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Hippocampal transcriptome profiling reveals common disease pathways in chronic hypoperfusion and aging

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posted on 25.06.2021, 05:05 by Sang-Ha Baik, Sharmelee Selvaraji, David Y Fann, Luting Poh, Dong-Gyu Jo, Deron R Herr, Shenpeng ZhangShenpeng Zhang, Hyun Ah Kim, Michael De Silva, Mitchell KP Lai, Christopher Li-Hsian Chen, Grant DrummondGrant Drummond, Kah-Leong Lim, Christopher SobeyChristopher Sobey, Thiruma ArumugamThiruma Arumugam
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.

History

Publication Date

01/06/2021

Journal

Aging

Volume

13

Issue

11

Pagination

pp 14651—14674

Publisher

Impact Journals

ISSN

1945-4589

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The Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.

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