Abstract
The present study analyzes by RT-qPCR the expression of microRNA (miRNA)-27a-3p, miRNA-124-3p, miRNA-132-3p, and miRNA-143-3p in the locus coeruleus (LC), entorhinal cortex (EC), CA1 region of the hippocampus (CA1), and dentate gyrus (DG) of middle-aged (MA) individuals with no brain lesions and of cases at Braak and Braak stages I-II and II-IV of neurofibrillary tangle (NFT) pathology. The most affected region is the LC in which miRNA-27a-3p, miRNA-124-3p, and miRNA-143-3p show a trend to increase at stages I-II and are significantly up-regulated at stages III-IV when compared with MA. Only miRNA-143-3p is up-regulated in the EC at stages III-IV when compared with MA and with stages I-II. No modifications in the expression levels of miRNA-27a-3p, miRNA-124-3p, miRNA-132-3p, and miRNA-143-3p are found in CA1 at any stage, whereas miRNA-124-3p is significantly down-regulated in DG at stages I-II. Accompanying in situ hybridization reveals miRNA-27a-3p, miRNA-124-3p, and miRNA-143-3 localization in neurons, indicating that changes in miRNA expression are not a direct effect of changes in the numbers of neurons and glial cells. Present observations show for the first time important miRNA de-regulation in the LC at the first stages of NFT. Since the LC is the main noradrenergic input to the cerebral cortex, key regulator of mood and depression, and one of the first nuclei affected in aging and Alzheimer’s disease (AD), these findings provide insights for additional study of the LC in aging and AD.
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Acknowledgements
This study was supported by grants from CIBERNED and Instituto de Salud Carlos III (Ministerio de Economía y Competitividad) co-funded by FEDER funds/European Regional Development Fund (ERDF)—a way to build Europe: PIE14/00034 and PI14/00757 to IF, by the Spanish Ministry of Health—Instituto Carlos III (Miguel Servet - CP16/00041) to FL and IFI15/00035 fellowship to PA-B; and by the Alzheimer-Forschungs-Initiative e.V. (AFI 12851) to IZ. We thank T. Yohannan for editorial help.
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FL, KT, and WT carried out RT-qPCR and in situ hybridization; PA and BA performed RT-qPCR; KHO contributed to the selection of samples and dissection of tissues; FL, IZ, and EM designed the microRNA study; and IF designed the study, supervised all the results, and wrote the manuscript which was circulated among the authors. All the authors contributed to the final discussion and approval of the manuscript.
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Human brain tissue was obtained from the Institute of Neuropathology Brain Bank (HUB-ICO-IDIBELL Biobank, Barcelona, Spain) following the guidelines of Spanish legislation and the approval of the local ethics committee.
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The authors declare that they have no competing interests.
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Llorens, F., Thüne, K., Andrés-Benito, P. et al. MicroRNA Expression in the Locus Coeruleus, Entorhinal Cortex, and Hippocampus at Early and Middle Stages of Braak Neurofibrillary Tangle Pathology. J Mol Neurosci 63, 206–215 (2017). https://doi.org/10.1007/s12031-017-0971-4
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DOI: https://doi.org/10.1007/s12031-017-0971-4