Center for Neural Science, New York University, New York, NY 10003, USA.
Cell Rep. 2013 Aug 15;4(3):405-12. doi: 10.1016/j.celrep.2013.07.005. Epub 2013 Aug 1.
Angelman syndrome (AS) is associated with symptoms that include autism, intellectual disability, motor abnormalities, and epilepsy. We recently showed that AS model mice have increased expression of the alpha1 subunit of Na/K-ATPase (α1-NaKA) in the hippocampus, which was correlated with increased expression of axon initial segment (AIS) proteins. Our developmental analysis revealed that the increase in α1-NaKA expression preceded that of the AIS proteins. Therefore, we hypothesized that α1-NaKA overexpression drives AIS abnormalities and that by reducing its expression these and other phenotypes could be corrected in AS model mice. Herein, we report that the genetic normalization of α1-NaKA levels in AS model mice corrects multiple hippocampal phenotypes, including alterations in the AIS, aberrant intrinsic membrane properties, impaired synaptic plasticity, and memory deficits. These findings strongly suggest that increased expression of α1-NaKA plays an important role in a broad range of abnormalities in the hippocampus of AS model mice.
天使综合征（AS）与自闭症、智力障碍、运动异常和癫痫等症状相关。我们最近发现，AS 模型小鼠的海马体中 Na/K-ATPase 的 α1 亚基（α1-NaKA）表达增加，这与轴突起始段（AIS）蛋白的表达增加有关。我们的发育分析表明，α1-NaKA 表达的增加先于 AIS 蛋白的增加。因此，我们假设 α1-NaKA 的过表达导致 AIS 异常，并且通过降低其表达，可以纠正 AS 模型小鼠中的这些和其他表型。在此，我们报告称，AS 模型小鼠中 α1-NaKA 水平的遗传正常化纠正了多种海马体表型，包括 AIS 的改变、异常的内在膜特性、突触可塑性受损和记忆缺陷。这些发现强烈表明，α1-NaKA 的表达增加在 AS 模型小鼠的海马体中广泛存在的多种异常中发挥着重要作用。
