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    Restraint Stress during Pregnancy Rapidly Raises Kynurenic Acid Levels in Mouse Placenta and Fetal Brain

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    Author
    Notarangelo, F.M.
    Schwarcz, R.
    Date
    2017
    Journal
    Developmental Neuroscience
    Publisher
    S. Karger AG
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://www.doi.org/10.1159/000455228
    Abstract
    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.
    Keyword
    3-Hydroxykynurenine
    Development
    Kynurenine pathway
    Quinolinic acid
    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/10713/9877
    ae974a485f413a2113503eed53cd6c53
    10.1159/000455228
    Scopus Count
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    UMB Open Access Articles 2017

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