美国儿童国立医院Kazue Hashimoto-Torii、Masaaki Torii以及美国宾夕法尼亚州立大学医学院Yuka Imamura Kawasawa研究组合作取得一项新突破。他们的最新研究发现阻断Kcnn2可回复小鼠缺陷的胎儿酒精谱系障碍（FASD）模型中的学习缺陷。这一研究成果于2020年3月16日发表在《自然-神经科学》杂志上。

他们表示对祖细胞中酒精的急性反应改变了其后代神经元的基因表达。在改变的基因中，运动皮质中钙激活的钾离子通道Kcnn2的增加与FASD模型小鼠运动学习障碍有关。Kcnn2的药理学阻断剂可改善这些学习缺陷，表明Kcnn2阻断剂可作为FASD学习障碍的一种新干预手段。

据了解，学习障碍是产前接触有害物质而引起的先天性疾病的标志。这些包括具有广泛认知FASD，包括运动技能开发受损。尽管已经很好地鉴定了这些作用，但是导致这些行为后果的分子作用仍待确定。他们先前发现，胚胎脑中对酒精的急性分子反应是随机的，在神经祖细胞之间也是不同的。然而，由这些异质性反应引起的病理生理后果仍然未知。

附：英文原文

Title: Kcnn2 blockade reverses learning deficits in a mouse model of fetal alcohol spectrum disorders

Author: Shahid Mohammad, Stephen J. Page, Li Wang, Seiji Ishii, Peijun Li, Toru Sasaki, Aiesha Basha, Anna Salzberg, Zenaide Quezado, Fumiaki Imamura, Hirotaka Nishi, Keiichi Isaka, Joshua G. Corbin, Judy S. Liu, Yuka Imamura Kawasawa, Masaaki Torii, Kazue Hashimoto-Torii

Issue&Volume: 2020-03-16

Abstract: 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.

DOI: 10.1038/s41593-020-0592-z

Source: https://www.nature.com/articles/s41593-020-0592-z