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Published on: July 19, 2019
Microarray RNA expression analysis of cerebral white matter lesions reveals changes in multiple functional pathways.
Julie E Simpson1, Ola Hosny, Stephen B Wharton
1Academic Units of Pathology, University of Sheffield, Sheffield, UK.
Stroke
|December 26, 2008
Summary
White matter lesions (WML) in aging brains involve complex molecular changes beyond ischemia, impacting immune regulation and cell processes. Surrounding white matter also shows altered gene expression, suggesting a field effect.
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- White matter lesions (WML) are associated with cognitive decline and depression in aging brains.
- Ischemia is a known contributor to WML pathogenesis, but other mechanisms are likely involved.
Purpose of the Study:
- To investigate additional pathogenetic mechanisms of WML using an unbiased RNA microarray analysis.
- To identify altered gene expression pathways in WML compared to normal white matter.
Main Methods:
- WML were identified via MRI and pathology in donated brains.
- RNA microarray analysis compared WML with nonlesional white matter (WM[L] and WM[C]).
- Functional pathways were validated using quantitative real-time PCR and immunocytochemistry.
Main Results:
- 502 genes showed differential expression in WML compared to WM[C], involving 8 major pathways (e.g., immune regulation, apoptosis, metabolism).
- 409 genes were altered in WM[L], implicating similar pathways.
- Validation confirmed expected changes in RNA and protein expression for selected genes.
Conclusions:
- WML exhibit a complex molecular phenotype potentially involving factors beyond ischemia, such as blood-brain barrier dysfunction.
- Altered gene expression in WM[L] suggests a "field effect" in the white matter surrounding lesions.
