Biphasic functional regulation in hippocampus of rat with chronic cerebral hypoperfusion induced by permanent occlusion of bilateral common carotid artery.
BACKGROUND
Chronic cerebral hypoperfusion induced by permanent occlusion of the bilateral common carotid artery (BCCAO) in rats has been commonly used for the study of Alzheimer's disease and vascular dementia. Despite the apparent cognitive dysfunction in rats with BCCAO, the molecular markers or pathways involved in the pathological alternation have not been clearly identified.


METHODS
Temporal changes (sham, 21, 35, 45, 55 and 70 days) in gene expression in the hippocampus of rats after BCCAO were measured using time-course microarray analysis. Gene Ontology (GO) and pathway analyses were performed to identify the functional involvement of temporally regulated genes in BCCAO.


RESULTS
Two major gene expression patterns were observed in the hippocampus of rats after BCCAO. One pattern, which was composed of 341 early up-regulated genes after the surgical procedure, was dominantly involved in immune-related biological functions (false discovery rate [FDR]<0.01). Another pattern composed of 182 temporally delayed down-regulated genes was involved in sensory perception such as olfactory and cognition functions (FDR<0.01). In addition to the two gene expression patterns, the temporal change of GO and the pathway activities using all differentially expressed genes also confirmed that an immune response was the main early change, whereas sensory functions were delayed responses. Moreover, we identified FADD and SOCS3 as possible core genes in the sensory function loss process using text-based mining and interaction network analysis.


CONCLUSIONS
The biphasic regulatory mechanism first reported here could provide molecular evidence of BCCAO-induced impaired memory in rats as well as mechanism of the development of vascular dementia.
Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea.
Jihye
J
Bang
Won Kyung
WK
Jeon
In Sun
IS
Lee
Jung-Soo
JS
Han
Bu-Yeo
BY
Kim
D000544:Alzheimer Disease / Q000209:etiology*; D000818:Animals; D002340:Carotid Artery Diseases / Q000150:complications*; D017536:Carotid Artery, Common / Q000473:pathology*; D016000:Cluster Analysis; D015140:Dementia, Vascular / Q000209:etiology*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006624:Hippocampus / Q000098:blood supply* / Q000378:metabolism*; D008297:Male; D058977:Molecular Sequence Annotation; D060066:Protein Interaction Maps; D051381:Rats; D015398:Signal Transduction