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PINK1 expression increases during brain development and stem cell differentiation, and affects the development of GFAP-positive astrocytes
BACKGROUND: Mutation of PTEN-induced putative kinase 1 (PINK1) causes autosomal recessive early-onset Parkinson’s disease (PD). Despite of its ubiquitous expression in brain, its roles in non-neuronal cells such as neural stem cells (NSCs) and astrocytes were poorly unknown. RESULTS: We show that PI...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4706723/ https://www.ncbi.nlm.nih.gov/pubmed/26746235 http://dx.doi.org/10.1186/s13041-016-0186-6 |
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author | Choi, Insup Choi, Dong-Joo Yang, Haijie Woo, Joo Hong Chang, Mi-Yoon Kim, Joo Yeon Sun, Woong Park, Sang-Myun Jou, Ilo Lee, Sang Hoon Joe, Eun-Hye |
author_facet | Choi, Insup Choi, Dong-Joo Yang, Haijie Woo, Joo Hong Chang, Mi-Yoon Kim, Joo Yeon Sun, Woong Park, Sang-Myun Jou, Ilo Lee, Sang Hoon Joe, Eun-Hye |
author_sort | Choi, Insup |
collection | PubMed |
description | BACKGROUND: Mutation of PTEN-induced putative kinase 1 (PINK1) causes autosomal recessive early-onset Parkinson’s disease (PD). Despite of its ubiquitous expression in brain, its roles in non-neuronal cells such as neural stem cells (NSCs) and astrocytes were poorly unknown. RESULTS: We show that PINK1 expression increases from embryonic day 12 to postnatal day 1 in mice, which represents the main period of brain development. PINK1 expression also increases during neural stem cell (NSC) differentiation. Interestingly, expression of GFAP (a marker of astrocytes) was lower in PINK1 knockout (KO) mouse brain lysates compared to wild-type (WT) lysates at postnatal days 1-8, whereas there was little difference in the expression of markers for other brain cell types (e.g., neurons and oligodendrocytes). Further experiments showed that PINK1-KO NSCs were defective in their differentiation to astrocytes, producing fewer GFAP-positive cells compared to WT NSCs. However, the KO and WT NSCs did not differ in their self-renewal capabilities or ability to differentiate to neurons and oligodendrocytes. Interestingly, during differentiation of KO NSCs there were no defects in mitochondrial function, and there were not changes in signaling molecules such as SMAD1/5/8, STAT3, and HES1 involved in differentiation of NSCs into astrocytes. In brain sections, GFAP-positive astrocytes were more sparsely distributed in the corpus callosum and substantia nigra of KO animals compared with WT. CONCLUSION: Our study suggests that PINK1 deficiency causes defects in GFAP-positive astrogliogenesis during brain development and NSC differentiation, which may be a factor to increase risk for PD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13041-016-0186-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4706723 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-47067232016-01-10 PINK1 expression increases during brain development and stem cell differentiation, and affects the development of GFAP-positive astrocytes Choi, Insup Choi, Dong-Joo Yang, Haijie Woo, Joo Hong Chang, Mi-Yoon Kim, Joo Yeon Sun, Woong Park, Sang-Myun Jou, Ilo Lee, Sang Hoon Joe, Eun-Hye Mol Brain Research BACKGROUND: Mutation of PTEN-induced putative kinase 1 (PINK1) causes autosomal recessive early-onset Parkinson’s disease (PD). Despite of its ubiquitous expression in brain, its roles in non-neuronal cells such as neural stem cells (NSCs) and astrocytes were poorly unknown. RESULTS: We show that PINK1 expression increases from embryonic day 12 to postnatal day 1 in mice, which represents the main period of brain development. PINK1 expression also increases during neural stem cell (NSC) differentiation. Interestingly, expression of GFAP (a marker of astrocytes) was lower in PINK1 knockout (KO) mouse brain lysates compared to wild-type (WT) lysates at postnatal days 1-8, whereas there was little difference in the expression of markers for other brain cell types (e.g., neurons and oligodendrocytes). Further experiments showed that PINK1-KO NSCs were defective in their differentiation to astrocytes, producing fewer GFAP-positive cells compared to WT NSCs. However, the KO and WT NSCs did not differ in their self-renewal capabilities or ability to differentiate to neurons and oligodendrocytes. Interestingly, during differentiation of KO NSCs there were no defects in mitochondrial function, and there were not changes in signaling molecules such as SMAD1/5/8, STAT3, and HES1 involved in differentiation of NSCs into astrocytes. In brain sections, GFAP-positive astrocytes were more sparsely distributed in the corpus callosum and substantia nigra of KO animals compared with WT. CONCLUSION: Our study suggests that PINK1 deficiency causes defects in GFAP-positive astrogliogenesis during brain development and NSC differentiation, which may be a factor to increase risk for PD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13041-016-0186-6) contains supplementary material, which is available to authorized users. BioMed Central 2016-01-08 /pmc/articles/PMC4706723/ /pubmed/26746235 http://dx.doi.org/10.1186/s13041-016-0186-6 Text en © Choi et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Choi, Insup Choi, Dong-Joo Yang, Haijie Woo, Joo Hong Chang, Mi-Yoon Kim, Joo Yeon Sun, Woong Park, Sang-Myun Jou, Ilo Lee, Sang Hoon Joe, Eun-Hye PINK1 expression increases during brain development and stem cell differentiation, and affects the development of GFAP-positive astrocytes |
title | PINK1 expression increases during brain development and stem cell differentiation, and affects the development of GFAP-positive astrocytes |
title_full | PINK1 expression increases during brain development and stem cell differentiation, and affects the development of GFAP-positive astrocytes |
title_fullStr | PINK1 expression increases during brain development and stem cell differentiation, and affects the development of GFAP-positive astrocytes |
title_full_unstemmed | PINK1 expression increases during brain development and stem cell differentiation, and affects the development of GFAP-positive astrocytes |
title_short | PINK1 expression increases during brain development and stem cell differentiation, and affects the development of GFAP-positive astrocytes |
title_sort | pink1 expression increases during brain development and stem cell differentiation, and affects the development of gfap-positive astrocytes |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4706723/ https://www.ncbi.nlm.nih.gov/pubmed/26746235 http://dx.doi.org/10.1186/s13041-016-0186-6 |
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