During the holiday season, Tyzio et al. give us one more reason to buy mom a really nice present. They report that maternal oxytocin, which induces uterine contractions during labor, protects the newborn brain from hypoxic/ischemic neuronal cell death in a recent article in Science.

GABA is the major inhibitory neurotransmitter in the adult brain, but it is the major excitatory neurotransmitter in the neonatal brain. The intracellular chloride concentration is elevated in neonatal relative to adult neurons at least in part because the transporter that shuttles chloride out of the cell is not yet expressed. Therefore the reversal potential, the membrane potential at which the concentration gradient driving an ion in one direction is balanced by the electrochemical gradient driving it in the other, is positive relative to the resting membrane potential, so the driving force for chloride is out of the cell, resulting in GABA-mediated depolarization. In the adult, the chloride exporter helps keep the intracellular chloride concentration low. The reversal potential for chloride is negative relative to the resting membrane potential, so the driving force for chloride is into the cell, resulting in GABA-mediated hyperpolarization.

In hippocampal slices from neonatal rats, the authors found that the number of neurons excited by GABA and the reversal potential for GABA neurons declined right around the time of birth, but rebounded shortly thereafter. During this period, the driving force for chloride ions changed from positive to negative, suggesting that GABA was inhibitory. Neurons grown in culture don’t experience this brief period of inhibition, so the authors proposed that a maternal factor might be the cause. Oxytocin reduced the number of hippocampal pyramidal cells excited by GABA and their intracellular chloride concentration relative to untreated cells. Pups from pregnant dams treated with an oxytocin receptor antagonist did not show GABA-mediated inhibition around the time of birth, suggesting that oxytocin is necessary for this short-lived effect.

So, why does GABA flip-flop? Birth can cause hypoxic conditions, which can lead to excitotoxic cell death. If the source for neuronal excitation is suddenly inhibitory, then the chances for cell death should decline. In the presence of an oxytocin receptor antagonist, hippocampal neurons from late embryonic rats were more vulnerable to anoxic depolarization relative to control neurons, suggesting that oxytocin is neuroprotective in the neonate.

What does this mean for babies born by Cesarean Section? I would think C-section avoids the anoxic conditions present in the birth canal. However, I wonder whether oxytocin analogs, like Pitocin and Syntocinon, that are used to induce labor affect fetal brain development or conversely offer extended protection for the neonatal brain.