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Kcnn2 blockade reverses learning deficits in a mouse model of fetal alcohol spectrum disorders.
Nature Neuroscience ( IF 21.2 ) Pub Date : 2020-03-16 , DOI: 10.1038/s41593-020-0592-z
Shahid Mohammad 1 , Stephen J Page 1 , Li Wang 1 , Seiji Ishii 1 , Peijun Li 1, 2 , Toru Sasaki 1, 3 , Aiesha Basha 1 , Anna Salzberg 4 , Zenaide Quezado 5 , Fumiaki Imamura 4 , Hirotaka Nishi 3 , Keiichi Isaka 3 , Joshua G Corbin 1, 6 , Judy S Liu 7 , Yuka Imamura Kawasawa 4, 8 , Masaaki Torii 1, 6 , Kazue Hashimoto-Torii 1, 6
Affiliation  

Learning disabilities are hallmarks of congenital conditions caused by prenatal exposure to harmful agents. These include fetal alcohol spectrum disorders (FASDs) with a wide range of cognitive deficiencies, including impaired motor skill development. Although these effects have been well characterized, the molecular effects that bring about these behavioral consequences remain to be determined. We previously found that the acute molecular responses to alcohol in the embryonic brain are stochastic, varying among neural progenitor cells. However, the pathophysiological consequences stemming from these heterogeneous responses remain unknown. Here we show that acute responses to alcohol in progenitor cells altered gene expression in their descendant neurons. Among the altered genes, an increase of the calcium-activated potassium channel Kcnn2 in the motor cortex correlated with motor learning deficits in a mouse model of FASD. Pharmacologic blockade of Kcnn2 improves these learning deficits, suggesting Kcnn2 blockers as a new intervention for learning disabilities in FASD.

中文翻译:

Kcnn2 阻断可逆转胎儿酒精谱系障碍小鼠模型中的学习缺陷。

学习障碍是产前接触有害物质引起的先天性疾病的标志。这些包括具有广泛认知缺陷的胎儿酒精谱系障碍 (FASD),包括运动技能发展受损。尽管这些影响已得到很好的表征,但导致这些行为后果的分子效应仍有待确定。我们之前发现胚胎大脑中对酒精的急性分子反应是随机的,在神经祖细胞中有所不同。然而,源自这些异质反应的病理生理学后果仍然未知。在这里,我们表明祖细胞对酒精的急性反应改变了其后代神经元中的基因表达。在改变的基因中,运动皮层中钙激活钾通道 Kcnn2 的增加与 FASD 小鼠模型中的运动学习缺陷相关。Kcnn2 的药理学阻断改善了这些学习缺陷,表明 Kcnn2 阻断剂作为 FASD 学习障碍的新干预措施。
更新日期:2020-03-16
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