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Neurosteroid replacement therapy using tiagabine and zuranolone restores cerebellar neurodevelopment and reduces hyperactive behaviour following preterm birth.
J Dev Orig Health Dis
January 2025
School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, Australia.
Preterm birth exposes the neonate to hypoxic-ischaemic and excitotoxic insults that impair neurodevelopment and are magnified by the premature loss of placentally supplied, inhibitory neurosteroids. The cerebellum is a neuronally dense brain region, which undergoes critical periods of development during late gestation, when preterm births frequently occur. We propose that neurosteroid replacement therapy using tiagabine and zuranolone will protect the cerebellum against preterm-associated insults.
View Article and Find Full Text PDFPrenatal Stress Modulates Placental and Fetal Serotonin Levels and Determines Behavior Patterns in Offspring of Mice.
Int J Mol Sci
December 2024
Laboratory of Comparative Developmental Physiology, Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, 119334 Moscow, Russia.
Available evidence from animal studies suggests that placental serotonin plays an important role in proper fetal development and programming by altering brain circuit formation, which later translates into altered abnormal adult behaviors. Several environmental stimuli, including stress and maternal inflammation, affect placental and, hence, fetal serotonin levels and thus may disturb fetal brain development. We investigated the effect of prenatal stress of varying intensities on the formation of adaptive behaviors in mouse offspring and the role of placental serotonin in these processes.
View Article and Find Full Text PDFThe Placenta as the Main Source of Serotonin in Ontogenetic Dynamics: Inflammation-Induced Modulation of Placental Serotonin Can Be Prevented by Immunoglobulin Administration.
Int J Mol Sci
December 2024
Laboratory of Comparative Developmental Physiology, Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, Moscow 119334, Russia.
Placental serotonin is recognized as a key component of feto-placental physiology and can be influenced by environmental factors such as maternal diet, drugs, stress, and immune activation. In this study, we compared the contribution of placental and fetal sources to the maintenance of serotonin levels required for normal fetal development during ontogenetic dynamics. Our results demonstrated the leading role of the placenta at almost all stages of development.
View Article and Find Full Text PDFToll-like receptor 4 inhibition by pyridostigmine is associated with a reduction in hypertension and inflammation in rat models of preeclampsia.
J Hypertens
February 2025
Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, People's Republic of China.
Background: Preeclampsia (PE) is marked by hypertension and detrimental sterile inflammatory response. Despite the reported anti-inflammatory effect of pyridostigmine bromide (PYR) in different models, its anti-inflammatory mechanism in PE is unclear. This study assessed whether such an anti-inflammatory effect involves inhibition of placental Toll-like receptor 4 (TLR4) signaling.
View Article and Find Full Text PDFNicotine increases hepatocyte transthyretin turnover: A possible mechanism for the protective effect of smoking on preeclampsia?
Mol Cell Endocrinol
February 2025
Conjoint Endocrine Laboratory, Chemical Pathology, Pathology Queensland, Queensland Health, Herston, Qld 4029, Australia; School of Medicine, University of Queensland, Herston, Qld 4029, Australia; School of Biomedical Sciences, Queensland University of Technology, Brisbane, Qld 4000, Australia. Electronic address:
Transthyretin is a thyroid hormone binding protein with a major role in the distribution of thyroid hormones to peripheral tissues. In preeclampsia, the failing placenta releases soluble endoglin into the maternal circulation causing systemic vascular dysfunction. Our group has previously shown that transthyretin binds to soluble endoglin and is taken up as a complex into hepatocytes.
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