Modeling Fetal Alcohol Spectrum Disorder: Validating an Ex Vivo Primary Hippocampal Cell Culture System.
Modeling Fetal Alcohol Spectrum Disorder: Validating an Ex Vivo Primary Hippocampal Cell Culture System.
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胎儿酒精谱系障碍建模：验证离体原代海马细胞培养系统。
DOI：
10.1111/acer.13090
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Redei,EvaE
中科院分区：
文献类型：
--
作者：
Tunc-Ozcan,Elif;Ferreira,AdrianaB;Redei,EvaE
研究背景胎儿酒精谱系障碍（FASD）是导致智力低下的主要非遗传原因。迄今为止，还没有FASD的治疗方法。临床前体内和体外研究可以帮助确定其他疾病的新药物靶点。在这里，我们描述了一个离体模型，结合了产前乙醇（EtOH）暴露在体内的生理优势与原代胎儿海马培养的均匀性，以表征产前EtOH的影响。已知胰岛素信号通路参与海马功能。因此，我们比较了胎儿海马（体内）和原代海马培养（体外）之间的胰岛素信号通路基因的表达。产前EtOH的影响，在这2个范例的相似性将认为离体培养可接受的筛选可能的治疗FASD.MethodsPregnant Sprague-Dawley大鼠接受1的3饮食：自由标准实验室食物（对照-C），等热量的配对喂养（营养控制），和EtOH含有液体饮食从妊娠第8天（GD）。在GD 21（体内）或GD 18采集雄性和雌性胚胎campi进行原代培养（离体）。转录水平的Igf 2，Igf 2 r，Insr，Grb 10，Rasgrf 1，和Zac 1测定通过逆转录定量聚合酶链反应. ResultsHippocampus转录水平不同产前治疗在男性和女性的性别差异观察Igf 2和Insr的表达。产前EtOH对海马表达的胰岛素途径基因的影响是平行的在体内和体外conditions.ConclusionsThe相似性的基因表达的变化响应产前EtOH之间的体内和体外的条件证明，这些影响已经设置在胎儿海马在GD 18。这加强了离体原代海马培养作为测试和筛选FASD候选药物靶点的工具的可行性。
BackgroundFetal alcohol spectrum disorder (FASD) is the leading nongenetic cause of mental retardation. There are no treatments for FASD to date. Preclinical in vivo and in vitro studies could help in identifying novel drug targets as for other diseases. Here, we describe an ex vivo model that combines the physiological advantages of prenatal ethanol (EtOH) exposure in vivo with the uniformity of primary fetal hippocampal culture to characterize the effects of prenatal EtOH. The insulin signaling pathways are known to be involved in hippocampal functions. Therefore, we compared the expression of insulin signaling pathway genes between fetal hippocampi (in vivo) and primary hippocampal culture (ex vivo). The similarity of prenatal EtOH effects in these 2 paradigms would deem the ex vivo culture acceptable to screen possible treatments for FASD.MethodsPregnant Sprague–Dawley rats received 1 of 3 diets: ad libitum standard laboratory chow (control‐C), isocaloric pair‐fed (nutritional control), and EtOH containing liquid diets from gestational day (GD) 8. Fetal male and female hippocampi were collected either on GD21 (in vivo) or on GD18 for primary culture (ex vivo). Transcript levels ofIgf2,Igf2r,Insr,Grb10,Rasgrf1, andZac1were measured by reverse transcription quantitative polymerase chain reaction.ResultsHippocampal transcript levels differed by prenatal treatment in both males and females with sex differences observed in the expression ofIgf2andInsr. The effect of prenatal EtOH on the hippocampal expression of the insulin pathway genes was parallel in the in vivo and the ex vivo conditions.ConclusionsThe similarity of gene expression changes in response to prenatal EtOH between the in vivo and the ex vivo conditions ascertains that these effects are already set in the fetal hippocampus at GD18. This strengthens the feasibility of the ex vivo primary hippocampal culture as a tool to test and screen candidate drug targets for FASD.
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影响因子：
3.4
作者：
Pressler R;Auvin S
通讯作者：
Auvin S
影响因子：
4.8
作者：
Konkle, Anne T. M.;McCarthy, Margaret M.
通讯作者：
McCarthy, Margaret M.
育龄妇女的饮酒和酗酒情况——美国，2006-2010 年。
DOI：
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发表时间：
2012
期刊：
MMWR. Morbidity and mortality weekly report
影响因子：
--
作者：
Qiang;T. Kanai;A. Kitagawa
通讯作者：
A. Kitagawa
DOI：
10.1126/science.1253533
发表时间：
2014-07-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Yu M;Bardia A;Aceto N;Bersani F;Madden MW;Donaldson MC;Desai R;Zhu H;Comaills V;Zheng Z;Wittner BS;Stojanov P;Brachtel E;Sgroi D;Kapur R;Shioda T;Ting DT;Ramaswamy S;Getz G;Iafrate AJ;Benes C;Toner M;Maheswaran S;Haber DA
通讯作者：
Haber DA
影响因子：
--
作者：
MATHIEU, M;VIGNON, F;ROCHEFORT, H
通讯作者：
ROCHEFORT, H