Journal ArticleDOI
Blood–Brain Barrier Transport of Kynurenines: Implications for Brain Synthesis and Metabolism
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TLDR
The results demonstrate the saturable transfer of L‐KYN across the blood–brain barrier and suggest that circulating L‐ KYN, 3‐HKYN, and ANA may each contribute significantly to respective cerebral pools under normal conditions.Abstract:
To evaluate the potential contribution of circulating kynurenines to brain kynurenine pools, the rates of cerebral uptake and mechanisms of blood-brain barrier transport were determined for several kynurenine metabolites of tryptophan, including L-kynurenine (L-KYN), 3-hydroxykynurenine (3-HKYN), 3-hydroxyanthranilic acid (3-HANA), anthranilic acid (ANA), kynurenic acid (KYNA), and quinolinic acid (QUIN), in pentobarbital-anesthetized rats using an in situ brain perfusion technique. L-KYN was found to be taken up into brain at a significant rate [permeability-surface area product (PA) = 2-3 x 10(-3) ml/s/g] by the large neutral amino acid carrier (L-system) of the blood-brain barrier. Best-fit estimates of the Vmax and Km of saturable L-KYN transfer equalled 4.5 x 10(-4) mumol/s/g and 0.16 mumol/ml, respectively. The same carrier may also mediate the brain uptake of 3-HKYN as D,L-3-HKYN competitively inhibited the brain transfer of the large neutral amino acid L-leucine. For the other metabolites, uptake appeared mediated by passive diffusion. This occurred at a significant rate for ANA (PA, 0.7-1.6 x 10(-3) ml/s/g), and at far lower rates (PA, 2-7 x 10(-5) ml/s/g) for 3-HANA, KYNA, and QUIN. Transfer for KYNA, 3-HANA, and ANA also appeared to be limited by plasma protein binding. The results demonstrate the saturable transfer of L-KYN across the blood-brain barrier and suggest that circulating L-KYN, 3-HKYN, and ANA may each contribute significantly to respective cerebral pools. In contrast, QUIN, KYNA, and 3-HANA cross the blood-brain barrier poorly, and therefore are not expected to contribute significantly to brain pools under normal conditions.read more
Citations
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Antibodies to quinolinic acid reveal localization in select immune cells rather than neurons or astroglia
TL;DR: Findings indicate an immune system origin for quinolinic acid, and implicate immune cells in excitotoxic CNS pathologies, and raise the possibility that quinlinic acid is a unique cytokine in immune system signal transmission.
Journal ArticleDOI
Association between single nucleotide polymorphisms of TPH1 and TPH2 genes, and depressive disorders.
Paulina Wigner,Piotr Czarny,Ewelina Synowiec,Michal Bijak,Katarzyna Bialek,Monika Talarowska,Piotr Gałecki,Janusz Szemraj,Tomasz Sliwinski +8 more
TL;DR: The hypothesis regarding the involvement of the pathway in the pathogenesis of depression is supported, as each of the studied polymorphisms modulated the risk of depression for selected genotypes and alleles.
Journal ArticleDOI
Kynurenine Pathway in Autism Spectrum Disorders in Children.
TL;DR: There is an increased neurotoxic potential and also a possible lower KYN aminotransferase activity in ASD, according to the serum levels of TRP, KYN, kynurenic acid, 3-hydroxykynurenine, and quinolinic acid.
Journal ArticleDOI
Tryptophan via serotonin/kynurenine pathways abnormalities in a large cohort of aggressive inmates: markers for aggression.
Stefano Comai,Antonella Bertazzo,Jeanne Vachon,Marc S. Daigle,Jean Toupin,Gilles Côté,Gustavo Turecki,Gabriella Gobbi +7 more
TL;DR: While circulating Trp is reduced in aggressive individuals, the combination of biological (5-HT/Trp ratio) and psychopathological (antisocial behavior and GAF) markers discriminates between aggressive and non-aggressive behavior suggesting the potential of a multi-marker approach in psychiatry given the heterogenic nature of mental diseases.
Journal ArticleDOI
Unexpected effects of peripherally administered kynurenic acid on cortical spreading depression and related blood-brain barrier permeability.
Gáspár Oláh,Judit Herédi,Ákos Menyhárt,Zsolt Czinege,Dávid Nagy,János Fuzik,Kitti Kocsis,Levente Knapp,Erika Krucsó,Levente Gellért,Zsolt Kis,Tamás Farkas,Ferenc Fülöp,Árpád Párdutz,János Tajti,László Vécsei,József Toldi +16 more
TL;DR: Investigation of the effects of two N-methyl-D-aspartate receptor antagonists, endogenous kynurenic acid (KYNA) and dizocilpine, on CSD and the related blood–brain barrier permeability in rats suggests that KYNA itself or its derivatives may offer a new approach in the therapy of migraines.
References
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Journal ArticleDOI
Quinolinic acid: an endogenous metabolite that produces axon-sparing lesions in rat brain
TL;DR: Intracerebral injection of the neuroexcitatory tryptophan metabolite, quinolinic acid, has behavioral, neurochemical and neuropathological consequences reminiscent of those of exogenous excitotoxins, such as kainic and ibotenic acids.
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Distinct mediating systems for the transport of neutral amino acids by the ehrlich cell
Journal ArticleDOI
Amino acid assignment to one of three blood-brain barrier amino acid carriers
William H. Oldendorf,John Szabo +1 more
TL;DR: Affinity for a basic amino acid carrier system was demonstrated for arginine, ornithine, and lysine and a third, low-capacity independent carrier system transporting aspartic and glutamic acids was demonstrated.
Journal ArticleDOI
An in situ brain perfusion technique to study cerebrovascular transport in the rat
TL;DR: The in situ brain perfusion technique is a sensitive new method to study cerebrovascular transfer in the rat and permits absolute control of perfusate composition.