Identification of Inflammatory, Metabolic, and Cell Survival Pathways Contributing to Cerebral Small Vessel Disease by Postmortem Gene Expression Microarray

Title:Identification of Inflammatory, Metabolic, and Cell Survival Pathways Contributing to Cerebral Small Vessel Disease by Postmortem Gene Expression Microarray

Volume: 13 Issue: 1

Author(s): Marie-Françoise Ritz, Caspar Grond-Ginsbach, Manja Kloss, Markus Tolnay, Felix Fluri, Leo H. Bonati, Christopher Traenka, Thomas Zeis, Nicole Schaeren-Wiemers, Nils Peters, Stefan Thomas Engelter and Philippe Alexandre Lyrer

Affiliation:

Keywords: Small vessel disease, vascular dementia, cDNA microarrays, inflammation, apoptosis, coagulation

Abstract: Cerebral small-vessel disease (SVD) is characterized by periventricular white matter (WM) changes and general brain atrophy. SVD is prevalent in elderly individuals and is frequently associated with the development of vascular dementia (VaD). Studies of the molecular basis of SVD are sparse. We have to gain further insight into the pathogenic mechanisms of SVD. Therefore, we compared gene expression patterns in the brains of SVD and control patients, in order to identify cellular pathways changed in diseased brains. We compared the expression of mRNA transcripts in postmortem, macroscopically normal-appearing human brain tissues isolated from frontal, temporal and occipital cortical and subcortical regions in 5 SVD and 5 non-SVD control patients. Significant expression changes were determined by fold change F>1.2 in either direction, and p<0.05. We identified 228 genes differentially expressed in cortex (89 up-, 139 down-regulated) and 555 genes in WM (223 up-, 332 down-regulated) in SVD patients. Pathway analyses revealed that upregulated genes were associated with inflammation and apoptosis in WM, suggesting active cell death. Downregulated genes were associated with coagulation and fatty and amino acids metabolisms. In the cortex, down-regulated genes were principally associated with neuronal functions. Our data revealed widespread changes in the transcriptome profiles in the cortex and WM of human SVD brains, with a predominance of changes in WM. We provide for the first time a comprehensive view of the molecular alterations in human SVD brains that seem to contribute to the neuropathogenesis of SVD.

Cite this article as:

Ritz Marie-Françoise, Grond-Ginsbach Caspar, Kloss Manja, Tolnay Markus, Fluri Felix, Bonati H. Leo, Traenka Christopher, Zeis Thomas, Schaeren-Wiemers Nicole, Peters Nils, Engelter Thomas Stefan and Lyrer Alexandre Philippe, Identification of Inflammatory, Metabolic, and Cell Survival Pathways Contributing to Cerebral Small Vessel Disease by Postmortem Gene Expression Microarray, Current Neurovascular Research 2016; 13 (1) . https://dx.doi.org/10.2174/1567202612666151027151025