Long-lasting distortion of GABA signaling in MS/DB neurons after binge-like ethanol exposure during initial synaptogenesis.
Long-lasting distortion of GABA signaling in MS/DB neurons after binge-like ethanol exposure during initial synaptogenesis.
复制标题
在最初的突触发生过程中，暴饮暴食后，MS/DB 神经元中的 GABA 信号传导会出现长期扭曲。
DOI：
10.1016/j.brainres.2013.04.054
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发表时间：
2013
期刊：
影响因子：
2.9
通讯作者：
Frye,GeraldD
中科院分区：
文献类型：
--
作者：
Wang,Haiying;DuBois,DustinW;Tobery,AngelikaN;Griffith,WilliamH;Brandt,Paul;Frye,GeraldD
使用一个成熟的模型，狂欢样乙醇处理的大鼠出生后（PD）4-9天的幼崽，我们发现，成熟的GABA受体（GABAAR）的微型突触后电流（mPSC）的内侧隔/斜角带（MS/DB）神经元在PD 11-16脑切片基本上钝化。乙醇降低了mPSC的振幅，频率和衰减动力学，同时分别减弱或夸大唑吡坦和别孕烯醇酮的变构作用。乙醇在体内的影响是持久的，因为MS/DB GABAAR mPSC中的大多数变化直到PD 60-85仍然被观察到。在幼稚脑切片PD 4-16中成熟的MS/DB神经元显示出增加的mPSC频率、衰减动力学和唑吡坦敏感性，这与我们在培养的隔神经元中的早期发现几乎相同（DuBois et al.，2004年、2006年）。这些快速发展的mPSC参数在出生后的第一个月内继续成熟，然后在剩余的寿命中保持稳定。最后，在雄性和雌性动物的MS/DB神经元中存在GABAAR mPSC信号传导的等效乙醇诱导的改变。先前，我们显示培养的胚胎第20天间隔神经元的乙醇处理扭曲了GABAAR mPSC的成熟，预测MS/DB神经元中GABA能传递的早期阶段易受中毒损伤（DuBois等人，2004年、2006年）。由于体内模型中GABA能mPSC发育和乙醇诱导的变化的总体特征、时间和幅度如此紧密地反映了培养的隔神经元中的时间等效适应，这表明，体内和体外乙醇损伤GABA能突触发育的这种平行模型对于探索潜在治疗干预的功效和作用机制的转化研究应该是有用的。从细胞到整个动物。
Using a well-established model of binge-like ethanol treatment of rat pups on postnatal days (PD) 4–9, we found that maturation of GABAAreceptor (GABAAR) miniature postsynaptic currents (mPSCs) was substantially blunted for medial septum/diagonal band (MS/DB) neurons in brain slices on PD 11–16. Ethanol reduced mPSC amplitude, frequency, and decay kinetics, while attenuating or exaggerating allosteric actions of zolpidem and allopregnanolone, respectively. The impact of ethanol in vivo was long lasting as most changes in MS/DB GABAAR mPSCs were still observed as late as PD 60–85. Maturing MS/DB neurons in naïve brain slices PD 4–16 showed increasing mPSC frequency, decay kinetics, and zolpidem sensitivity that were nearly identical to our earlier findings in cultured septal neurons (DuBois et al., 2004, 2006). These rapidly developing mPSC parameters continued to mature through the first month of life then stabilized throughout the remainder of the lifespan. Finally, equivalent ethanol-induced alterations in GABAAR mPSC signaling were present in MS/DB neurons from both male and female animals. Previously, we showed ethanol treatment of cultured embryonic day 20 septal neurons distorts the maturation of GABAAR mPSCs predicting that early stages of GABAergic transmission in MS/DB neurons are vulnerable to intoxication injury (DuBois et al., 2004, 2006). Since the overall character, timing, and magnitude of GABAergic mPSC developmental- and ethanol-induced changes in the in vivo model so closely mirror chronologically equivalent adaptations in cultured septal neurons, this suggests that such parallel models of ethanol impairment of GABAergic synaptic development in vivo and in vitro should be useful for translational studies exploring the efficacy and mechanism of action of potential therapeutic interventions from the cellular to whole animal level.