Hippocampus-dependent memory and allele-specific gene expression in adult offspring of alcohol-consuming dams after neonatal treatment with thyroxin or metformin.
Hippocampus-dependent memory and allele-specific gene expression in adult offspring of alcohol-consuming dams after neonatal treatment with thyroxin or metformin.
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新生儿用甲状腺素或二甲双胍治疗后，酗酒大坝的成年后代的海马依赖性记忆和等位基因特异性基因表达。
DOI：
10.1038/mp.2017.129
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发表时间：
2018-07
影响因子：
11
通讯作者：
Redei EE
中科院分区：
文献类型：
--
作者：
Tunc-Ozcan E;Wert SL;Lim PH;Ferreira A;Redei EE
胎儿酒精谱系障碍（FASD）是胎儿酒精暴露（FAE）的结果，影响全球2-11%的儿童，没有有效的治疗方法。基于海马的学习和记忆缺陷是FASD的主要症状。我们先前的研究显示饮酒的孕鼠会出现低甲状腺素血症和高血糖，可能会影响胎儿的神经发育。我们给予车辆，甲状腺素（T4）或二甲双胍的新生大鼠后FAE和大鼠在海马依赖的上下文恐惧条件化范式在成年期进行了测试。T4和二甲双胍均缓解FAE诱导的情境恐惧记忆缺陷，并逆转甲状腺素失活酶、脱碘酶-III（Dio 3）和胰岛素样生长因子2（Igf 2）的海马表达变化，这些基因已知可调节记忆过程。新生儿T4恢复了成年男性海马中印迹Dio 3和Igf 2的母体等位基因表达，而二甲双胍仅恢复了FAE引起的Igf 2表达变化。海马DNA甲基转移酶1（Dnmt 1）的表达减少，在发育过程中维持Dio 3和Igf 2的印记，通过两种治疗方法进行了标准化。给予Dnmt 1抑制剂对照新生儿导致恐惧记忆和海马Igf 2等位基因特异性表达的FAE样缺陷，二甲双胍可逆转。我们认为新生儿FAE后给予T4和二甲双胍通过升高Dnmt 1从而使成年后代海马Dio 3和Igf 2表达正常化来影响记忆。目前的结果表明，T4和二甲双胍，在新生儿期（相当于人类妊娠晚期）给药，是FASD的潜在治疗方法，也可以想象是其他神经发育障碍伴认知缺陷的治疗方法。
Fetal alcohol spectrum disorder (FASD), the result of fetal alcohol exposure (FAE), affects 2–11% of children worldwide, with no effective treatments. Hippocampus-based learning and memory deficits are key symptoms of FASD. Our previous studies show hypothyroxinemia and hyperglycemia of the alcohol-consuming pregnant rat, which likely affects fetal neurodevelopment. We administered vehicle, thyroxine (T4) or metformin to neonatal rats post-FAE and rats were tested in the hippocampus dependent contextual fear-conditioning paradigm in adulthood. Both T4 and metformin alleviated contextual fear memory deficit induced by FAE, and reversed the hippocampal expression changes in the thyroid hormone-inactivating enzyme, deiodinase-III (Dio3) and insulin-like growth factor 2 (Igf2), genes that are known to modulate memory processes. Neonatal T4 restored maternal allelic expressions of the imprinted Dio3 and Igf2 in the adult male hippocampus, while metformin restored FAE-caused changes in Igf2 expression only. The decreased hippocampal expression of DNA methyltransferase 1 (Dnmt1), that maintains the imprinting of Dio3 and Igf2 during development, was normalized by both treatments. Administering Dnmt1 inhibitor to control neonates resulted in FAE-like deficits in fear memory and hippocampal allele-specific expression of Igf2, which were reversed by metformin. We propose that neonatal administration of T4 and metformin post-FAE affect memory via elevating Dnmt1 and consequently normalizing hippocampal Dio3 and Igf2 expressions in the adult offspring. The present results indicate that T4 and metformin, administered during the neonatal period that is equivalent to the third trimester of human pregnancy, are potential treatments for FASD and conceivably for other neurodevelopmental disorders with cognitive deficits.
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产前酒精暴露后小鼠 Igf2 基因座 DNA 甲基化和基因表达略有下降：甲基补充饮食的影响。
影响因子：
2.3
作者：
Downing, Chris;Johnson, Thomas E.;Larson, Colin;Leakey, Tatiana I.;Siegfried, Rachel N.;Rafferty, Tonya M.;Cooney, Craig A.
通讯作者：
Cooney, Craig A.
Dnmt1 和 Dnmt3a 维持 DNA 甲基化并调节成人前脑神经元的突触功能
影响因子：
25
作者：
Feng, Jian;Zhou, Yu;Campbell, Susan L.;Le, Thuc;Li, En;Sweatt, J. David;Silva, Alcino J.;Fan, Guoping
通讯作者：
Fan, Guoping
DOI：
10.1017/s1355617713001343
发表时间：
2014-02-01
影响因子：
2.6
作者：
Dudek, Joanna;Skocic, Jovanka;Rovet, Joanne
通讯作者：
Rovet, Joanne
影响因子：
4.6
作者：
Harper, Kathryn M.;Tunc-Ozcan, Elif;Redei, Eva E.
通讯作者：
Redei, Eva E.
DOI：
10.1111/acer.12082
发表时间：
2013-07
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Bekdash RA;Zhang C;Sarkar DK
通讯作者：
Sarkar DK