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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
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.
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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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