title: Maternal oxytocin triggers a transient inhibitory switch in GABA signaling in the fetal brain during delivery.
abstract: We report a signaling mechanism in rats between mother and fetus aimed at preparing fetal neurons for delivery. In immature neurons, gamma-aminobutyric acid (GABA) is the primary excitatory neurotransmitter. We found that, shortly before delivery, there is a transient reduction in the intracellular chloride concentration and an excitatory-to-inhibitory switch of GABA actions. These events were triggered by oxytocin, an essential maternal hormone for labor. In vivo administration of an oxytocin receptor antagonist before delivery prevented the switch of GABA actions in fetal neurons and aggravated the severity of anoxic episodes. Thus, maternal oxytocin inhibits fetal neurons and increases their resistance to insults during delivery.
authors.affiliation: Institut de Neurobiologie de la Méditerranée, INSERM U29, Université de la Méditerranée, Campus Scientifique de Luminy, Boite Postale 13, 13273 Marseille Cedex 09, France.
authors.forename: Roman
authors.initials: R
authors.lastname: Tyzio
authors.forename: Rosa
authors.initials: R
authors.lastname: Cossart
authors.forename: Ilgam
authors.initials: I
authors.lastname: Khalilov
authors.forename: Marat
authors.initials: M
authors.lastname: Minlebaev
authors.forename: Christian A
authors.initials: CA
authors.lastname: Hübner
authors.forename: Alfonso
authors.initials: A
authors.lastname: Represa
authors.forename: Yehezkel
authors.initials: Y
authors.lastname: Ben-Ari
authors.forename: Rustem
authors.initials: R
authors.lastname: Khazipov
mesh_terms: D000200:Action Potentials; D000818:Animals; D000831:Animals, Newborn; D001549:Benzamides / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D005260:Female; D005311:Fetal Hypoxia / Q000503:physiopathology; D005333:Fetus / Q000502:physiology*; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008431:Maternal-Fetal Exchange; D009433:Neural Inhibition; D009474:Neurons / Q000502:physiology*; D010121:Oxytocin / Q000494:pharmacology / Q000502:physiology*; D036801:Parturition; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D064506:Solute Carrier Family 12, Member 2; D014668:Vasotocin / Q000031:analogs & derivatives / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: C484315:(4-chloro-3-((3R)-(+)-5-chloro-1-(2,4-dimethoxybenzyl)-3-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl))-N-ethyl-N-(3-pyridylmethyl)-benzamide, hydrochloride; D001549:Benzamides; D002712:Chlorides; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D007211:Indoles; D011963:Receptors, GABA-A; D018045:Receptors, Oxytocin; C578879:Slc12a2 protein, rat; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; C047046:atosiban; D010121:Oxytocin; D005680:gamma-Aminobutyric Acid; D014668:Vasotocin