Background: Cerebral small vessel disease (SVD) is an important cause of stroke and vascular cognitive impairment (VCI), leading to subcortical ischemic vascular dementia. As a hereditary form of SVD with early onset, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) represents a pure form of SVD and may thus serve as a model disease for SVD. To date, underlying molecular mechanisms linking vascular pathology and subsequent neuronal damage in SVD are incompletely understood.
Objective: We performed comparative transcriptional profiling microarray and proteomic analyses on post-mortem frontal lobe specimen from 2 CADASIL patients and 5 non neurologically diseased controls in order to identify dysregulated pathways potentially involved in the development of tissue damage in CADASIL.
Methods: Transcriptional microarray analysis of material extracted from frontal grey and white matter (WM) identified subsets of up- or down-regulated genes enriched into biological pathways mostly in WM areas. Proteomic analysis of these regions also highlighted cellular processes identified by dysregulated proteins.
Results: Discrepancies between proteomic and transcriptomic data were observed, but a number of pathways were commonly associated with genes and corresponding proteins, such as: “ribosome” identified by upregulated genes and proteins in frontal cortex or “spliceosome” associated with down-regulated genes and proteins in frontal WM.
Conclusion: This latter finding suggests that defective expression of spliceosomal components may alter widespread splicing profile, potentially inducing expression abnormalities that could contribute to cerebral WM damage in CADASIL.
[http://dx.doi.org/10.1161/01.STR.0000189696.70989.a4] [PMID: 16269644]
[http://dx.doi.org/10.1212/01.wnl.0000216271.96364.50] [PMID: 16717211]
[http://dx.doi.org/10.1007/BF00571504] [PMID: 7676806]
[http://dx.doi.org/10.1159/000356789] [PMID: 24401164]
[http://dx.doi.org/10.2174/1567202612666151027151025] [PMID: 26503025]
[http://dx.doi.org/10.1152/ajpcell.2001.280.6.C1645] [PMID: 11350761]
[http://dx.doi.org/10.1161/01.ATV.0000134298.25489.92] [PMID: 15178554]
[http://dx.doi.org/10.1002/(SICI)1097-4547(19990715)57:2<255:AID-JNR11>3.0.CO;2-6] [PMID: 10398303]
[http://dx.doi.org/10.1128/MCB.25.14.5834-5845.2005] [PMID: 15988001]