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Title: Hippocampal transcriptome profiling reveals common disease pathways in chronic hypoperfusion and aging
Authors: Baik, Sang-Ha
Selvaraji, Sharmelee
Fann, David Y.
Poh, Luting
Jo, Dong-Gyu
Herr, Deron R.
Zhang, Shenpeng R.
Kim, Hyun Ah
Silva, Michael De
Lai, Mitchell K. P.
Chen, Christopher Li- Hsian
Drummond, Grant R.
Lim, Kah-Leong
Sobey, Christopher G.
Arumugam, Thiruma V.
Keywords: Science::Medicine
Issue Date: 2021
Source: Baik, 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.
Project: NMRC-CBRG-0102/2016
Journal: Aging
Abstract: Vascular 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.
ISSN: 1945-4589
DOI: 10.18632/aging.203123
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.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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