Neonatal maternal separation delays the GABA excitatory-to-inhibitory functional switch by inhibiting KCC2 expression
Neonatal maternal separation delays the GABA excitatory-to-inhibitory functional switch by inhibiting KCC2 expression
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DOI：
10.1016/j.bbrc.2017.09.143
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发表时间：
2017-11-25
影响因子：
3.1
通讯作者：
Sato, Tomoaki
中科院分区：
文献类型：
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作者：
Furukawa, Minami;Tsukahara, Takao;Sato, Tomoaki
γ-氨基丁酸（GABA; GABA开关）的兴奋性到抑制性功能开关通常发生在海马体中出生后的第一到第二周，对于适当的中枢神经系统功能的发育是必要的。GABA能抑制功能的缺陷可导致兴奋/抑制（E/I）神经元失衡，这在许多神经退行性疾病中发现。在本研究中，我们研究了新生儿应激是否会影响GABA功能转换的时间，并导致青春期的疾病。在出生后第1-21天（PND）通过母体分离（MS）在C57 BL/6 J雄性小鼠幼仔中诱导新生儿应激。进行K+-Cl-共转运蛋白（KCC 2）和Ca（2+）成像的组织学定量，以检查MS期间GABA转换的时间。为了评估新生MS对青少年海马功能的影响，我们在PND 35 - 38定量KCC 2表达并评估海马相关行为任务。我们发现，MS延迟了海马GABA开关的时间，抑制了膜KCC 2表达的增加，KCC 2表达抑制持续到青春期。行为测试显示，在母亲分离的小鼠中，认知受损，注意力下降，过度运动和攻击性character.Taken在一起，我们的研究结果表明，新生儿应激延迟了GABA开关的时间，这可能会改变E/I平衡，并在以后的生活中引起神经退行性疾病。(C)2017爱思唯尔公司All rights reserved.
The excitatory-to-inhibitory functional switch of gamma-aminobutyric acid (GABA; GABA switch), which normally occurs in the first to the second postnatal week in the hippocampus, is necessary for the development of appropriate central nervous system function. A deficit in GABAergic inhibitory function could cause excitatory/inhibitory (E/I) neuron imbalance that is found in many neurodegenerative disorders. In the present study, we examined whether neonatal stress can affect the timing of the GABA functional switch and cause disorders during adolescence. Neonatal stress was induced in C57BL/6J male mouse pups by maternal separation (MS) on postnatal days (PND) 1-21. Histological quantification of K+-CI- co-transporter (KCC2) and ca(2+) imaging were performed to examine the timing of the GABA switch during the MS period. To evaluate the influence of neonatal MS on adolescent hippocampal function, we quantified KCC2 expression and evaluated hippocampal-related behavioral tasks at PND35 -38. We showed that MS delayed the timing of the GABA switch in the hippocampus and inhibited the increase in membrane KCC2 expression, with KCC2 expression inhibition persisting until adolescence. Behavioral tests showed impaired cognition, declined attention, hyperlocomotion, and aggressive character in maternally separated mice.Taken together, our results show that neonatal stress delayed the timing of the GABA switch, which could change the E/I balance and cause neurodegenerative disorders in later life. (C) 2017 Elsevier Inc. All rights reserved.