Altered expression of KCC2 in GABAergic interneuron contributes prenatal stress-induced epileptic spasms in infant rat

被引:13
作者
Baek, Hyunjung [1 ,2 ]
Yi, Min-Hee [1 ]
Pandit, Sudip [3 ]
Park, Jin Bong [3 ]
Kwon, Hyeok Hee [1 ,2 ]
Zhang, Enji [1 ]
Kim, Sena [1 ,4 ]
Shin, Nara [1 ,5 ]
Kim, Eunjee [1 ]
Lee, Young Ho [1 ]
Kim, Yonghyun [6 ]
Kim, Dong Woon [1 ]
Kang, Joon Won [2 ]
机构
[1] Chungnam Natl Univ, Sch Med, Dept Anat, Brain Res Inst, Munwha Ro 266, Daejeon 301747, South Korea
[2] Chungnam Natl Univ, Sch Med, Chungnam Natl Univ Hosp, Dept Pediat,Brain Res Inst, Munwha Ro 282, Daejeon 301721, South Korea
[3] Chungnam Natl Univ, Dept Physiol, Brain Res Inst, Sch Med, Munwha Ro 266, Daejeon 301747, South Korea
[4] Chungnam Natl Univ Hosp, Dept Plast Surg, Munwha Ro 282, Daejeon 301721, South Korea
[5] Chungnam Natl Univ Hosp, Anesthesia & Pain Med, Munwha Ro 282, Daejeon 301721, South Korea
[6] Univ Alabama, Dept Chem & Biol Engn, Tuscaloosa, AL 35487 USA
关键词
Epilepsy; Prenatal stress; Seizure; Gamma-aminobutyric acid; Glutamate decarboxylase 67; K+/Cl- co-transporter; ANTENATAL CORTICOSTEROIDS; SEIZURE SUSCEPTIBILITY; DEVELOPING HIPPOCAMPUS; IMMOBILIZATION STRESS; EXCITATORY ACTIONS; PREPUBERTAL RATS; BEHAVIOR; MODEL; GABA; EXPOSURE;
D O I
10.1016/j.neuint.2016.05.006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:57 / 64
页数:8
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