Julie E. Simpson
Microarray RNA expression analysis of cerebral white matter lesions reveals changes in multiple functional pathways
Simpson, Julie E.; Hosny, Ola; Wharton, Stephen B.; Heath, Paul R.; Holden, Hazel; Fernando, Malee S.; Matthews, Fiona; Forster, Gill; O'Brien, John T.; Barber, Robert; Kalaria, Raj N.; Brayne, Carol; Shaw, Pamela J.; Lewis, Claire E.; Ince, Paul G.
Authors
Ola Hosny
Stephen B. Wharton
Paul R. Heath
Hazel Holden
Malee S. Fernando
Professor Fiona Matthews F.Matthews@hull.ac.uk
Pro-Vice-Chancellor Research and Enterprise
Gill Forster
John T. O'Brien
Robert Barber
Raj N. Kalaria
Carol Brayne
Pamela J. Shaw
Claire E. Lewis
Paul G. Ince
Abstract
Background and Purpose-White matter lesions (WML) in brain aging are linked to dementia and depression. Ischemia contributes to their pathogenesis but other mechanisms may contribute. We used RNA microarray analysis with functional pathway grouping as an unbiased approach to investigate evidence for additional pathogenetic mechanisms. Methods-WML were identified by MRI and pathology in brains donated to the Medical Research Council Cognitive Function and Ageing Study Cognitive Function and Aging Study. RNA was extracted to compare WML with nonlesional white matter samples from cases with lesions (WM[L]), and from cases with no lesions (WM[C]) using RNA microarray and pathway analysis. Functional pathways were validated for selected genes by quantitative real-time polymerase chain reaction and immunocytochemistry. Results-We identified 8 major pathways in which multiple genes showed altered RNA transcription (immune regulation, cell cycle, apoptosis, proteolysis, ion transport, cell structure, electron transport, metabolism) among 502 genes that were differentially expressed in WML compared to WM[C]. In WM[L], 409 genes were altered involving the same pathways. Genes selected to validate this microarray data all showed the expected changes in RNA levels and immunohistochemical expression of protein. Conclusion- WML represent areas with a complex molecular phenotype. From this and previous evidence, WML may arise through tissue ischemia but may also reflect the contribution of additional factors like blood-brain barrier dysfunction. Differential expression of genes in WM[L] compared to WM[C] indicate a "field effect" in the seemingly normal surrounding white matter. © 2009 American Heart Association, Inc.
Citation
Simpson, J. E., Hosny, O., Wharton, S. B., Heath, P. R., Holden, H., Fernando, M. S., …Ince, P. G. (2009). Microarray RNA expression analysis of cerebral white matter lesions reveals changes in multiple functional pathways. Stroke, 40(2), 369-375. https://doi.org/10.1161/STROKEAHA.108.529214
Journal Article Type | Article |
---|---|
Publication Date | Feb 1, 2009 |
Deposit Date | Dec 8, 2023 |
Journal | Stroke |
Print ISSN | 0039-2499 |
Publisher | Lippincott, Williams & Wilkins |
Volume | 40 |
Issue | 2 |
Pages | 369-375 |
DOI | https://doi.org/10.1161/STROKEAHA.108.529214 |
Public URL | https://hull-repository.worktribe.com/output/4455220 |
You might also like
Perceptual and conceptual processing of visual objects across the adult lifespan
(2019)
Journal Article
Two-decade change in prevalence of cognitive impairment in the UK
(2019)
Journal Article
Downloadable Citations
About Repository@Hull
Administrator e-mail: repository@hull.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search