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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Journal ArticleDOI
Brain Versus Blood: A Systematic Review on the Concordance Between Peripheral and Central Kynurenine Pathway Measures in Psychiatric Disorders
Katrien Skorobogatov,Livia De Picker,Robert Verkerk,Violette Coppens,Marion Leboyer,Norbert Müller,Manuel Morrens +6 more
TL;DR: In this paper, the concordance between peripheral and central (CSF or brain tissue) kynurenine metabolites was investigated, and the authors found that moderate to strong concordances were found between peripheral-and central concentrations not only in psychiatric disorders, but also in other (patho)physiological conditions.
Journal ArticleDOI
Increased levels of 3-hydroxykynurenine in different brain regions of rats with chronic renal insufficiency.
TL;DR: In this article, the levels of TRP, 3-hydroxykynurenine (3-HK) and 3-kynurene (KYN) were measured in the plasma and in different brain regions of uremic rats.
Journal Article
Impact of different antipsychotics on cytokines and tryptophan metabolites in stimulated cultures from patients with schizophrenia.
Daniela Krause,Elif Weidinger,Catherine Dippel,Michael C. Riedel,Markus J. Schwarz,Norbert Müller,Aye-Mu Myint +6 more
TL;DR: Only two atypical antipsychotics were identified to reverse the imbalanced cytokine levels in schizophrenia and the low concentrations of tryptophan and kynurenine in these patients could be a sign of a fast degradation of tryPTophan - yet tryptophilean metabolites could not be changed by any of the investigated antipsychotic.
Journal ArticleDOI
Salivary kynurenic acid response to psychological stress: inverse relationship to cortical glutamate in schizophrenia
Joshua Chiappelli,Laura M. Rowland,Francesca M. Notarangelo,S. Andrea Wijtenburg,Marian A. R. Thomas,Ana Pocivavsek,Aaron Jones,Krista Wisner,Peter Kochunov,Robert Schwarcz,L. Elliot Hong +10 more
TL;DR: Findings suggest a potentially meaningful link between central glutamate levels and kynurenine pathway response to stress in individuals with schizophrenia.
Journal ArticleDOI
Intake of Seven Essential Amino Acids Improves Cognitive Function and Psychological and Social Function in Middle-Aged and Older Adults: A Double-Blind, Randomized, Placebo-Controlled Trial
Hiroyuki Suzuki,Daichi Yamashiro,Susumu Ogawa,Momoko Kobayashi,Daisuke Cho,Ai Iizuka,Masako Tsukamoto-Yasui,Takada Michihiro,Muneki Isokawa,Kenji Nagao,Yoshinori Fujiwara +10 more
TL;DR: Findings suggested that ingestion of the seven essential amino acids led to improved attention and cognitive flexibility and psychosocial functioning, which is expected to prevent cognitive decline.
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
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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.