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Insulin-like growth factor-2 does not improve behavioral deficits in mouse and rat models of Angelman Syndrome
BACKGROUND: Angelman Syndrome (AS) is a rare neurodevelopmental disorder for which there is currently no cure or effective therapeutic. Since the genetic cause of AS is known to be dysfunctional expression of the maternal allele of ubiquitin protein ligase E3A (UBE3A), several genetic animal models...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444390/ https://www.ncbi.nlm.nih.gov/pubmed/34526125 http://dx.doi.org/10.1186/s13229-021-00467-1 |
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author | Berg, Elizabeth L. Petkova, Stela P. Born, Heather A. Adhikari, Anna Anderson, Anne E. Silverman, Jill L. |
author_facet | Berg, Elizabeth L. Petkova, Stela P. Born, Heather A. Adhikari, Anna Anderson, Anne E. Silverman, Jill L. |
author_sort | Berg, Elizabeth L. |
collection | PubMed |
description | BACKGROUND: Angelman Syndrome (AS) is a rare neurodevelopmental disorder for which there is currently no cure or effective therapeutic. Since the genetic cause of AS is known to be dysfunctional expression of the maternal allele of ubiquitin protein ligase E3A (UBE3A), several genetic animal models of AS have been developed. Both the Ube3a maternal deletion mouse and rat models of AS reliably demonstrate behavioral phenotypes of relevance to AS and therefore offer suitable in vivo systems in which to test potential therapeutics. One promising candidate treatment is insulin-like growth factor-2 (IGF-2), which has recently been shown to ameliorate behavioral deficits in the mouse model of AS and improve cognitive abilities across model systems. METHODS: We used both the Ube3a maternal deletion mouse and rat models of AS to evaluate the ability of IGF-2 to improve electrophysiological and behavioral outcomes. RESULTS: Acute systemic administration of IGF-2 had an effect on electrophysiological activity in the brain and on a metric of motor ability; however the effects were not enduring or extensive. Additional metrics of motor behavior, learning, ambulation, and coordination were unaffected and IGF-2 did not improve social communication, seizure threshold, or cognition. LIMITATIONS: The generalizability of these results to humans is difficult to predict and it remains possible that dosing schemes (i.e., chronic or subchronic dosing), routes, and/or post-treatment intervals other than that used herein may show more efficacy. CONCLUSIONS: Despite a few observed effects of IGF-2, our results taken together indicate that IGF-2 treatment does not profoundly improve behavioral deficits in mouse or rat models of AS. These findings shed cautionary light on the potential utility of acute systemic IGF-2 administration in the treatment of AS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13229-021-00467-1. |
format | Online Article Text |
id | pubmed-8444390 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-84443902021-09-16 Insulin-like growth factor-2 does not improve behavioral deficits in mouse and rat models of Angelman Syndrome Berg, Elizabeth L. Petkova, Stela P. Born, Heather A. Adhikari, Anna Anderson, Anne E. Silverman, Jill L. Mol Autism Research BACKGROUND: Angelman Syndrome (AS) is a rare neurodevelopmental disorder for which there is currently no cure or effective therapeutic. Since the genetic cause of AS is known to be dysfunctional expression of the maternal allele of ubiquitin protein ligase E3A (UBE3A), several genetic animal models of AS have been developed. Both the Ube3a maternal deletion mouse and rat models of AS reliably demonstrate behavioral phenotypes of relevance to AS and therefore offer suitable in vivo systems in which to test potential therapeutics. One promising candidate treatment is insulin-like growth factor-2 (IGF-2), which has recently been shown to ameliorate behavioral deficits in the mouse model of AS and improve cognitive abilities across model systems. METHODS: We used both the Ube3a maternal deletion mouse and rat models of AS to evaluate the ability of IGF-2 to improve electrophysiological and behavioral outcomes. RESULTS: Acute systemic administration of IGF-2 had an effect on electrophysiological activity in the brain and on a metric of motor ability; however the effects were not enduring or extensive. Additional metrics of motor behavior, learning, ambulation, and coordination were unaffected and IGF-2 did not improve social communication, seizure threshold, or cognition. LIMITATIONS: The generalizability of these results to humans is difficult to predict and it remains possible that dosing schemes (i.e., chronic or subchronic dosing), routes, and/or post-treatment intervals other than that used herein may show more efficacy. CONCLUSIONS: Despite a few observed effects of IGF-2, our results taken together indicate that IGF-2 treatment does not profoundly improve behavioral deficits in mouse or rat models of AS. These findings shed cautionary light on the potential utility of acute systemic IGF-2 administration in the treatment of AS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13229-021-00467-1. BioMed Central 2021-09-15 /pmc/articles/PMC8444390/ /pubmed/34526125 http://dx.doi.org/10.1186/s13229-021-00467-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Berg, Elizabeth L. Petkova, Stela P. Born, Heather A. Adhikari, Anna Anderson, Anne E. Silverman, Jill L. Insulin-like growth factor-2 does not improve behavioral deficits in mouse and rat models of Angelman Syndrome |
title | Insulin-like growth factor-2 does not improve behavioral deficits in mouse and rat models of Angelman Syndrome |
title_full | Insulin-like growth factor-2 does not improve behavioral deficits in mouse and rat models of Angelman Syndrome |
title_fullStr | Insulin-like growth factor-2 does not improve behavioral deficits in mouse and rat models of Angelman Syndrome |
title_full_unstemmed | Insulin-like growth factor-2 does not improve behavioral deficits in mouse and rat models of Angelman Syndrome |
title_short | Insulin-like growth factor-2 does not improve behavioral deficits in mouse and rat models of Angelman Syndrome |
title_sort | insulin-like growth factor-2 does not improve behavioral deficits in mouse and rat models of angelman syndrome |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444390/ https://www.ncbi.nlm.nih.gov/pubmed/34526125 http://dx.doi.org/10.1186/s13229-021-00467-1 |
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