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Characterization of Cognitive Deficits in Mice With an Alternating Hemiplegia-Linked Mutation

Cognitive impairment is a prominent feature in a range of different movement disorders. Children with Alternating Hemiplegia of Childhood are prone to developmental delay, with deficits in cognitive functioning becoming progressively more evident as they grow older. Heterozygous mutations of the ATP...

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Autores principales: Kirshenbaum, Greer S., Dachtler, James, Roder, John C., Clapcote, Steven J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Psychological Association 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4655871/
https://www.ncbi.nlm.nih.gov/pubmed/26501181
http://dx.doi.org/10.1037/bne0000097
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author Kirshenbaum, Greer S.
Dachtler, James
Roder, John C.
Clapcote, Steven J.
author_facet Kirshenbaum, Greer S.
Dachtler, James
Roder, John C.
Clapcote, Steven J.
author_sort Kirshenbaum, Greer S.
collection PubMed
description Cognitive impairment is a prominent feature in a range of different movement disorders. Children with Alternating Hemiplegia of Childhood are prone to developmental delay, with deficits in cognitive functioning becoming progressively more evident as they grow older. Heterozygous mutations of the ATP1A3 gene, encoding the Na(+),K(+)-ATPase α3 subunit, have been identified as the primary cause of Alternating Hemiplegia. Heterozygous Myshkin mice have an amino acid change (I810N) in Na(+),K(+)-ATPase α3 that is also found in Alternating Hemiplegia. To investigate whether Myshkin mice exhibit learning and memory deficits resembling the cognitive impairments of patients with Alternating Hemiplegia, we subjected them to a range of behavioral tests that interrogate various cognitive domains. Myshkin mice showed impairments in spatial memory, spatial habituation, locomotor habituation, object recognition, social recognition, and trace fear conditioning, as well as in the visible platform version of the Morris water maze. Increasing the duration of training ameliorated the deficit in social recognition but not in spatial habituation. The deficits of Myshkin mice in all of the learning and memory tests used are consistent with the cognitive impairment of the vast majority of AHC patients. These mice could thus help advance our understanding of the underlying neural mechanisms influencing cognitive impairment in patients with ATP1A3-related disorders.
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spelling pubmed-46558712015-12-02 Characterization of Cognitive Deficits in Mice With an Alternating Hemiplegia-Linked Mutation Kirshenbaum, Greer S. Dachtler, James Roder, John C. Clapcote, Steven J. Behav Neurosci Articles Cognitive impairment is a prominent feature in a range of different movement disorders. Children with Alternating Hemiplegia of Childhood are prone to developmental delay, with deficits in cognitive functioning becoming progressively more evident as they grow older. Heterozygous mutations of the ATP1A3 gene, encoding the Na(+),K(+)-ATPase α3 subunit, have been identified as the primary cause of Alternating Hemiplegia. Heterozygous Myshkin mice have an amino acid change (I810N) in Na(+),K(+)-ATPase α3 that is also found in Alternating Hemiplegia. To investigate whether Myshkin mice exhibit learning and memory deficits resembling the cognitive impairments of patients with Alternating Hemiplegia, we subjected them to a range of behavioral tests that interrogate various cognitive domains. Myshkin mice showed impairments in spatial memory, spatial habituation, locomotor habituation, object recognition, social recognition, and trace fear conditioning, as well as in the visible platform version of the Morris water maze. Increasing the duration of training ameliorated the deficit in social recognition but not in spatial habituation. The deficits of Myshkin mice in all of the learning and memory tests used are consistent with the cognitive impairment of the vast majority of AHC patients. These mice could thus help advance our understanding of the underlying neural mechanisms influencing cognitive impairment in patients with ATP1A3-related disorders. American Psychological Association 2015-10-26 2015-12 /pmc/articles/PMC4655871/ /pubmed/26501181 http://dx.doi.org/10.1037/bne0000097 Text en © 2015 The Author(s) http://creativecommons.org/licenses/by/3.0/ This article has been published under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright for this article is retained by the author(s). Author(s) grant(s) the American Psychological Association the exclusive right to publish the article and identify itself as the original publisher.
spellingShingle Articles
Kirshenbaum, Greer S.
Dachtler, James
Roder, John C.
Clapcote, Steven J.
Characterization of Cognitive Deficits in Mice With an Alternating Hemiplegia-Linked Mutation
title Characterization of Cognitive Deficits in Mice With an Alternating Hemiplegia-Linked Mutation
title_full Characterization of Cognitive Deficits in Mice With an Alternating Hemiplegia-Linked Mutation
title_fullStr Characterization of Cognitive Deficits in Mice With an Alternating Hemiplegia-Linked Mutation
title_full_unstemmed Characterization of Cognitive Deficits in Mice With an Alternating Hemiplegia-Linked Mutation
title_short Characterization of Cognitive Deficits in Mice With an Alternating Hemiplegia-Linked Mutation
title_sort characterization of cognitive deficits in mice with an alternating hemiplegia-linked mutation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4655871/
https://www.ncbi.nlm.nih.gov/pubmed/26501181
http://dx.doi.org/10.1037/bne0000097
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