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
Subchronic N-acetylcysteine Treatment Decreases Brain Kynurenic Acid Levels and Improves Cognitive Performance in Mice
Tonali Blanco Ayala,Daniela Ramírez Ortega,Paulina Ovalle Ovalle Rodríguez,Benjamín Pineda,Gonzalo Pérez de la Cruz,Dinora González González Esquivel,Robert Schwarcz,Korrapati V. Sathyasaikumar,Anabel Jiménez Anguiano,Verónica Pérez de la Cruz +9 more
TL;DR: In this article, repeated systemic NAC (100 mg/kg, i.p.) daily for 7 days was examined if repeated systemic administration of NAC influenced brain kynurenic acid and cognitive performance in mice.
Journal ArticleDOI
High-Fat Diet and Voluntary Chronic Aerobic Exercise Recover Altered Levels of Aging-Related Tryptophan Metabolites along the Kynurenine Pathway.
Keon-Joo Lee,Keon-Joo Lee,Keun Hwa Jung,Keun Hwa Jung,Joo Youn Cho,Soon-Tae Lee,Soon-Tae Lee,Hwa Suk Kim,Jun Hwa Shim,Sang Kun Lee,Sang Kun Lee,Manho Kim,Manho Kim,Kon Chu,Kon Chu +14 more
TL;DR: Tryptophan metabolites and their associated enzyme activities were significantly altered during aging, and the KYNA/3-HK ratio was a meaningful indicator of aging.
Dissertation
Neuropathology of Post-stroke Depression: Possible Role of Inflammatory Molecules and Indoleamine 2,3-dioxygenase
TL;DR: Higher mean KYN/TRP ratios were demonstrated in stroke patients with depressive symptoms, suggesting that both mechanisms may play an etiological role in PSD.
Journal ArticleDOI
A chicken and egg scenario in psychoneuroimmunology: Bidirectional mechanisms linking cytokines and depression
Manivel Rengasamy,Anna L. Marsland,Meredith Spada,Kimberly Hsiung,Tessa Kovats,Rebecca B. Price +5 more
TL;DR: Bidirectional evidence exists for several mechanisms in the relationship between cytokines and depression, and key areas for future research are identified, including the need for longitudinal clinical studies to examine causality in pertinent mechanisms and modulating factors in the cytokine-depression interaction.
Journal ArticleDOI
The role of anthranilic acid in the increase of depressive symptoms and major depressive disorder during treatment for hepatitis C with pegylated interferon-α2a and oral ribavirin.
Tomasz Pawłowski,Dariusz Pawlak,Małgorzata Inglot,Małgorzata Zalewska,Dominik Marciniak,Jolanta Bugajska,Justyna Janocha-Litwin,Krzysztof Małyszczak +7 more
TL;DR: In this paper, the authors evaluated the relationship between depressive symptoms and kynurenine, tryptophan, anthranilic acid, kynurenic acid concentrations, indolamine 2,3-dioxygenase (IDO) activity and Tryptophan availability to the brain.
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.
Journal ArticleDOI
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.