Exp Neurobiol.  2016 Feb;25(1):14-23. 10.5607/en.2016.25.1.14.

PINK1 Deficiency Decreases Expression Levels of mir-326, mir-330, and mir-3099 during Brain Development and Neural Stem Cell Differentiation

Affiliations
  • 1Neuroscience Graduate Program Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, Korea. ehjoe@ajou.ac.kr
  • 2Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 16499, Korea.
  • 3Department of Pharmacology, Ajou University School of Medicine, Suwon 16499, Korea.
  • 4Department of Brain Science, Ajou University School of Medicine, Suwon 16499, Korea.
  • 5Brain Disease Research Center, Ajou University School of Medicine, Suwon 16499, Korea.

Abstract

PTEN-induced putative kinase 1 (PINK1) is a Parkinson's disease (PD) gene. We examined miRNAs regulated by PINK1 during brain development and neural stem cell (NSC) differentiation, and found that lvels of miRNAs related to tumors and inflammation were different between 1-day-old-wild type (WT) and PINK1-knockout (KO) mouse brains. Notably, levels of miR-326, miR-330 and miR-3099, which are related to astroglioma, increased during brain development and NSC differentiation, and were significantly reduced in the absence of PINK1. Interestingly, in the presence of ciliary neurotrophic factor (CNTF), which pushes differentiation of NSCs into astrocytes, miR-326, miR-330, and miR-3099 levels in KO NSCs were also lower than those in WT NSCs. Furthermore, mimics of all three miRNAs increased expression of the astrocytic marker glial fibrillary acidic protein (GFAP) during differentiation of KO NSCs, but inhibitors of these miRNAs decreased GFAP expression in WT NSCs. Moreover, these miRNAs increased the translational efficacy of GFAP through the 3'-UTR of GFAP mRNA. Taken together, these results suggest that PINK1 deficiency reduce expression levels of miR-326, miR-330 and miR-3099, which may regulate GFAP expression during NSC differentiation and brain development.

Keyword

PINK1; Parkinson's disease; miR-326; miR-330; miR-3099

MeSH Terms

Animals
Astrocytes
Astrocytoma
Brain*
Ciliary Neurotrophic Factor
Glial Fibrillary Acidic Protein
Inflammation
Mice
MicroRNAs
Neural Stem Cells*
Parkinson Disease
Phosphotransferases
RNA, Messenger
Ciliary Neurotrophic Factor
Glial Fibrillary Acidic Protein
MicroRNAs
Phosphotransferases
RNA, Messenger
Full Text Links
  • EN
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2023 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr