Presymptomatic change in microRNAs modulates Tau pathology

dc.contributor.authorSharma, Salil
dc.contributor.authorKhadimallah, Ines
dc.contributor.authorCorya, Adam Williamson
dc.contributor.authorAli, Yousuf Omar
dc.contributor.authorRao, Xi
dc.contributor.authorLiu, Yunlong
dc.contributor.authorLu, Hui-Chen
dc.contributor.departmentMedical and Molecular Genetics, School of Medicineen_US
dc.date.accessioned2019-01-17T16:22:11Z
dc.date.available2019-01-17T16:22:11Z
dc.date.issued2018-06-18
dc.description.abstractMicroRNAs (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.en_US
dc.eprint.versionFinal published versionen_US
dc.identifier.citationSharma, S., Khadimallah, I., Corya, A. W., Ali, Y. O., Rao, X., Liu, Y., & Lu, H. C. (2018). Presymptomatic change in microRNAs modulates Tau pathology. Scientific reports, 8(1), 9251. doi:10.1038/s41598-018-27527-6en_US
dc.identifier.urihttps://hdl.handle.net/1805/18184
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionof10.1038/s41598-018-27527-6en_US
dc.relation.journalScientific reportsen_US
dc.rightsAttribution 3.0 United States
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/us
dc.sourcePMCen_US
dc.subjectPresymptomatic changeen_US
dc.subjectmicroRNAsen_US
dc.subjectTau pathologyen_US
dc.subjectGlial Fibrillary Acidic Proteinen_US
dc.subjectColony Stimulating Factor 1en_US
dc.subjectMicrogliaen_US
dc.subjectNeuroinflammationen_US
dc.subjectSignal Transduceren_US
dc.subjectActivator of Transcription 3en_US
dc.subjectTumor Necrosis Factor Receptor 2en_US
dc.titlePresymptomatic change in microRNAs modulates Tau pathologyen_US
dc.typeArticleen_US
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