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Brain Res. 2018 Jan 1;1678:374-383. doi: 10.1016/j.brainres.2017.11.009. Epub 2017 Nov 13.

MicroRNA expression patterns in human anterior cingulate and motor cortex: A study of dementia with Lewy bodies cases and controls.

Author information

1
Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA; Department of Pathology, University of Kentucky, Lexington, KY 40536, USA. Electronic address: pnels2@email.uky.edu.
2
Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA.
3
Department of Statistics, University of Kentucky, Lexington, KY 40536, USA.
4
Department of Statistics, University of Kentucky, Lexington, KY 40536, USA. Electronic address: katherine.thompson@uky.edu.

Abstract

OVERVIEW:

MicroRNAs (miRNAs) have been implicated in neurodegenerative diseases including Parkinson's disease and Alzheimer's disease (AD). Here, we evaluated the expression of miRNAs in anterior cingulate (AC; Brodmann area [BA] 24) and primary motor (MO; BA 4) cortical tissue from aged human brains in the University of Kentucky AD Center autopsy cohort, with a focus on dementia with Lewy bodies (DLB).

METHODS:

RNA was isolated from gray matter of brain samples with pathology-defined DLB, AD, AD + DLB, and low-pathology controls, with n = 52 cases initially included (n  = 23 with DLB), all with low (<4 h) postmortem intervals. RNA was profiled using Exiqon miRNA microarrays. Quantitative PCR for post hoc replication was performed on separate cases (n = 6 controls) and included RNA isolated from gray matter of MO, AC, primary somatosensory (BA 3), and dorsolateral prefrontal (BA 9) cortical regions.

RESULTS:

The miRNA expression patterns differed substantially according to anatomic location: of the relatively highly-expressed miRNAs, 150/481 (31%) showed expression that was different between AC versus MO (at p < .05 following correction for multiple comparisons), most (79%) with higher expression in MO. A subset of these results were confirmed in qPCR validation focusing on miR-7, miR-153, miR-133b, miR-137, and miR-34a. No significant variation in miRNA expression was detected in association with either neuropathology or sex after correction for multiple comparisons.

CONCLUSION:

A subset of miRNAs (some previously associated with α-synucleinopathy and/or directly targeting α-synuclein mRNA) were differentially expressed in AC and MO, which may help explain why these brain regions show differences in vulnerability to Lewy body pathology.

KEYWORDS:

Brain; Epigenetic; Frontal; Gender; Neuroanatomy; Neuropathology; Noncoding; Sensory; Synuclein; miR-107; miR-133; miR-15; miR-15/107; miR-16

PMID:
29146111
PMCID:
PMC5752138
[Available on 2019-01-01]
DOI:
10.1016/j.brainres.2017.11.009
[Indexed for MEDLINE]

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