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MicroRNA expression patterns in human anterior cingulate and motor cortex: A study of dementia with Lewy bodies cases
Peter T Nelson1, Wang-Xia Wang2, Sarah A Janse3
1Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA; Department of Pathology, University of Kentucky, Lexington, KY 40536, USA.
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.
Insights
MicroRNA (miRNA) expression varies between brain regions, potentially explaining differing vulnerability in neurodegenerative diseases like dementia with Lewy bodies. This study analyzed miRNA patterns in anterior cingulate and motor cortex tissues.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- MicroRNAs (miRNAs) are increasingly recognized for their role in neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease.
- This study investigates miRNA expression in specific human brain regions, focusing on dementia with Lewy bodies (DLB).
Purpose of the Study:
- To evaluate and compare miRNA expression profiles in the anterior cingulate (AC) and primary motor (MO) cortical tissues of aged human brains.
- To identify potential correlations between miRNA expression patterns and regional vulnerability in neurodegenerative conditions, particularly DLB.
Main Methods:
- RNA was extracted from gray matter of brain samples from individuals with DLB, AD, mixed AD+DLB, and controls.
- MicroRNA expression was profiled using Exiqon miRNA microarrays, with subsequent validation via quantitative PCR (qPCR) on specific miRNAs (miR-7, miR-153, miR-133b, miR-137, miR-34a).
- Analysis included brain samples from AC, MO, primary somatosensory (BA 3), and dorsolateral prefrontal (BA 9) cortical regions.
Main Results:
- Significant differences in miRNA expression patterns were observed between the AC and MO cortical regions.
- Of the highly expressed miRNAs, 31% showed differential expression between AC and MO, with the majority (79%) being more abundant in the MO cortex.
- qPCR validation confirmed differential expression for a subset of miRNAs, including miR-7, miR-153, miR-133b, miR-137, and miR-34a.
- No significant variations in miRNA expression were associated with neuropathology or sex after correcting for multiple comparisons.
Conclusions:
- A subset of microRNAs exhibit differential expression in the anterior cingulate and motor cortex.
- These differentially expressed miRNAs, some linked to alpha-synucleinopathy or directly targeting alpha-synuclein mRNA, may contribute to the distinct vulnerability of these brain regions to Lewy body pathology.
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