Assessment of neurovascular coupling and cortical spreading depression in mixed mouse models of atherosclerosis and Alzheimer’s disease
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 haem...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/68242 |
| _version_ | 1811199409604526080 |
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| author | Osman Shabir Ben Pendry Llywelyn Lee Beth Eyre Paul S Sharp Monica A Rebollar David Drew Clare Howarth Paul R Heath Stephen B Wharton Sheila E Francis Jason Berwick |
| author_facet | Osman Shabir Ben Pendry Llywelyn Lee Beth Eyre Paul S Sharp Monica A Rebollar David Drew Clare Howarth Paul R Heath Stephen B Wharton Sheila E Francis Jason Berwick |
| author_sort | Osman Shabir |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T01:48:30Z |
| format | Article |
| id | doaj.art-92e57f89b041496cb62439a786902073 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:48:30Z |
| publishDate | 2022-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-92e57f89b041496cb62439a7869020732022-12-22T03:53:01ZengeLife Sciences Publications LtdeLife2050-084X2022-01-011110.7554/eLife.68242Assessment of neurovascular coupling and cortical spreading depression in mixed mouse models of atherosclerosis and Alzheimer’s diseaseOsman Shabir0https://orcid.org/0000-0001-7412-6966Ben Pendry1Llywelyn Lee2https://orcid.org/0000-0003-3449-9797Beth Eyre3Paul S Sharp4Monica A Rebollar5David Drew6Clare Howarth7https://orcid.org/0000-0002-6660-9770Paul R Heath8Stephen B Wharton9Sheila E Francis10Jason Berwick11Department of Infection, Immunity and Cardiovascular Disease (IICD), University of Sheffield Medical School, Royal Hallamshire Hospital, Sheffield, United Kingdom; Healthy Lifespan Institute (HELSI), University of Sheffield, Sheffield, United Kingdom; Neuroscience Institute, University of Sheffield, Sheffield, United KingdomSheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, United KingdomNeuroscience Institute, University of Sheffield, Sheffield, United Kingdom; Sheffield Neurovascular Lab, Department of Psychology, University of Sheffield, Sheffield, United KingdomNeuroscience Institute, University of Sheffield, Sheffield, United Kingdom; Sheffield Neurovascular Lab, Department of Psychology, University of Sheffield, Sheffield, United KingdomMedicines Discovery Catapult, Alderley Edge, United KingdomNeuroscience Institute, University of Sheffield, Sheffield, United Kingdom; Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, United KingdomDepartment of Infection, Immunity and Cardiovascular Disease (IICD), University of Sheffield Medical School, Royal Hallamshire Hospital, Sheffield, United KingdomHealthy Lifespan Institute (HELSI), University of Sheffield, Sheffield, United Kingdom; Neuroscience Institute, University of Sheffield, Sheffield, United Kingdom; Sheffield Neurovascular Lab, Department of Psychology, University of Sheffield, Sheffield, United KingdomSheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, United KingdomNeuroscience Institute, University of Sheffield, Sheffield, United Kingdom; Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, United KingdomDepartment of Infection, Immunity and Cardiovascular Disease (IICD), University of Sheffield Medical School, Royal Hallamshire Hospital, Sheffield, United Kingdom; Healthy Lifespan Institute (HELSI), University of Sheffield, Sheffield, United Kingdom; Neuroscience Institute, University of Sheffield, Sheffield, United KingdomHealthy Lifespan Institute (HELSI), University of Sheffield, Sheffield, United Kingdom; Neuroscience Institute, University of Sheffield, Sheffield, United Kingdom; Sheffield Neurovascular Lab, Department of Psychology, University of Sheffield, Sheffield, United KingdomNeurovascular 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.https://elifesciences.org/articles/68242NeurovascularatherosclerosisdementiaAlzheimer's diseasecomorbidityCSD |
| spellingShingle | Osman Shabir Ben Pendry Llywelyn Lee Beth Eyre Paul S Sharp Monica A Rebollar David Drew Clare Howarth Paul R Heath Stephen B Wharton Sheila E Francis Jason Berwick Assessment of neurovascular coupling and cortical spreading depression in mixed mouse models of atherosclerosis and Alzheimer’s disease eLife Neurovascular atherosclerosis dementia Alzheimer's disease comorbidity CSD |
| title | Assessment of neurovascular coupling and cortical spreading depression in mixed mouse models of atherosclerosis and Alzheimer’s disease |
| title_full | Assessment of neurovascular coupling and cortical spreading depression in mixed mouse models of atherosclerosis and Alzheimer’s disease |
| title_fullStr | Assessment of neurovascular coupling and cortical spreading depression in mixed mouse models of atherosclerosis and Alzheimer’s disease |
| title_full_unstemmed | Assessment of neurovascular coupling and cortical spreading depression in mixed mouse models of atherosclerosis and Alzheimer’s disease |
| title_short | Assessment of neurovascular coupling and cortical spreading depression in mixed mouse models of atherosclerosis and Alzheimer’s disease |
| title_sort | assessment of neurovascular coupling and cortical spreading depression in mixed mouse models of atherosclerosis and alzheimer s disease |
| topic | Neurovascular atherosclerosis dementia Alzheimer's disease comorbidity CSD |
| url | https://elifesciences.org/articles/68242 |
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