Altered expression of KCC2 in GABAergic interneuron contributes prenatal stress-induced epileptic spasms in infant rat
Altered expression of KCC2 in GABAergic interneuron contributes prenatal stress-induced epileptic spasms in infant rat
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DOI：
10.1016/j.neuint.2016.05.006
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发表时间：
2016-07-01
影响因子：
4.2
通讯作者：
Kang, Joon Won
中科院分区：
文献类型：
--
作者：
Baek, Hyunjung;Yi, Min-Hee;Kang, Joon Won
怀孕期间的长期压力会导致后代的神经功能缺陷，大脑中的γ-氨基丁酸（GABA）系统发生改变。然而，目前尚不清楚产前应激如何影响成熟的GABA能中间神经元和婴儿癫痫发作的异常。在这里，我们表明，产前应激改变成熟的GABA抑制系统使用产前应激诱导的癫痫发作模型。在妊娠第15天的产前压力与betterdose或急性制动压力（AIS）增加了癫痫发作的敏感性，N-甲基-D-天冬氨酸触发的痉挛在出生后第15天。GABA在产前应激组的表达较低，这与谷氨酸脱羧酶67免疫阳性细胞的减少有关。产前应激显著降低了皮质K+/Cl-协同转运体（KCC 2）的表达。GABA诱导的膜去极化表明产前应激模型与对照相比具有显著更高的膜去极化。GABA增加KCC 2表达在培养的皮质含有切片。综上所述，我们的结果表明，产前应激与betteramine或AIS改变了GABA能祖细胞的成熟，并导致缺乏GABA输入，这反过来又降低了KCC 2的表达，降低癫痫发作阈值。我们的结论是，延迟GABA兴奋/抑制转换将使皮质神经元回路更容易受到产前应激诱发癫痫发作的兴奋性输入。(C)2016爱思唯尔有限公司版权所有。
Long-term stress during pregnancy causes neurologic deficits to offspring with altered gamma-aminobutyric acid (GABA) system in the brain. However, it is not clear how prenatal stress affects the maturing GABAergic interneurons and the resulting abnormalities in infantile seizures. Here, we showed that prenatal stress alters the maturation of GABA inhibitory system using a seizure model induced by prenatal stress. Prenatal stress with betamethasone or acute immobilization stress (AIS) on gestational day 15 increased the seizure susceptibility to N-methyl-D-aspartate-triggered spasms on postnatal day 15. The expression of GABA was lower in the prenatally stressed group, which compromise the decrease of glutamate decarboxylase 67-immunopositive cells. Prenatal stress markedly decreased the expression of K+/Cl- co-transporter (KCC2) in the cortex. GABA induced membrane depolarization demonstrated prenatal stress models had significant higher membrane depolarization compared to control. GABA increased KCC2 expression in cultured cortex-containing slices. Taken together, our results showed that prenatal stress with betamethasone or AIS altered the maturation of GABAergic progenitors and resulted in the lack of GABA input, which in turn, decreased KCC2 expression and lowered seizure threshold. We conclude that delayed GABA excitatory/inhibitory shift would render the cortical neuronal circuit more susceptible to excitatory input in prenatal stress induced seizure. (C) 2016 Elsevier Ltd. All rights reserved.