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PINK1 expression increases and regulates development of GFAP(+) astrocytes during brain development and stem cell differentiation

Choi, Insup; Choi, Dong-joo; Jou, Ilo; Joe, Eun-Hye
Department of Pharmacology, Ajou University School of Medicine; Chronic Inflammatory Disease Research Center, Ajou Research Institute for Innovative Medicine; Brain Disease Research Center, Ajou Research Institute for Innovative Medicine
PTEN-induced putative kinase 1 (PINK1) is a Parkinson's disease gene. In this study, we found that PINK1 expression increase during development of the brain and differentiation of neural stem cells (NSCs). Expression of GFAP, a marker of astrocytes, was lower in PINK1 KO brain than in wild type (WT) brain at postnatal day 1-8. GFAP-positive astrocytes were sparsely located in the substantia nigra (SN) and subventricular zones (SVZ) in KO brain compared with WT brain. Density of dopaminergic neurites in the SN was lower and/or less well organized in 8 d and/or 8 week old PINK1 KO mice. In the SVZ, expression of nestin, a marker of neural stem cells, also decreased in KO mice. Furthermore, PINK1 KO NSCs showed defects in differentiation into astrocytes: less number of GFAP-positive cells was produced from PINK1 KO NSCs compared with that from WT NSCs. However, neither self-renewal capabilities nor differentiation into neurons and oligodendrocytes were different in KO and WT NSCs. These results implicate that PINK1 deficiency causes defects in astrogliogenesis during brain development and neural stem cell differentiation, which may cause insufficient support of neurons and be a risk of the development of PD.
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