Genetic Reduction of the α1 Subunit of Na/K-ATPase Corrects Multiple Hippocampal Phenotypes in Angelman Syndrome
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...
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doaj-ae88ddab47534501ac57a81888e0612f2020-11-24T22:03:23ZengElsevierCell Reports2211-12472013-08-014340541210.1016/j.celrep.2013.07.005Genetic Reduction of the α1 Subunit of Na/K-ATPase Corrects Multiple Hippocampal Phenotypes in Angelman SyndromeHanoch Kaphzan0Shelly A. Buffington1Akila B. Ramaraj2Jerry B. Lingrel3Matthew N. Rasband4Emanuela Santini5Eric Klann6Center for Neural Science, New York University, New York, NY 10003, USADepartment of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USACenter for Neural Science, New York University, New York, NY 10003, USADepartment of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, Cincinnati, OH 45267, USADepartment of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USACenter for Neural Science, New York University, New York, NY 10003, USACenter for Neural Science, New York University, New York, NY 10003, USA 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. http://www.sciencedirect.com/science/article/pii/S2211124713003525 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hanoch Kaphzan Shelly A. Buffington Akila B. Ramaraj Jerry B. Lingrel Matthew N. Rasband Emanuela Santini Eric Klann |
spellingShingle |
Hanoch Kaphzan Shelly A. Buffington Akila B. Ramaraj Jerry B. Lingrel Matthew N. Rasband Emanuela Santini Eric Klann Genetic Reduction of the α1 Subunit of Na/K-ATPase Corrects Multiple Hippocampal Phenotypes in Angelman Syndrome Cell Reports |
author_facet |
Hanoch Kaphzan Shelly A. Buffington Akila B. Ramaraj Jerry B. Lingrel Matthew N. Rasband Emanuela Santini Eric Klann |
author_sort |
Hanoch Kaphzan |
title |
Genetic Reduction of the α1 Subunit of Na/K-ATPase Corrects Multiple Hippocampal Phenotypes in Angelman Syndrome |
title_short |
Genetic Reduction of the α1 Subunit of Na/K-ATPase Corrects Multiple Hippocampal Phenotypes in Angelman Syndrome |
title_full |
Genetic Reduction of the α1 Subunit of Na/K-ATPase Corrects Multiple Hippocampal Phenotypes in Angelman Syndrome |
title_fullStr |
Genetic Reduction of the α1 Subunit of Na/K-ATPase Corrects Multiple Hippocampal Phenotypes in Angelman Syndrome |
title_full_unstemmed |
Genetic Reduction of the α1 Subunit of Na/K-ATPase Corrects Multiple Hippocampal Phenotypes in Angelman Syndrome |
title_sort |
genetic reduction of the α1 subunit of na/k-atpase corrects multiple hippocampal phenotypes in angelman syndrome |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2013-08-01 |
description |
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.
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url |
http://www.sciencedirect.com/science/article/pii/S2211124713003525 |
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