OBJECTIVE: The purpose of this study was to determine whether placental-derived kynurenines (neuroactive metabolites that are derived from tryptophan) contributes to infection-mediated fetal cerebral injury. STUDY DESIGN: Placentae and cord blood were obtained from term deliveries (n = 16) and preterm deliveries with or without intrauterine bacterial infection (n = 8 per group). We investigated whether the placenta expressed messenger RNAs of kynurenine metabolite-forming enzymes, the effects of infection in vivo on the expression of these enzymes by the placenta, the in vitro effects of bacterial endotoxin lipopolysaccharide on expression and kynurenine metabolite output by the placenta, and the kynurenine metabolite levels in umbilical cord blood. RESULTS: Placentae expressed messenger RNA of tryptophan-degrading enzymes and synthesized several compounds. The expression of several enzymes increased significantly in placentae that were exposed to infection and/or lipopolysaccharide. Lipopolysaccharide also induced significant increases in placental kynurenine and quinolinic acid output. Kynurenine and quinolinic acid in cord blood of fetuses who were exposed to infection were elevated significantly. CONCLUSION: Inflammatory mediated release of kynurenines from placentae exposes the fetus to significant amounts of potentially neurotoxic substances.
OBJECTIVE: The purpose of this study was to determine whether placental-derived kynurenines (neuroactive metabolites that are derived from tryptophan) contributes to infection-mediated fetal cerebral injury. STUDY DESIGN: Placentae and cord blood were obtained from term deliveries (n = 16) and preterm deliveries with or without intrauterine bacterial infection (n = 8 per group). We investigated whether the placenta expressed messenger RNAs of kynurenine metabolite-forming enzymes, the effects of infection in vivo on the expression of these enzymes by the placenta, the in vitro effects of bacterial endotoxin lipopolysaccharide on expression and kynurenine metabolite output by the placenta, and the kynurenine metabolite levels in umbilical cord blood. RESULTS: Placentae expressed messenger RNA of tryptophan-degrading enzymes and synthesized several compounds. The expression of several enzymes increased significantly in placentae that were exposed to infection and/or lipopolysaccharide. Lipopolysaccharide also induced significant increases in placental kynurenine and quinolinic acid output. Kynurenine and quinolinic acid in cord blood of fetuses who were exposed to infection were elevated significantly. CONCLUSION: Inflammatory mediated release of kynurenines from placentae exposes the fetus to significant amounts of potentially neurotoxic substances.
Authors: Monica Williams; Zhi Zhang; Elizabeth Nance; Julia L Drewes; Wojciech G Lesniak; Sarabdeep Singh; Diane C Chugani; Kannan Rangaramanujam; David R Graham; Sujatha Kannan Journal: Dev Neurosci Date: 2017-05-11 Impact factor: 2.984
Authors: Lisa C Hutton; Edwin Yan; Tamara Yawno; Margie Castillo-Melendez; Jon J Hirst; David W Walker Journal: Cerebellum Date: 2014-12 Impact factor: 3.847
Authors: Stacey J Ellery; Meredith Kelleher; Peta Grigsby; Irina Burd; Jan B Derks; Jon Hirst; Suzanne L Miller; Larry S Sherman; Mary Tolcos; David W Walker Journal: J Physiol Date: 2018-07-21 Impact factor: 5.182
Authors: Linda T Roten; Matthew P Johnson; Siri Forsmo; Elizabeth Fitzpatrick; Thomas D Dyer; Shaun P Brennecke; John Blangero; Eric K Moses; Rigmor Austgulen Journal: Eur J Hum Genet Date: 2008-09-10 Impact factor: 4.246