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Cerebellar Predominant Increase in mRNA Expression Levels of Sirt1 and Sirt3 Isoforms in a Transgenic Mouse Model of Huntington’s Disease
The potential role of Sirt1 and Sirt2 subtypes of Sirtuins (class III NAD(+)-dependent deacetylases) in the pathogenesis of Huntington’s disease (HD) has been extensively studied yielding some controversial results. However, data regarding the involvement of Sirt3 and their variants in HD are consid...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423862/ https://www.ncbi.nlm.nih.gov/pubmed/32524313 http://dx.doi.org/10.1007/s11064-020-03069-0 |
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author | Salamon, Andras Maszlag-Török, Rita Veres, Gábor Boros, Fanni Annamária Vágvölgyi-Sümegi, Evelin Somogyi, Anett Vécsei, László Klivényi, Péter Zádori, Dénes |
author_facet | Salamon, Andras Maszlag-Török, Rita Veres, Gábor Boros, Fanni Annamária Vágvölgyi-Sümegi, Evelin Somogyi, Anett Vécsei, László Klivényi, Péter Zádori, Dénes |
author_sort | Salamon, Andras |
collection | PubMed |
description | The potential role of Sirt1 and Sirt2 subtypes of Sirtuins (class III NAD(+)-dependent deacetylases) in the pathogenesis of Huntington’s disease (HD) has been extensively studied yielding some controversial results. However, data regarding the involvement of Sirt3 and their variants in HD are considerably limited. The aim of this study was to assess the expression pattern of Sirt1 and three Sirt3 mRNA isoforms (Sirt3-M1/2/3) in the striatum, cortex and cerebellum in respect of the effect of gender, age and the presence of the transgene using the N171-82Q transgenic mouse model of HD. Striatal, cortical and cerebellar Sirt1-Fl and Sirt3-M1/2/3 mRNA levels were measured in 8, 12 and 16 weeks old N171-82Q transgenic mice and in their wild-type littermates. Regarding the striatum and cortex, the presence of the transgene resulted in a significant increase in Sirt3-M3 and Sirt1 mRNA levels, respectively, whereas in case of the cerebellum the transgene resulted in increased expression of all the assessed subtypes and isoforms. Aging exerted minor influence on Sirt mRNA expression levels, both in transgene carriers and in their wild-type littermates, and there was no interaction between the presence of the transgene and aging. Furthermore, there was no difference between genders. The unequivocal cerebellar Sirtuin activation with presumed compensatory role suggests that the cerebellum might be another key player in HD in addition to the most severely affected striatum. The mitochondrially acting Sirt3 may serve as an interesting novel therapeutic target in this deleterious condition. |
format | Online Article Text |
id | pubmed-7423862 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-74238622020-08-18 Cerebellar Predominant Increase in mRNA Expression Levels of Sirt1 and Sirt3 Isoforms in a Transgenic Mouse Model of Huntington’s Disease Salamon, Andras Maszlag-Török, Rita Veres, Gábor Boros, Fanni Annamária Vágvölgyi-Sümegi, Evelin Somogyi, Anett Vécsei, László Klivényi, Péter Zádori, Dénes Neurochem Res Original Paper The potential role of Sirt1 and Sirt2 subtypes of Sirtuins (class III NAD(+)-dependent deacetylases) in the pathogenesis of Huntington’s disease (HD) has been extensively studied yielding some controversial results. However, data regarding the involvement of Sirt3 and their variants in HD are considerably limited. The aim of this study was to assess the expression pattern of Sirt1 and three Sirt3 mRNA isoforms (Sirt3-M1/2/3) in the striatum, cortex and cerebellum in respect of the effect of gender, age and the presence of the transgene using the N171-82Q transgenic mouse model of HD. Striatal, cortical and cerebellar Sirt1-Fl and Sirt3-M1/2/3 mRNA levels were measured in 8, 12 and 16 weeks old N171-82Q transgenic mice and in their wild-type littermates. Regarding the striatum and cortex, the presence of the transgene resulted in a significant increase in Sirt3-M3 and Sirt1 mRNA levels, respectively, whereas in case of the cerebellum the transgene resulted in increased expression of all the assessed subtypes and isoforms. Aging exerted minor influence on Sirt mRNA expression levels, both in transgene carriers and in their wild-type littermates, and there was no interaction between the presence of the transgene and aging. Furthermore, there was no difference between genders. The unequivocal cerebellar Sirtuin activation with presumed compensatory role suggests that the cerebellum might be another key player in HD in addition to the most severely affected striatum. The mitochondrially acting Sirt3 may serve as an interesting novel therapeutic target in this deleterious condition. Springer US 2020-06-10 2020 /pmc/articles/PMC7423862/ /pubmed/32524313 http://dx.doi.org/10.1007/s11064-020-03069-0 Text en © The Author(s) 2020 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/. |
spellingShingle | Original Paper Salamon, Andras Maszlag-Török, Rita Veres, Gábor Boros, Fanni Annamária Vágvölgyi-Sümegi, Evelin Somogyi, Anett Vécsei, László Klivényi, Péter Zádori, Dénes Cerebellar Predominant Increase in mRNA Expression Levels of Sirt1 and Sirt3 Isoforms in a Transgenic Mouse Model of Huntington’s Disease |
title |
Cerebellar Predominant Increase in mRNA Expression Levels of Sirt1 and Sirt3 Isoforms in a Transgenic Mouse Model of Huntington’s Disease |
title_full |
Cerebellar Predominant Increase in mRNA Expression Levels of Sirt1 and Sirt3 Isoforms in a Transgenic Mouse Model of Huntington’s Disease |
title_fullStr |
Cerebellar Predominant Increase in mRNA Expression Levels of Sirt1 and Sirt3 Isoforms in a Transgenic Mouse Model of Huntington’s Disease |
title_full_unstemmed |
Cerebellar Predominant Increase in mRNA Expression Levels of Sirt1 and Sirt3 Isoforms in a Transgenic Mouse Model of Huntington’s Disease |
title_short |
Cerebellar Predominant Increase in mRNA Expression Levels of Sirt1 and Sirt3 Isoforms in a Transgenic Mouse Model of Huntington’s Disease |
title_sort | cerebellar predominant increase in mrna expression levels of sirt1 and sirt3 isoforms in a transgenic mouse model of huntington’s disease |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423862/ https://www.ncbi.nlm.nih.gov/pubmed/32524313 http://dx.doi.org/10.1007/s11064-020-03069-0 |
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