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Modulation of Tau Subcellular Localization as a Tool to Investigate the Expression of Disease-related Genes
Published on: December 20, 2019
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Presymptomatic change in microRNAs modulates Tau pathology
Salil Sharma1, Ines Khadimallah2, Adam Williamson Corya1
1Department of Psychological and Brain Sciences, the Linda and Jack Gill Center for Bimolecular Sciences, Indiana University, Bloomington, IN, 47405, USA.
Scientific Reports
|June 20, 2018
Summary
MicroRNA (miR) alterations in tauopathy brains contribute to neuroinflammation. Upregulated miR142 in tauopathy models increased glial cell activation, suggesting a role in disease pathology.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRs) are small non-coding RNAs regulating gene expression.
- Tauopathy is a neurodegenerative disease characterized by tau protein aggregation.
- Neuroinflammation is a key pathological feature in tauopathy.
Purpose of the Study:
- To investigate microRNA alterations in the hippocampus during tauopathy.
- To determine the role of specific microRNAs, like miR142, in tauopathy-associated neuroinflammation.
Main Methods:
- Utilized rTg4510 mice (Tau mice) as a tauopathy model.
- Performed miR-RNA pairing analysis with QIAGEN Ingenuity Pathway Analysis (IPA).
- Confirmed miR expression using real-time qPCR and transcriptome studies (RNAseq).
Main Results:
- Identified 71 altered miRs regulating 401 genes in presymptomatic Tau hippocampi.
- Found significant upregulation of miR142 (-3p and -5p) in Tau hippocampi from two weeks of age.
- Overexpression of miR142 in wildtype neurons increased glial markers (Gfap, Csf1) and cell numbers.
Conclusions:
- Tau overexpression leads to microRNA alterations in the brain.
- miR142 upregulation is implicated in tauopathy pathogenesis.
- MicroRNA changes contribute to neuroinflammation in tauopathy.
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