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dc.contributor.authorBaik, Sang-Haen_US
dc.contributor.authorSelvaraji, Sharmeleeen_US
dc.contributor.authorFann, David Y.en_US
dc.contributor.authorPoh, Lutingen_US
dc.contributor.authorJo, Dong-Gyuen_US
dc.contributor.authorHerr, Deron R.en_US
dc.contributor.authorZhang, Shenpeng R.en_US
dc.contributor.authorKim, Hyun Ahen_US
dc.contributor.authorSilva, Michael Deen_US
dc.contributor.authorLai, Mitchell K. P.en_US
dc.contributor.authorChen, Christopher Li- Hsianen_US
dc.contributor.authorDrummond, Grant R.en_US
dc.contributor.authorLim, Kah-Leongen_US
dc.contributor.authorSobey, Christopher G.en_US
dc.contributor.authorArumugam, Thiruma V.en_US
dc.identifier.citationBaik, S., Selvaraji, S., Fann, D. Y., Poh, L., Jo, D., Herr, D. R., Zhang, S. R., Kim, H. A., Silva, M. D., Lai, M. K. P., Chen, C. L. H., Drummond, G. R., Lim, K., Sobey, C. G. & Arumugam, T. V. (2021). Hippocampal transcriptome profiling reveals common disease pathways in chronic hypoperfusion and aging. Aging, 13(11), 14651-14674.
dc.description.abstractVascular dementia (VaD) is a progressive cognitive impairment of vascular etiology. VaD is characterized by cerebral hypoperfusion, increased blood-brain barrier permeability and white matter lesions. An increased burden of VaD is expected in rapidly aging populations. The hippocampus is particularly susceptible to hypoperfusion, and the resulting memory impairment may play a crucial role in VaD. Here we have investigated the hippocampal gene expression profile of young and old mice subjected to cerebral hypoperfusion by bilateral common carotid artery stenosis (BCAS). Our data in sham-operated young and aged mice reveal an age-associated decline in cerebral blood flow and differential gene expression. In fact, BCAS and aging caused broadly similar effects. However, BCAS-induced changes in hippocampal gene expression differed between young and aged mice. Specifically, transcriptomic analysis indicated that in comparison to young sham mice, many pathways altered by BCAS in young mice resembled those already present in sham aged mice. Over 30 days, BCAS in aged mice had minimal effect on either cerebral blood flow or hippocampal gene expression. Immunoblot analyses confirmed these findings. Finally, relative to young sham mice the cell type-specific profile of genes in both young BCAS and old sham animals further revealed common cell-specific genes. Our data provide a genetic-based molecular framework for hypoperfusion-induced hippocampal damage and reveal common cellular signaling pathways likely to be important in the pathophysiology of VaD.en_US
dc.description.sponsorshipMinistry of Education (MOE)en_US
dc.description.sponsorshipNational Medical Research Council (NMRC)en_US
dc.rights© 2021 Baik et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.titleHippocampal transcriptome profiling reveals common disease pathways in chronic hypoperfusion and agingen_US
dc.typeJournal Articleen
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en_US
dc.description.versionPublished versionen_US
dc.subject.keywordsVascular Dementiaen_US
dc.description.acknowledgementThis work was supported by the National University of Singapore, Singapore National Medical Research Council Research Grants (NMRC-CBRG-0102/2016 and NMRC/OFIRG/0036/2017), Singapore Ministry of Education (MOE2017-T3-1-002) and La Trobe University, Australia.en_US
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