A Drosophila model for fetal alcohol syndrome disorders: role for the insulin pathway.
A Drosophila model for fetal alcohol syndrome disorders: role for the insulin pathway.
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DOI：
10.1242/dmm.006411
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发表时间：
2011-05
影响因子：
4.3
通讯作者：
Heberlein U
中科院分区：
文献类型：
--
作者：
McClure KD;French RL;Heberlein U
人类产前暴露于乙醇会导致广泛的发育异常，包括生长缺陷、发育迟缓、大脑体积缩小、永久性神经行为异常和胎儿死亡。在这里，我们描述了使用果蝇作为模型，探索乙醇暴露对发展和行为的影响。我们发现，发育乙醇暴露导致生存能力降低，发育迟缓和成年体型缩小。我们发现用含乙醇食物饲养的果蝇的大脑和成虫盘较小，这是由于细胞分裂减少而不是细胞凋亡增加。此外，我们表明，在哺乳动物中，在乙醇上饲养的苍蝇改变了响应乙醇蒸汽暴露的成年人，包括增加运动激活，耐药的镇静作用的药物和减少耐受性的发展后，反复乙醇暴露。我们已经发现，发育和行为缺陷主要是由于乙醇对胰岛素信号传导的影响;特别是，果蝇胰岛素样肽（Dilp）和胰岛素受体表达的减少。Dilp蛋白在幼虫脑中的转基因表达抑制了乙醇饲养的成年苍蝇所显示的发育和行为异常。因此，我们的研究结果建立果蝇作为一个有用的模型系统，以揭示胎儿酒精综合征的复杂病因。
Prenatal exposure to ethanol in humans results in a wide range of developmental abnormalities, including growth deficiency, developmental delay, reduced brain size, permanent neurobehavioral abnormalities and fetal death. Here we describe the use of Drosophila melanogaster as a model for exploring the effects of ethanol exposure on development and behavior. We show that developmental ethanol exposure causes reduced viability, developmental delay and reduced adult body size. We find that flies reared on ethanol-containing food have smaller brains and imaginal discs, which is due to reduced cell division rather than increased apoptosis. Additionally, we show that, as in mammals, flies reared on ethanol have altered responses to ethanol vapor exposure as adults, including increased locomotor activation, resistance to the sedating effects of the drug and reduced tolerance development upon repeated ethanol exposure. We have found that the developmental and behavioral defects are largely due to the effects of ethanol on insulin signaling; specifically, a reduction in Drosophila insulin-like peptide (Dilp) and insulin receptor expression. Transgenic expression of Dilp proteins in the larval brain suppressed both the developmental and behavioral abnormalities displayed by ethanol-reared adult flies. Our results thus establish Drosophila as a useful model system to uncover the complex etiology of fetal alcohol syndrome.
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影响因子：
2.7
作者：
Blader, P;Strähle, U
通讯作者：
Strähle, U
影响因子：
9.2
作者：
Brogiolo, W;Stocker, H;Hafen, E
通讯作者：
Hafen, E
影响因子：
3.7
作者：
Kong EC;Woo K;Li H;Lebestky T;Mayer N;Sniffen MR;Heberlein U;Bainton RJ;Hirsh J;Wolf FW
通讯作者：
Wolf FW
影响因子：
5.1
作者：
CLARREN, SK;ASTLEY, SJ;SPELLMAN, D
通讯作者：
SPELLMAN, D
影响因子：
5.1
作者：
CHRISTOFFEL, KK;SALAFSKY, I
通讯作者：
SALAFSKY, I