Maternal oxytocin triggers a transient inhibitory switch in GABA signaling in the fetal brain during delivery.
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.
Tyzio
Roman
R
Institut de Neurobiologie de la Méditerranée, INSERM U29, Université de la Méditerranée, Campus Scientifique de Luminy, Boite Postale 13, 13273 Marseille Cedex 09, France.
Cossart
Rosa
R
Khalilov
Ilgam
I
Minlebaev
Marat
M
Hübner
Christian A
CA
Represa
Alfonso
A
Ben-Ari
Yehezkel
Y
Khazipov
Rustem
R
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*
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