Springer US
New York
Springer
http://www.springer-ny.com
12035
10.1007/12035.1559-1182
0893-7648
1559-1182
Molecular Neurobiology
Mol Neurobiol
Biomedicine
Neurosciences
Neurobiology
Cell Biology
Neurology
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65
2017
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2017
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2017
Springer Science+Business Media New York
2017
9680
10.1007/s12035-015-9680-6
23
SK3 Channel Overexpression in Mice Causes Hippocampal Shrinkage Associated with Cognitive Impairments
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1091
2015
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The Author(s)
2016
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Sabine
Martin
Marcio
Lazzarini
Christian
Dullin
Saju
Balakrishnan
Felipe
V.
Gomes
Milena
Ninkovic
Ahmed
El
Hady
Luis
A.
Pardo
Walter
Stühmer
+49 551 3899646
stuehmer@em.mpg.de
Elaine
Del-Bel
+55 16 36024047
eadelbel@forp.usp.br
Department of Molecular Biology of Neuronal Signals
Max Planck Institute of Experimental Medicine
Hermann-Rein-Strasse 3
37075
Göttingen
Germany
Center Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)
Göttingen
Germany
Department of Diagnostic and Interventional Radiology
Georg-August University Medical Center
37075
Göttingen
Germany
Department of Neuro- and Sensory Physiology
Georg-August University Medical Center
37073
Göttingen
Germany
Department of Pharmacology, Medical School of Ribeirão Preto
University of São Paulo
14040-900
Ribeirão Preto
Brazil
Department of Neurosurgery
Georg-August University Medical Center
37075
Göttingen
Germany
Bernstein Focus for Neurotechnology and Bernstein Center for Computational Neuroscience
Göttingen
Germany
Theoretical Neurophysics, Department of Non-linear Dynamics
Max Planck Institute for Dynamics and Self-Organization
37077
Göttingen
Germany
The Interdisciplinary Collaborative Research Center 889 “Cellular Mechanisms of Sensory Processing”
Göttingen
Germany
Oncophysiology Group
Max Planck Institute of Experimental Medicine
37075
Göttingen
Germany
Department of Morphology, Physiology and Pathology, CNPQ Research 1B (Biophysics, Biochemistry, Pharmacology and Neuroscience)
University of São Paulo Dental School of Ribeirão Preto
Avenida do Café 3400
14040-904
Ribeirão Preto
Brazil
Abstract
The dysfunction of the small-conductance calcium-activated K+ channel SK3 has been described as one of the factors responsible for the progress of psychoneurological diseases, but the molecular basis of this is largely unknown. This report reveals through use of immunohistochemistry and computational tomography that long-term increased expression of the SK3 small-conductance calcium-activated potassium channel (SK3-T/T) in mice induces a notable bilateral reduction of the hippocampal area (more than 50 %). Histological analysis showed that SK3-T/T mice have cellular disarrangements and neuron discontinuities in the hippocampal formation CA1 and CA3 neuronal layer. SK3 overexpression resulted in cognitive loss as determined by the object recognition test. Electrophysiological examination of hippocampal slices revealed that SK3 channel overexpression induced deficiency of long-term potentiation in hippocampal microcircuits. In association with these results, there were changes at the mRNA levels of some genes involved in Alzheimer’s disease and/or linked to schizophrenia, epilepsy, and autism. Taken together, these features suggest that augmenting the function of SK3 ion channel in mice may present a unique opportunity to investigate the neural basis of central nervous system dysfunctions associated with schizophrenia, Alzheimer’s disease, or other neuropsychiatric/neurodegenerative disorders in this model system. As a more detailed understanding of the role of the SK3 channel in brain disorders is limited by the lack of specific SK3 antagonists and agonists, the results observed in this study are of significant interest; they suggest a new approach for the development of neuroprotective strategies in neuropsychiatric/neurodegenerative diseases with SK3 representing a potential drug target.
Keywords
Potassium channel KCa2.3
Learning and memory
Whole-cell patch clamp
Schizophrenia
Alzheimer’s disease
Sabine Martin and Marcio Lazzarini contributed equally to this work.
Electronic supplementary material
The online version of this article (doi:
10.1007/s12035-015-9680-6
) contains supplementary material, which is available to authorized users.