Presymptomatic change in microRNAs modulates Tau pathology.

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State: Public
Version: Final published version
License: Not specified
Serval ID
serval:BIB_137E77F61E53
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Presymptomatic change in microRNAs modulates Tau pathology.
Journal
Scientific reports
Author(s)
Sharma S., Khadimallah I., Corya A.W., Ali Y.O., Rao X., Liu Y., Lu H.C.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
18/06/2018
Peer-reviewed
Oui
Volume
8
Number
1
Pages
9251
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
MicroRNAs (miRs) are 18~23 nucleotides long non-coding RNAs that regulate gene expression. To explore whether miR alterations in tauopathy contribute to pathological conditions, we first determined which hippocampal miRs are altered at the presymptomatic and symptomatic stages of tauopathy using rTg4510 mice (Tau mice), a well-characterized tauopathy model. miR-RNA pairing analysis using QIAGEN Ingenuity Pathway Analysis (IPA) revealed 401 genes that can be regulated by 71 miRs altered in Tau hippocampi at the presymptomatic stage. Among several miRs confirmed with real-time qPCR, miR142 (-3p and -5p) in Tau hippocampi were significantly upregulated by two-weeks of age and onward. Transcriptome studies by RNAseq and IPA revealed several overlapping biological and disease associated pathways affected by either Tau or miR142 overexpression, including Signal Transducer and Activator of Transcription 3 (Stat3) and Tumor Necrosis Factor Receptor 2 (Tnfr2) signaling pathways. Similar to what was observed in Tau brains, overexpressing miR142 in wildtype cortical neurons augments mRNA levels of Glial Fibrillary Acidic Protein (Gfap) and Colony Stimulating Factor 1 (Csf1), accompanied by a significant increase in microglia and reactive astrocyte numbers. Taken together, our study suggests that miR alterations by Tau overexpression may contribute to the neuroinflammation observed in Tau brains.
Keywords
Aging/genetics, Animals, Female, Gene Regulatory Networks, Hippocampus/metabolism, Humans, Mice, Inbred ICR, Mice, Transgenic, MicroRNAs/genetics, MicroRNAs/metabolism, Microglia/metabolism, Neurons/metabolism, RNA, Messenger/genetics, RNA, Messenger/metabolism, Tauopathies/genetics, Transcription, Genetic, Transcriptome/genetics, Up-Regulation/genetics, tau Proteins/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
12/07/2018 14:07
Last modification date
14/10/2019 6:09
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