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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Action Potentials
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Animals
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Animals, Newborn
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Benzamides / pharmacology
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Chlorides / metabolism
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Female
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Fetal Hypoxia / physiopathology
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Fetus / physiology*
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GABA-A Receptor Agonists
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GABA-A Receptor Antagonists
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Hippocampus / cytology
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Hippocampus / embryology*
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Hippocampus / physiology
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In Vitro Techniques
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Indoles / pharmacology
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Maternal-Fetal Exchange
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Neural Inhibition*
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Neurons / physiology*
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Oxytocin / pharmacology
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Oxytocin / physiology*
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Parturition*
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Patch-Clamp Techniques
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Pregnancy
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Rats
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Rats, Wistar
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Receptors, GABA-A / physiology
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Receptors, Oxytocin / antagonists & inhibitors
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Signal Transduction
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Sodium Potassium Chloride Symporter Inhibitors
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Sodium-Potassium-Chloride Symporters / metabolism
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Solute Carrier Family 12, Member 2
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Vasotocin / analogs & derivatives
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Vasotocin / pharmacology
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gamma-Aminobutyric Acid / physiology*
Substances
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(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
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Benzamides
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Chlorides
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GABA-A Receptor Agonists
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GABA-A Receptor Antagonists
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Indoles
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Receptors, GABA-A
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Receptors, Oxytocin
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Slc12a2 protein, rat
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Sodium Potassium Chloride Symporter Inhibitors
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Sodium-Potassium-Chloride Symporters
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Solute Carrier Family 12, Member 2
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atosiban
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Oxytocin
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gamma-Aminobutyric Acid
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Vasotocin