The Tryptophan Metabolite Indole-3-Propionic Acid Raises Kynurenic Acid Levels in the Rat Brain In Vivo.

Autor: Sathyasaikumar KV; Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, USA., Blanco-Ayala T; Neurobiochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery 'Manuel Velasco Suárez,' Mexico City, Mexico., Zheng Y; Departments of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden., Schwieler L; Departments of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden., Erhardt S; Departments of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden., Tufvesson-Alm M; Departments of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden., Poeggeler B; Department of Physiology, Johann-Friedrich-Blumenbach-Institute for Zoology and Anthropology, Georg-August-Universität Göttingen, Germany., Schwarcz R; Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, USA.
Jazyk: angličtina
Zdroj: International journal of tryptophan research : IJTR [Int J Tryptophan Res] 2024 Jun 20; Vol. 17, pp. 11786469241262876. Date of Electronic Publication: 2024 Jun 20 (Print Publication: 2024).
DOI: 10.1177/11786469241262876
Abstrakt: Alterations in the composition of the gut microbiota may be causally associated with several brain diseases. Indole-3-propionic acid (IPrA) is a tryptophan-derived metabolite, which is produced by intestinal commensal microbes, rapidly enters the circulation, and crosses the blood-brain barrier. IPrA has neuroprotective properties, which have been attributed to its antioxidant and bioenergetic effects. Here, we evaluate an alternative and/or complementary mechanism, linking IPrA to kynurenic acid (KYNA), another neuroprotective tryptophan metabolite. Adult Sprague-Dawley rats received an oral dose of IPrA (200 mg/kg), and both IPrA and KYNA were measured in plasma and frontal cortex 90 minutes, 6 or 24 hours later. IPrA and KYNA levels increased after 90 minutes and 6 hours (brain IPrA: ~56- and ~7-fold; brain KYNA: ~4- and ~3-fold, respectively). In vivo microdialysis, performed in the medial prefrontal cortex and in the striatum, revealed increased KYNA levels (~2.5-fold) following the administration of IPrA (200 mg/kg, p.o), but IPrA failed to affect extracellular KYNA when applied locally. Finally, treatment with 100 or 350 mg IPrA, provided daily to the animals in the chow for a week, resulted in several-fold increases of IPrA and KYNA levels in both plasma and brain. These results suggest that exogenously supplied IPrA may provide a novel strategy to affect the function of KYNA in the mammalian brain.
Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: R.S. is co-founder of Kynexis BV, which develops kynurenic acid-related compounds for human use.
(© The Author(s) 2024.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje