Khan, S, Yuldasheva, NY orcid.org/0000-0001-6213-6358, Batten, TFC et al. (3 more authors) (2018) Tau pathology and neurochemical changes associated with memory dysfunction in an optimised murine model of global cerebral ischaemia - A potential model for vascular dementia? Neurochemistry International, 118. pp. 134-144. ISSN 0197-0186
Abstract
Cerebral ischemia is known to be a major cause of death and the later development of Alzheimer's disease and vascular dementia. However, ischemia induced cellular damage that initiates these diseases remain poorly understood. This is primarily due to lack of clinically relevant models that are highly reproducible. Here, we have optimised a murine model of global cerebral ischaemia with multiple markers to determine brain pathology, neurochemistry and correlated memory deficits in these animals. Cerebral ischaemia in mice was induced by bilateral common carotid artery occlusion. Following reperfusion, the mice were either fixed with 4% paraformaldehyde or decapitated under anaesthesia. Brains were processed for Western blotting or immunohistochemistry for glial (GLT1) and vesicular (VGluT1, VGluT2) glutamate transporters and paired helical filament (PHF1) tau. The PHF1 tau is the main component of neurofibrillary tangle, which is the pathological hallmarks of Alzheimer's disease and vascular dementia. The novel object recognition behavioural assay was used to investigate the functional cognitive consequences in these mice. The results show consistent and selective neuronal and glial cell changes in the hippocampus and the cortex together with a significant reduction in GLT1 (***P < 0.001), VGluT1 (**P < 0.01) and VGluT2 (***P < 0.001) expression in the hippocampus in occluded mice as compared to sham-operated animals. These changes are associated with increased PHF1 (***P < 0.0001) protein and a significant impairment of performance (*p < 0.0006, N = 6/group) in the novel object recognition test. This model represents a useful tool for investigating cellular, biochemical and molecular mechanisms of global cerebral ischaemia and may be an ideal preclinical model for vascular dementia.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2018, Elsevier Ltd. All rights reserved. This is an author produced version of a paper published in Neurochemistry International. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Global cerebral ischaemia; Glutamate transporter; Tau protein; Memory deficit; Vascular dementia; Glial cells; Hippocampus; Stroke |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 18 Apr 2018 16:34 |
Last Modified: | 10 Apr 2019 00:43 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.neuint.2018.04.004 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:129758 |