Cargando…
R-Baclofen Reverses Cognitive Deficits and Improves Social Interactions in Two Lines of 16p11.2 Deletion Mice
Human chromosome 16p11.2 microdeletion is among the most common gene copy number variations (CNVs) known to confer risk for intellectual disability (ID) and autism spectrum disorder (ASD) and affects an estimated 3 in 10 000 people. Caused by a single copy deletion of ~27 genes, 16p11.2 microdeletio...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770771/ https://www.ncbi.nlm.nih.gov/pubmed/28984295 http://dx.doi.org/10.1038/npp.2017.236 |
_version_ | 1783293130496278528 |
---|---|
author | Stoppel, Laura J Kazdoba, Tatiana M Schaffler, Melanie D Preza, Anthony R Heynen, Arnold Crawley, Jacqueline N Bear, Mark F |
author_facet | Stoppel, Laura J Kazdoba, Tatiana M Schaffler, Melanie D Preza, Anthony R Heynen, Arnold Crawley, Jacqueline N Bear, Mark F |
author_sort | Stoppel, Laura J |
collection | PubMed |
description | Human chromosome 16p11.2 microdeletion is among the most common gene copy number variations (CNVs) known to confer risk for intellectual disability (ID) and autism spectrum disorder (ASD) and affects an estimated 3 in 10 000 people. Caused by a single copy deletion of ~27 genes, 16p11.2 microdeletion syndrome is characterized by ID, impaired language, communication and socialization skills, and ASD. Studies in animal models where a single copy of the syntenic 16p11.2 region has been deleted have revealed morphological, behavioral, and electrophysiological abnormalities. Previous studies suggested the possibility of some overlap in the mechanisms of pathophysiology in 16p11.2 microdeletion syndrome and fragile X syndrome. Improvements in fragile X phenotypes have been observed following chronic treatment with R-baclofen, a selective agonist of GABA(B) receptors. We were therefore motivated to investigate the effects of chronic oral R-baclofen administration in two independently generated mouse models of 16p11.2 microdeletion syndrome. In studies performed across two independent laboratories, we found that chronic activation of GABA(B) receptors improved performance on a series of cognitive and social tasks known to be impaired in two different 16p11.2 deletion mouse models. Our findings suggest that R-baclofen may have clinical utility for some of the core symptoms of human 16p11.2 microdeletion syndrome. |
format | Online Article Text |
id | pubmed-5770771 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-57707712018-02-01 R-Baclofen Reverses Cognitive Deficits and Improves Social Interactions in Two Lines of 16p11.2 Deletion Mice Stoppel, Laura J Kazdoba, Tatiana M Schaffler, Melanie D Preza, Anthony R Heynen, Arnold Crawley, Jacqueline N Bear, Mark F Neuropsychopharmacology Original Article Human chromosome 16p11.2 microdeletion is among the most common gene copy number variations (CNVs) known to confer risk for intellectual disability (ID) and autism spectrum disorder (ASD) and affects an estimated 3 in 10 000 people. Caused by a single copy deletion of ~27 genes, 16p11.2 microdeletion syndrome is characterized by ID, impaired language, communication and socialization skills, and ASD. Studies in animal models where a single copy of the syntenic 16p11.2 region has been deleted have revealed morphological, behavioral, and electrophysiological abnormalities. Previous studies suggested the possibility of some overlap in the mechanisms of pathophysiology in 16p11.2 microdeletion syndrome and fragile X syndrome. Improvements in fragile X phenotypes have been observed following chronic treatment with R-baclofen, a selective agonist of GABA(B) receptors. We were therefore motivated to investigate the effects of chronic oral R-baclofen administration in two independently generated mouse models of 16p11.2 microdeletion syndrome. In studies performed across two independent laboratories, we found that chronic activation of GABA(B) receptors improved performance on a series of cognitive and social tasks known to be impaired in two different 16p11.2 deletion mouse models. Our findings suggest that R-baclofen may have clinical utility for some of the core symptoms of human 16p11.2 microdeletion syndrome. Nature Publishing Group 2018-02 2017-11-15 /pmc/articles/PMC5770771/ /pubmed/28984295 http://dx.doi.org/10.1038/npp.2017.236 Text en Copyright © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/ |
spellingShingle | Original Article Stoppel, Laura J Kazdoba, Tatiana M Schaffler, Melanie D Preza, Anthony R Heynen, Arnold Crawley, Jacqueline N Bear, Mark F R-Baclofen Reverses Cognitive Deficits and Improves Social Interactions in Two Lines of 16p11.2 Deletion Mice |
title | R-Baclofen Reverses Cognitive Deficits and Improves Social Interactions in Two Lines of 16p11.2 Deletion Mice |
title_full | R-Baclofen Reverses Cognitive Deficits and Improves Social Interactions in Two Lines of 16p11.2 Deletion Mice |
title_fullStr | R-Baclofen Reverses Cognitive Deficits and Improves Social Interactions in Two Lines of 16p11.2 Deletion Mice |
title_full_unstemmed | R-Baclofen Reverses Cognitive Deficits and Improves Social Interactions in Two Lines of 16p11.2 Deletion Mice |
title_short | R-Baclofen Reverses Cognitive Deficits and Improves Social Interactions in Two Lines of 16p11.2 Deletion Mice |
title_sort | r-baclofen reverses cognitive deficits and improves social interactions in two lines of 16p11.2 deletion mice |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770771/ https://www.ncbi.nlm.nih.gov/pubmed/28984295 http://dx.doi.org/10.1038/npp.2017.236 |
work_keys_str_mv | AT stoppellauraj rbaclofenreversescognitivedeficitsandimprovessocialinteractionsintwolinesof16p112deletionmice AT kazdobatatianam rbaclofenreversescognitivedeficitsandimprovessocialinteractionsintwolinesof16p112deletionmice AT schafflermelanied rbaclofenreversescognitivedeficitsandimprovessocialinteractionsintwolinesof16p112deletionmice AT prezaanthonyr rbaclofenreversescognitivedeficitsandimprovessocialinteractionsintwolinesof16p112deletionmice AT heynenarnold rbaclofenreversescognitivedeficitsandimprovessocialinteractionsintwolinesof16p112deletionmice AT crawleyjacquelinen rbaclofenreversescognitivedeficitsandimprovessocialinteractionsintwolinesof16p112deletionmice AT bearmarkf rbaclofenreversescognitivedeficitsandimprovessocialinteractionsintwolinesof16p112deletionmice |