Strain-specific programming of prenatal ethanol exposure across generations.
Strain-specific programming of prenatal ethanol exposure across generations.
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DOI：
10.1016/j.alcohol.2017.01.002
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发表时间：
2017-05
期刊：
影响因子：
--
通讯作者：
Cameron NM
中科院分区：
文献类型：
--
作者：
Popoola DO;Nizhnikov ME;Cameron NM
产前酒精暴露 (PAE) 的行为后果可以从子宫内暴露的 F1 代遗传给 F2 后代。这种类型的传播受到遗传和表观遗传机制的调节。本研究调查了妊娠第 17-20 天期间产前接触低剂量乙醇（1g/kg）对青春期雄性 F1 和 F2 代两种大鼠的乙醇诱导催眠的代际影响。使用翻正反射丧失（LORR）范例，测试青春期 Long Evans 和 Sprague Dawley 雄性大鼠对 3.5g/kg 或 4.5g/kg 乙醇剂量的乙醇诱导催眠的敏感性。我们假设 PAE 会减弱这两个品系和两代暴露于乙醇的动物对乙醇诱导的催眠的敏感性。有趣的是，我们只在斯普拉格道利大鼠中发现了这种效应。最后，我们研究了 PAE 敏感 Sprague Dawley 菌株大脑皮层中 GABAA 受体 α1、α4 和 δ 亚基表达的 PAE 相关变化。我们假设与对照组动物相比，F1 和 F2 PAE 组大脑皮层 GABAA 受体亚基的表达有所减少。通过蛋白质印迹法定量 F1 和 F2 男性青少年大脑皮层中 GABAA 受体 α1、α4 和 δ 亚基蛋白的表达。 PAE不改变F1代大脑皮质GABAA受体亚基表达，但降低F2代GABAA受体α4和δ亚基表达，并有降低α1亚基表达的趋势。我们还发现了两代中一些亚基之间的相关性。这些与菌株相关的乙醇敏感性脆弱性，以及 PAE 介导的酒精敏感性的代际变化表明，遗传和表观遗传因素相互作用，决定 PAE 动物及其后代的结果。
Behavioral consequences of prenatal alcohol exposure (PAE) can be transmitted from in utero-exposed F1 generation to their F2 offspring. This type of transmission is modulated by genetic and epigenetic mechanism. This study investigated the intergenerational consequences of prenatal exposure to low ethanol dose (1g/kg) during gestational days 17–20, on ethanol-induced hypnosis in adolescent male F1 and F2 generations, in two strains of rats. Adolescent Long Evans and Sprague Dawley male rats were tested for sensitivity to ethanol-induced hypnosis at 3.5g/kg or 4.5g/kg ethanol dose using the loss of righting reflex (LORR) paradigm. We hypothesized that PAE would attenuate sensitivity to ethanol-induced hypnosis in the ethanol-exposed animals in these two strains and in both generations. Interestingly, we only found this effect in Sprague Dawley rats. Lastly, we investigated PAE related changes in expression of GABAA receptor α1, α4, and δ subunits in the cerebral cortex of the PAE sensitive Sprague Dawley strain. We hypothesized a reduction in the cerebral cortex GABAA receptor subunits’ expression in the F1 and F2 PAE groups compared to control animals. GABAA receptor α1, α4, and δ subunits protein expressions were quantified in the cerebral cortex of F1 and F2 male adolescents by western blotting. PAE didn’t alter cerebral cortical GABAA receptor subunit expressions in the F1 generation, but it decreased GABAA receptor α4 and δ subunits’ expressions in the F2 generation, and had a tendency to decrease α1 subunit expression. We also found correlations between some of the subunits in both generations. These strain-dependent vulnerabilities to ethanol sensitivity, and intergenerational PAE-mediated changes in sensitivity to alcohol indicate that genetic and epigenetic factors interact to determine the outcomes of PAE animals and their offspring.
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DOI：
10.1124/jpet.103.049478
发表时间：
2003-06-01
影响因子：
3.5
作者：
Blednov, YA;Walker, D;Harris, RA
通讯作者：
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影响因子：
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DOI：
10.3389/fnevo.2011.00010
发表时间：
2011-01-01
期刊：
Frontiers in evolutionary neuroscience
影响因子：
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作者：
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通讯作者：
Cameron, Nicole M
影响因子：
3.2
作者：
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影响因子：
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