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14-3-3γ haploinsufficiency leads to altered dopamine pathway and Parkinson’s disease-like motor incoordination in mice
The 14-3-3 protein family with seven isoforms found in mammals is widely expressed in the brain and plays various roles in cellular processes. Several studies have reported that 14-3-3γ, one of the 14-3-3 protein isoforms, is associated with neurological and psychiatric disorders, but the role of 14...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9817279/ https://www.ncbi.nlm.nih.gov/pubmed/36604743 http://dx.doi.org/10.1186/s13041-022-00990-z |
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author | Cho, Eunsil Park, Jinsil Hwang, Eun Mi Kim, Hyung Wook Park, Jae-Yong |
author_facet | Cho, Eunsil Park, Jinsil Hwang, Eun Mi Kim, Hyung Wook Park, Jae-Yong |
author_sort | Cho, Eunsil |
collection | PubMed |
description | The 14-3-3 protein family with seven isoforms found in mammals is widely expressed in the brain and plays various roles in cellular processes. Several studies have reported that 14-3-3γ, one of the 14-3-3 protein isoforms, is associated with neurological and psychiatric disorders, but the role of 14-3-3γ in the pathophysiology of brain diseases is unclear. Although studies have been conducted on the relationship between 14-3-3γ protein and Parkinson’s disease (PD), a common neurodegenerative disorder with severe motor symptoms such as bradykinesia and rigidity, a direct connection remains to be elucidated. We recently showed that adult heterozygous 14-3-3γ knockout mice are hyperactive and exhibit anxiety-like behavior. In this study, we further characterized the molecular and behavioral changes in aged 14-3-3γ heterozygous mice to investigate the role of 14-3-3γ in the brain. We observed decreased dopamine levels and altered dopamine metabolism in the brains of these mice, including changes in the phosphorylation of proteins implicated in PD pathology. Furthermore, we confirmed that they displayed PD symptom-like behavioral deficits, such as impaired motor coordination and decreased ability to the nest-building activity. These findings suggest an association between 14-3-3γ dysfunction and PD pathophysiology. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13041-022-00990-z. |
format | Online Article Text |
id | pubmed-9817279 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-98172792023-01-07 14-3-3γ haploinsufficiency leads to altered dopamine pathway and Parkinson’s disease-like motor incoordination in mice Cho, Eunsil Park, Jinsil Hwang, Eun Mi Kim, Hyung Wook Park, Jae-Yong Mol Brain Research The 14-3-3 protein family with seven isoforms found in mammals is widely expressed in the brain and plays various roles in cellular processes. Several studies have reported that 14-3-3γ, one of the 14-3-3 protein isoforms, is associated with neurological and psychiatric disorders, but the role of 14-3-3γ in the pathophysiology of brain diseases is unclear. Although studies have been conducted on the relationship between 14-3-3γ protein and Parkinson’s disease (PD), a common neurodegenerative disorder with severe motor symptoms such as bradykinesia and rigidity, a direct connection remains to be elucidated. We recently showed that adult heterozygous 14-3-3γ knockout mice are hyperactive and exhibit anxiety-like behavior. In this study, we further characterized the molecular and behavioral changes in aged 14-3-3γ heterozygous mice to investigate the role of 14-3-3γ in the brain. We observed decreased dopamine levels and altered dopamine metabolism in the brains of these mice, including changes in the phosphorylation of proteins implicated in PD pathology. Furthermore, we confirmed that they displayed PD symptom-like behavioral deficits, such as impaired motor coordination and decreased ability to the nest-building activity. These findings suggest an association between 14-3-3γ dysfunction and PD pathophysiology. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13041-022-00990-z. BioMed Central 2023-01-05 /pmc/articles/PMC9817279/ /pubmed/36604743 http://dx.doi.org/10.1186/s13041-022-00990-z Text en © The Author(s) 2023 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 Cho, Eunsil Park, Jinsil Hwang, Eun Mi Kim, Hyung Wook Park, Jae-Yong 14-3-3γ haploinsufficiency leads to altered dopamine pathway and Parkinson’s disease-like motor incoordination in mice |
title | 14-3-3γ haploinsufficiency leads to altered dopamine pathway and Parkinson’s disease-like motor incoordination in mice |
title_full | 14-3-3γ haploinsufficiency leads to altered dopamine pathway and Parkinson’s disease-like motor incoordination in mice |
title_fullStr | 14-3-3γ haploinsufficiency leads to altered dopamine pathway and Parkinson’s disease-like motor incoordination in mice |
title_full_unstemmed | 14-3-3γ haploinsufficiency leads to altered dopamine pathway and Parkinson’s disease-like motor incoordination in mice |
title_short | 14-3-3γ haploinsufficiency leads to altered dopamine pathway and Parkinson’s disease-like motor incoordination in mice |
title_sort | 14-3-3γ haploinsufficiency leads to altered dopamine pathway and parkinson’s disease-like motor incoordination in mice |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9817279/ https://www.ncbi.nlm.nih.gov/pubmed/36604743 http://dx.doi.org/10.1186/s13041-022-00990-z |
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