Khazipov Rustem, Tyzio Roman, Ben-Ari Yehezkel
INMED-INSERM U29, Université de la Méditerranée, Marseille, France.
Prog Brain Res. 2008;170:243-57. doi: 10.1016/S0079-6123(08)00421-4.
Oxytocin (OXT) exerts multiple effects in the adult central nervous system. However, little is known about the effects of OXT on foetal neurons during delivery, at the time when a surge of OXT occurs. In a recent study, the effects of OXT on gamma-aminobutyric acid (GABA) signalling have been reported in foetal and newborn rats. In the immature rat hippocampal and neocortical neurons at birth, endogenous OXT induced a switch in the action of GABA from excitatory to inhibitory. This excitatory-to-inhibitory switch was caused by a switch in the polarity of the GABAergic responses from depolarizing to hyperpolarizing, reflecting a decrease in the intracellular chloride concentration. The effects of OXT were mimicked and occluded by bumetanide, a selective blocker of the chloride co-transporter NKCC1, suggesting that the effects of OXT involve inhibition of NKCC1. Neuronal death caused by anoxic-aglycaemic episodes was substantially delayed in the foetal hippocampus by endogenous OXT. These findings suggest that OXT plays important role in the preparation of the foetal brain to delivery.
催产素(OXT)在成体中枢神经系统中发挥多种作用。然而,在分娩期间OXT激增时,关于OXT对胎儿神经元的影响却知之甚少。在最近一项研究中,已报道了OXT对胎儿和新生大鼠γ-氨基丁酸(GABA)信号传导的影响。在出生时未成熟的大鼠海马和新皮质神经元中,内源性OXT诱导GABA的作用从兴奋性转变为抑制性。这种兴奋性到抑制性的转变是由GABA能反应的极性从去极化转变为超极化引起的,这反映了细胞内氯离子浓度的降低。布美他尼(一种氯离子共转运体NKCC1的选择性阻滞剂)模拟并阻断了OXT的作用,表明OXT的作用涉及对NKCC1的抑制。内源性OXT使胎儿海马中由缺氧-无糖发作引起的神经元死亡显著延迟。这些发现表明,OXT在胎儿大脑为分娩做准备过程中发挥重要作用。