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J Mol Neurosci. 2017 Oct;63(2):206-215. doi: 10.1007/s12031-017-0971-4. Epub 2017 Sep 5.

MicroRNA Expression in the Locus Coeruleus, Entorhinal Cortex, and Hippocampus at Early and Middle Stages of Braak Neurofibrillary Tangle Pathology.

Author information

1
CIBERNED (Network Centre for Biomedical Research of Neurodegenerative Diseases), Institute Carlos III, Ministry of Health, Madrid, Spain.
2
Department of Neurology, University Medical School, Göttingen, Germany.
3
German Centre for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
4
Institute of Neuropathology, IDIBELL-University Hospital Bellvitge, Hospitalet de Llobregat, Spain.
5
Centre for Genomic Regulation, Barcelona, Spain.
6
CIBERNED (Network Centre for Biomedical Research of Neurodegenerative Diseases), Institute Carlos III, Ministry of Health, Madrid, Spain. 8082ifa@gmail.com.
7
Institute of Neuropathology, IDIBELL-University Hospital Bellvitge, Hospitalet de Llobregat, Spain. 8082ifa@gmail.com.
8
Department of Pathology and Experimental Therapeutics, Faculty of Medicine, University of Barcelona, c/Feixa Llarga sn, 08907, Hospitalet de Llobregat, Spain. 8082ifa@gmail.com.
9
Institute of Neurosciences, University of Barcelona, Barcelona, Spain. 8082ifa@gmail.com.

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.

KEYWORDS:

Alzheimer disease; Entorhinal cortex; Hippocampus; Locus coeruleus; MicroRNA; Neurofibrillary tangle pathology

PMID:
28871468
DOI:
10.1007/s12031-017-0971-4
[Indexed for MEDLINE]

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