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    Acute sleep deprivation during pregnancy in rats: Rapid elevation of placental and fetal inflammation and kynurenic acid

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    Author
    Baratta, A.M.
    Kanyuch, N.R.
    Pocivavsek, A.
    Date
    2020
    Journal
    Neurobiology of Stress
    Publisher
    Elsevier Inc
    Type
    Article
    
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    See at
    https://doi.org/10.1016/j.ynstr.2019.100204
    Abstract
    The kynurenine pathway (KP) is the dominant pathway for tryptophan degradation in the mammalian body and emerging evidence suggests that acute episodes of sleep deprivation (SD) disrupt tryptophan metabolism via the KP. Increases in the neuroactive KP metabolite kynurenic acid (KYNA) during pregnancy may lead to a higher risk for disrupted neurodevelopment in the offspring. As pregnancy is a critical period during which several factors, including sleep disruptions, could disrupt the fetal environment, we presently explored the relationship between maternal SD and KP metabolism and immune pathways in maternal, placenta, and fetal tissues. Pregnant Wistar rat dams were sleep deprived by gentle handling for 5 h from zeitgeber time (ZT) 0 to ZT 5. Experimental cohorts included: i) controls, ii) one session of SD on embryonic day (ED) 18 or iii) three sessions of SD occurring daily on ED 16, ED 17 and ED 18. Maternal (plasma, brain), placental and fetal (plasma, brain) tissues were collected immediately after the last session of SD or after 24 h of recovery from SD. Respective controls were euthanized at ZT 5 on ED 18 or ED 19. Maternal plasma corticosterone and fetal brain KYNA were significantly elevated only after one session of SD on ED 18. Importantly, maternal plasma corticosterone levels correlated significantly with fetal brain KYNA levels. In addition, placental levels of the proinflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6) were increased following maternal SD, suggesting a relationship between placental immune response to SD and fetal brain KYNA accumulation. Collectively, our results demonstrate that sleep loss during the last week of gestation can adversely impact maternal stress, placental immune function, and fetal brain KYNA levels. We introduce KYNA as a novel molecular target influenced by sleep loss during pregnancy. Copyright 2019 The Authors
    Sponsors
    The present study was supported in part by the National Institutes of Health [ R01 NS102209 ; 5T32GM092237-08 ] and a donation from the Clare E. Forbes Trust.
    Keyword
    Corticosterone
    Cytokines
    Kynurenic acid
    Pregnancy
    Sleep deprivation
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85078722548&doi=10.1016%2fj.ynstr.2019.100204&partnerID=40&md5=c6b4965cdf1bbb6dd96924cf9b602549; http://hdl.handle.net/10713/11991
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ynstr.2019.100204
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