Restraint Stress during Pregnancy Rapidly Raises Kynurenic Acid Levels in Mouse Placenta and Fetal Brain
Date
2017Journal
Developmental NeurosciencePublisher
S. Karger AGType
Article
Metadata
Show full item recordAbstract
Stressful events during pregnancy adversely affect brain development and may increase the risk of psychiatric disorders later in life. Early changes in the kynurenine (KYN) pathway (KP) of tryptophan (TRP) degradation, which contains several neuroactive metabolites, including kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), and quinolinic acid (QUIN), may constitute a molecular link between prenatal stress and delayed pathological consequences. To begin testing this hypothesis experimentally, we examined the effects of a 2-h restraint stress on KP metabolism in pregnant FVB/N mice on gestational day 17. TRP, KYN, KYNA, 3-HK, and QUIN levels were measured in maternal and fetal plasma and brain, as well as in the placenta, immediately after stress termination and 2 h later. In the same animals, we determined the activity of TRP 2,3-dioxygenase (TDO) in the maternal liver and in the placenta. Compared to unstressed controls, mostly transient changes in KP metabolism were observed in all of the tissues examined. Specifically, stress caused significant elevations of KYNA levels in the maternal plasma, placenta, and fetal brain, and also resulted in increased levels of TRP and KYN in the placenta, fetal plasma, and fetal brain. In contrast, 3-HK and QUIN levels remained unchanged from control values in all tissues at any time point. In the maternal liver, TDO activity was increased 2 h after stress cessation. Taken together, these findings indicate that an acute stress during the late gestational period preferentially affects the KYNA branch of KP metabolism in the fetal brain. Possible long-term consequences for postnatal brain development and pathology remain to be examined. Copyright 2017 S. Karger AG, Basel. Copyright: All rights reserved.Identifier to cite or link to this item
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85013676387&doi=10.1159%2f000455228&partnerID=40&md5=6c9e22fba4b1c224cfbdb247f726787e; http://hdl.handle.net/10713/9877ae974a485f413a2113503eed53cd6c53
10.1159/000455228
Scopus Count
Collections
Related articles
- Assessment of Prenatal Kynurenine Metabolism Using Tissue Slices: Focus on the Neosynthesis of Kynurenic Acid in Mice.
- Authors: Notarangelo FM, Beggiato S, Schwarcz R
- Issue date: 2019
- Prenatal Dynamics of Kynurenine Pathway Metabolism in Mice: Focus on Kynurenic Acid.
- Authors: Goeden N, Notarangelo FM, Pocivavsek A, Beggiato S, Bonnin A, Schwarcz R
- Issue date: 2017
- Activation of the kynurenine pathway and increased production of the excitotoxin quinolinic acid following traumatic brain injury in humans.
- Authors: Yan EB, Frugier T, Lim CK, Heng B, Sundaram G, Tan M, Rosenfeld JV, Walker DW, Guillemin GJ, Morganti-Kossmann MC
- Issue date: 2015 May 30
- Perinatal kynurenine 3-hydroxylase inhibition in rodents: pathophysiological implications.
- Authors: Ceresoli-Borroni G, Guidetti P, Amori L, Pellicciari R, Schwarcz R
- Issue date: 2007 Mar
- Evaluation of kynurenine pathway metabolism in Toxoplasma gondii-infected mice: implications for schizophrenia.
- Authors: Notarangelo FM, Wilson EH, Horning KJ, Thomas MA, Harris TH, Fang Q, Hunter CA, Schwarcz R
- Issue date: 2014 Jan