Assessment of neurovascular coupling and cortical spreading depression in mixed mouse models of atherosclerosis and Alzheimer’s disease

eLife

David Drew¹  Sheila E Francis²  Osman Shabir²  Jason Berwick³  Clare Howarth³  Paul S Sharp⁴  Monica A Rebollar⁵  Stephen B Wharton⁵  Beth Eyre⁶  Llywelyn Lee⁶  Ben Pendry⁷  Paul R Heath⁷ 

[1] Department of Infection, Immunity and Cardiovascular Disease (IICD), University of Sheffield Medical School, Royal Hallamshire Hospital, Sheffield, United Kingdom;Department 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 Kingdom;Healthy 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 Kingdom;Medicines Discovery Catapult, Alderley Edge, United Kingdom;Neuroscience Institute, University of Sheffield, Sheffield, United Kingdom;Sheffield Institute for Translational Neuroscience (SITraN), 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 Kingdom;Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, United Kingdom;

关键词: Neurovascular;    atherosclerosis;    dementia;    Alzheimer's disease;    comorbidity;    CSD;    Mouse;    Atherosclerosis;    Alzheimer’s disease;    Neurovascular coupling;    Comorbidity;    CSD;   

DOI  :  10.7554/eLife.68242

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY