Chronic α1-Na/K-ATPase inhibition reverses the elongation of the axon initial segment of the hippocampal CA1 pyramidal neurons in Angelman syndrome model mice

被引:8
作者
Rayi, Prudhvi Raj [1 ]
Bagrov, Alexei Y. [2 ]
Kaphzan, Hanoch [1 ]
机构
[1] Univ Haifa, Sagol Dept Neurobiol, Integrated Brain & Behav Res Ctr, IL-3498838 Haifa, Israel
[2] Sechenov Inst Evolutionary Physiol & Biochem, St Petersburg 194223, Russia
基金
以色列科学基金会;
关键词
ACTIVITY-DEPENDENT RELOCATION; ACTION-POTENTIAL INITIATION; MOUSE MODEL; AFTER-HYPERPOLARIZATION; STRUCTURAL PLASTICITY; PRADER-WILLI; NA/K-ATPASE; K+ CHANNELS; UBE3A; EXCITABILITY;
D O I
10.1038/s41386-020-00907-1
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Angelman syndrome (AS) is a neurodevelopmental disorder caused by the loss of function of the maternal UBE3A gene. The hippocampus is one of the most prominently affected brain regions in AS model mice, manifesting in severe hippocampal-dependent memory and plasticity deficits. Previous studies in AS mice reported an elongated axon initial segment (AIS) in pyramidal neurons (PNs) of the hippocampal CA1 region. These were the first reports in mammals to show AIS elongation in vivo. Correspondingly, this AIS elongation was linked to enhanced expression of the alpha 1 subunit of Na+/K+-ATPase (alpha 1-NaKA). Recently, it was shown that selective pharmacological inhibition of alpha 1-NaKA by marinobufagenin (MBG) in adult AS mice rescued the hippocampal-dependent deficits via normalizing their compromised activity-dependent calcium (Ca+2) dynamics. In the herein study, we showed that a chronic selective alpha 1-NaKA inhibition reversed the AIS elongation in hippocampal CA1 PNs of adult AS mice, and differentially altered their excitability and intrinsic properties. Taken together, our study is the first to demonstrate in vivo structural plasticity of the AIS in a mammalian model, and further elaborates on the modulatory effects of elevated alpha 1-NaKA levels in the hippocampus of AS mice.
引用
收藏
页码:654 / 664
页数:11
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