Shabir, O., Pendry, B., Lee, L. et al. (9 more authors) (2022) Assessment of neurovascular coupling and cortical spreading depression in mixed mouse models of atherosclerosis and Alzheimer’s disease. eLife, 2022 (11). e68242. ISSN 2050-084X
Abstract
Neurovascular coupling is a critical brain mechanism whereby changes to blood flow accompany localised neural activity. The breakdown of neurovascular coupling is linked to the development and progression of several neurological conditions including dementia. In this study, we examined cortical haemodynamics in mouse preparations that modelled Alzheimer’s disease (J20-AD) and atherosclerosis (PCSK9-ATH) between 9 and 12 m of age. We report novel findings with atherosclerosis where neurovascular decline is characterised by significantly reduced blood volume, altered levels of oxyhaemoglobin and deoxyhaemoglobin, in addition to global neuroinflammation. In the comorbid mixed model (J20-PCSK9-MIX), we report a 3 x increase in hippocampal amyloid-beta plaques. A key finding was that cortical spreading depression (CSD) due to electrode insertion into the brain was worse in the diseased animals and led to a prolonged period of hypoxia. These findings suggest that systemic atherosclerosis can be detrimental to neurovascular health and that having cardiovascular comorbidities can exacerbate pre-existing Alzheimer’s-related amyloid-plaques.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2021 Shabir et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. (http://creativecommons.org/licenses/by/4.0/) |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > Department of Psychology (Sheffield) |
Funding Information: | Funder Grant number BRITISH HEART FOUNDATION PG/20/10010 WELLCOME TRUST (THE) 105586/Z/14/Z ALZHEIMER'S RESEARCH UK ARUK-IRG2014-10 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 05 Jan 2022 17:43 |
Last Modified: | 11 Jan 2022 17:26 |
Status: | Published |
Publisher: | eLife Sciences Publications Ltd |
Refereed: | Yes |
Identification Number: | 10.7554/eLife.68242 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:181936 |