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Mol Brain. 2016 Jan 8;9:5. doi: 10.1186/s13041-016-0186-6.

PINK1 expression increases during brain development and stem cell differentiation, and affects the development of GFAP-positive astrocytes.

Choi I1,2, Choi DJ3, Yang H4, Woo JH5, Chang MY6, Kim JY7, Sun W8, Park SM9,10,11, Jou I12,13,14, Lee SH15, Joe EH16,17,18,19,20.

Author information

1
Neuroscience Graduate Program Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Korea. cnscis@gmail.com.
2
Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, Korea. cnscis@gmail.com.
3
Neuroscience Graduate Program Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Korea. djchoi81@ajou.ac.kr.
4
Department of Pharmacology, Ajou University School of Medicine san-5, Woncheon-dong, Youngtong-gu, Suwon, Kyunggi-do, 442-721, Korea. yanghaijie168@gmail.com.
5
Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, Korea. joohongwoo@daum.net.
6
Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Korea. mychang@hanyang.ac.kr.
7
Department of Anatomy and Division of Brain Korea 21 Plus Biomedical Science, Korea University College of Medicine, Seoul, 136-705, Korea. foxpporu@naver.com.
8
Department of Anatomy and Division of Brain Korea 21 Plus Biomedical Science, Korea University College of Medicine, Seoul, 136-705, Korea. woongsun@korea.ac.kr.
9
Neuroscience Graduate Program Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Korea. sangmyun@ajou.ac.kr.
10
Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, Korea. sangmyun@ajou.ac.kr.
11
Department of Pharmacology, Ajou University School of Medicine san-5, Woncheon-dong, Youngtong-gu, Suwon, Kyunggi-do, 442-721, Korea. sangmyun@ajou.ac.kr.
12
Neuroscience Graduate Program Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Korea. jouilo@ajou.ac.kr.
13
Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, Korea. jouilo@ajou.ac.kr.
14
Department of Pharmacology, Ajou University School of Medicine san-5, Woncheon-dong, Youngtong-gu, Suwon, Kyunggi-do, 442-721, Korea. jouilo@ajou.ac.kr.
15
Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Korea. leesh@hanyang.ac.kr.
16
Neuroscience Graduate Program Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Korea. ehjoe@ajou.ac.kr.
17
Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, Korea. ehjoe@ajou.ac.kr.
18
Department of Pharmacology, Ajou University School of Medicine san-5, Woncheon-dong, Youngtong-gu, Suwon, Kyunggi-do, 442-721, Korea. ehjoe@ajou.ac.kr.
19
Department of Brain Science, Ajou University School of Medicine, Suwon, Korea. ehjoe@ajou.ac.kr.
20
Brain Disease Research Center, Ajou University School of Medicine, Suwon, Korea. ehjoe@ajou.ac.kr.

Abstract

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.

PMID:
26746235
PMCID:
PMC4706723
DOI:
10.1186/s13041-016-0186-6
[Indexed for MEDLINE]
Free PMC Article

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