Peripheral Serotonin Signalling

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A493-A493
Author(s):  
Laiba Jamshed ◽  
Genevieve A Perono ◽  
Shanza Jamshed ◽  
Kim Ann Cheung ◽  
Philippe J Thomas ◽  
...  
Keyword(s):  
Oil Sands ◽  
Naphthenic Acid ◽  
Kynurenine Pathway ◽  
Naphthenic Acids ◽  
Tryptophan Metabolism ◽  
Lipid Homeostasis ◽  
Prostaglandin E ◽  
Serotonin Synthesis ◽  
Active Metabolites ◽  
Glucose And Lipid Homeostasis

Abstract Introduction: Serotonin produced in the periphery has been shown to affect glucose and lipid homeostasis. The availability of the amino acid tryptophan, the precursor of serotonin, affects serotonin availability. In addition, the metabolism of tryptophan via the kynurenine pathway produces physiologically active metabolites which have been shown to be altered under conditions of increased adiposity and dysglycemia. There is now evidence demonstrating some environmental xenobiotics, known to affect glucose and lipid homeostasis, can also alter serotonin production and key components of the kynurenine pathway. Recent evidence suggests that exposure to compounds present in petroleum and wastewaters from oil and gas extraction sites can impact endocrine signaling and result in aberrant lipid accumulation and altered glycemic control. However, whether any of these changes can be causally ascribed to altered serotonin synthesis/signaling or tryptophan metabolism remains unknown. The goal of this study was to determine the effects of exposure to naphthenic acid (NA), a key toxicant found in wastewater from bitumen (thick crude oil present in oil sands deposits) extraction on the enzymes involved in tryptophan metabolism and serotonin production. Methods: McA-RH7777 rat hepatoma cells, were exposed to a technical NA mixture for 48 hours at concentrations within the reported range of NA found in wastewaters from oil extraction. We assessed mRNA expression for key rate-limiting enzymes involved in tryptophan metabolism that lead to either serotonin [Tph1] and/or kynurenine [Ido2 and Tdo2] production, as well as downstream enzymes in the kynurenine pathway [Afmid, Kyat1, Aadat, Kyat3, Kmo, Haao, Acmsd, Qprt]. We also examined the effects of NA on prostaglandin synthesis [Ptgs1, Ptgs2, Ptges] and signalling [Ptger2, Ptger4] as prostaglandins have been shown to be induced by serotonin and are linked to hepatic fat accumulation. Results: NA treatment significantly increased Tph1 and Ido2 expression; this occurred in association with a significant increase in the expression of the inducible prostaglandin synthase Ptgs2 (COX-2), prostaglandin E synthase Ptges, and prostaglandin receptors Ptger2 and Ptger4. Acmsd was the only downstream enzyme in the kynurenine pathway that was significantly altered by NA treatment. Conclusion: These results provide proof-of-concept that compounds associated with oil sands extraction have the potential to perturb key components of serotonin synthesis (Tph1) and tryptophan metabolism (Ido2, Acmsd). Furthermore, we found that the increase in Tph1 expression paralleled expression of Ptgs2. As increased prostaglandin production has been reported in association with nonalcoholic steatohepatitis, these data provide a potential mechanism by which exposure to NA and other petroleum-based compounds may increase the risk of metabolic disease.

scholarly journals Maternal Inflammation Results in Altered Tryptophan Metabolism in Rabbit Placenta and Fetal Brain

2017 ◽  
Vol 39 (5) ◽  
pp. 399-412 ◽  
Author(s):  
Monica Williams ◽  
Zhi Zhang ◽  
Elizabeth Nance ◽  
Julia L. Drewes ◽  
Wojciech G. Lesniak ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Microglial Activation ◽  
Rabbit Model ◽  
Fetal Brain ◽  
Kynurenine Pathway ◽  
Tryptophan Metabolism ◽  
Maternal Inflammation ◽  
Newborn Brain ◽  
Tryptophan Pathway ◽  
Tryptophan Metabolites

Maternal inflammation has been linked to neurodevelopmental and neuropsychiatric disorders such as cerebral palsy, schizophrenia, and autism. We had previously shown that intrauterine inflammation resulted in a decrease in serotonin, one of the tryptophan metabolites, and a decrease in serotonin fibers in the sensory cortex of newborns in a rabbit model of cerebral palsy. In this study, we hypothesized that maternal inflammation results in alterations in tryptophan pathway enzymes and metabolites in the placenta and fetal brain. We found that intrauterine endotoxin administration at gestational day 28 (G28) resulted in a significant upregulation of indoleamine 2,3-dioxygenase (IDO) in both the placenta and fetal brain at G29 (24 h after treatment). This endotoxin-mediated IDO induction was also associated with intense microglial activation, an increase in interferon gamma expression, and increases in kynurenine and the kynurenine pathway metabolites kynurenine acid and quinolinic acid, as well as a significant decrease in 5-hydroxyindole acetic acid (a precursor of serotonin) levels in the periventricular region of the fetal brain. These results indicate that maternal inflammation shunts tryptophan metabolism away from the serotonin to the kynurenine pathway, which may lead to excitotoxic injury along with impaired development of serotonin-mediated thalamocortical fibers in the newborn brain. These findings provide new targets for prevention and treatment of maternal inflammation-induced fetal and neonatal brain injury leading to neurodevelopmental disorders such as cerebral palsy and autism.

scholarly journals Tryptophan Metabolism Along the Kynurenine Pathway Downstream of Toll-like Receptor Stimulation in Peripheral Monocytes

2016 ◽  
Vol 84 (5) ◽  
pp. 262-271 ◽  
Author(s):  
F. Orhan ◽  
M. Bhat ◽  
K. Sandberg ◽  
S. Ståhl ◽  
F. Piehl ◽  
...  
Keyword(s):  
Kynurenine Pathway ◽  
Tryptophan Metabolism ◽  
Toll Like Receptor ◽  
Receptor Stimulation

The effect of age on the enzyme activities of tryptophan metabolism along the kynurenine pathway in rats

2005 ◽  
Vol 360 (1-2) ◽  
pp. 67-80 ◽  
Author(s):  
Stefano Comai ◽  
Carlo V.L. Costa ◽  
Eugenio Ragazzi ◽  
Antonella Bertazzo ◽  
Graziella Allegri
Keyword(s):  
Enzyme Activities ◽  
Kynurenine Pathway ◽  
Tryptophan Metabolism ◽  
Effect Of Age
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