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

• Choi I
• Woo JH
• Jou I
• Joe EH

• KMID: 2165574
• DOI: http://doi.org/10.5607/en.2016.25.1.14

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