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Chronic bryostatin-1 rescues autistic and cognitive phenotypes in the fragile X mice
Fragile X syndrome (FXS), an X-chromosome linked intellectual disability, is the leading monogenetic cause of autism spectrum disorder (ASD), a neurodevelopmental condition that currently has no specific drug treatment. Building upon the demonstrated therapeutic effects on spatial memory of bryostat...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581799/ https://www.ncbi.nlm.nih.gov/pubmed/33093534 http://dx.doi.org/10.1038/s41598-020-74848-6 |
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author | Cogram, Patricia Alkon, Daniel L. Crockford, David Deacon, Robert M. J. Hurley, Michael J. Altimiras, Francisco Sun, Miao-Kun Tranfaglia, Michael |
author_facet | Cogram, Patricia Alkon, Daniel L. Crockford, David Deacon, Robert M. J. Hurley, Michael J. Altimiras, Francisco Sun, Miao-Kun Tranfaglia, Michael |
author_sort | Cogram, Patricia |
collection | PubMed |
description | Fragile X syndrome (FXS), an X-chromosome linked intellectual disability, is the leading monogenetic cause of autism spectrum disorder (ASD), a neurodevelopmental condition that currently has no specific drug treatment. Building upon the demonstrated therapeutic effects on spatial memory of bryostatin-1, a relatively specific activator of protein kinase C (PKC)ε, (also of PKCα) on impaired synaptic plasticity/maturation and spatial learning and memory in FXS mice, we investigated whether bryostatin-1 might affect the autistic phenotypes and other behaviors, including open field activity, activities of daily living (nesting and marble burying), at the effective therapeutic dose for spatial memory deficits. Further evaluation included other non-spatial learning and memory tasks. Interestingly, a short period of treatment (5 weeks) only produced very limited or no therapeutic effects on the autistic and cognitive phenotypes in the Fmr1 KO2 mice, while a longer treatment (13 weeks) with the same dose of bryostatin-1 effectively rescued the autistic and non-spatial learning deficit cognitive phenotypes. It is possible that longer-term treatment would result in further improvement in these fragile X phenotypes. This effect is clearly different from other treatment strategies tested to date, in that the drug shows little acute effect, but strong long-term effects. It also shows no evidence of tolerance, which has been a problem with other drug classes (mGluR5 antagonists, GABA-A and -B agonists). The results strongly suggest that, at appropriate dosing and therapeutic period, chronic bryostatin-1 may have great therapeutic value for both ASD and FXS. |
format | Online Article Text |
id | pubmed-7581799 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75817992020-10-23 Chronic bryostatin-1 rescues autistic and cognitive phenotypes in the fragile X mice Cogram, Patricia Alkon, Daniel L. Crockford, David Deacon, Robert M. J. Hurley, Michael J. Altimiras, Francisco Sun, Miao-Kun Tranfaglia, Michael Sci Rep Article Fragile X syndrome (FXS), an X-chromosome linked intellectual disability, is the leading monogenetic cause of autism spectrum disorder (ASD), a neurodevelopmental condition that currently has no specific drug treatment. Building upon the demonstrated therapeutic effects on spatial memory of bryostatin-1, a relatively specific activator of protein kinase C (PKC)ε, (also of PKCα) on impaired synaptic plasticity/maturation and spatial learning and memory in FXS mice, we investigated whether bryostatin-1 might affect the autistic phenotypes and other behaviors, including open field activity, activities of daily living (nesting and marble burying), at the effective therapeutic dose for spatial memory deficits. Further evaluation included other non-spatial learning and memory tasks. Interestingly, a short period of treatment (5 weeks) only produced very limited or no therapeutic effects on the autistic and cognitive phenotypes in the Fmr1 KO2 mice, while a longer treatment (13 weeks) with the same dose of bryostatin-1 effectively rescued the autistic and non-spatial learning deficit cognitive phenotypes. It is possible that longer-term treatment would result in further improvement in these fragile X phenotypes. This effect is clearly different from other treatment strategies tested to date, in that the drug shows little acute effect, but strong long-term effects. It also shows no evidence of tolerance, which has been a problem with other drug classes (mGluR5 antagonists, GABA-A and -B agonists). The results strongly suggest that, at appropriate dosing and therapeutic period, chronic bryostatin-1 may have great therapeutic value for both ASD and FXS. Nature Publishing Group UK 2020-10-22 /pmc/articles/PMC7581799/ /pubmed/33093534 http://dx.doi.org/10.1038/s41598-020-74848-6 Text en © The Author(s) 2020 Open Access This 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/. |
spellingShingle | Article Cogram, Patricia Alkon, Daniel L. Crockford, David Deacon, Robert M. J. Hurley, Michael J. Altimiras, Francisco Sun, Miao-Kun Tranfaglia, Michael Chronic bryostatin-1 rescues autistic and cognitive phenotypes in the fragile X mice |
title | Chronic bryostatin-1 rescues autistic and cognitive phenotypes in the fragile X mice |
title_full | Chronic bryostatin-1 rescues autistic and cognitive phenotypes in the fragile X mice |
title_fullStr | Chronic bryostatin-1 rescues autistic and cognitive phenotypes in the fragile X mice |
title_full_unstemmed | Chronic bryostatin-1 rescues autistic and cognitive phenotypes in the fragile X mice |
title_short | Chronic bryostatin-1 rescues autistic and cognitive phenotypes in the fragile X mice |
title_sort | chronic bryostatin-1 rescues autistic and cognitive phenotypes in the fragile x mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581799/ https://www.ncbi.nlm.nih.gov/pubmed/33093534 http://dx.doi.org/10.1038/s41598-020-74848-6 |
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