Research Paper Volume 13, Issue 11 pp 14651—14674
Hippocampal transcriptome profiling reveals common disease pathways in chronic hypoperfusion and aging
- 1 Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- 2 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- 3 Memory Aging and Cognition Centre, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- 4 Integrative Sciences and Engineering Programme, NUS Graduate School, National University of Singapore
- 5 School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea
- 6 Department of Biology, San Diego State University, San Diego, CA 92182, USA
- 7 Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, VIC, Australia
- 8 Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- 9 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
Received: December 8, 2020 Accepted: May 11, 2021 Published: June 1, 2021https://doi.org/10.18632/aging.203123
How to Cite
Copyright: © 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.
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.