A single systemic inflammatory insult causes acute motor deficits and accelerates disease progression in a mouse model of human tauopathy

Alzheimer's and Dementia: Translational Research and Clinical Interventions - Tập 5 - Trang 579-591 - 2019
Megan Torvell1,2,3,4, David W. Hampton1,2, Peter Connick5, Alasdair M.J. MacLullich6, Colm Cunningham7, Siddharthan Chandran1,2,3,5
1Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
2Euan MacDonald Centre for MND Research, University of Edinburgh, Edinburgh, UK
3UK Dementia Research Institute at University of Edinburgh, Edinburgh, UK
4UK Dementia Research Institute at University of Cardiff, Cardiff, UK
5The Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, Midlothian, UK
6Edinburgh Delirium Research Group, Geriatric Medicine, University of Edinburgh, Edinburgh, UK
7Trinity Biomedical Sciences Institute and Trinity College Institute of Neuroscience, School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland

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AbstractIntroductionNeuroinflammation, which contributes to neurodegeneration, is a consistent hallmark of dementia. Emerging evidence suggests that systemic inflammation also contributes to disease progression.MethodsThe ability of systemically administered lipopolysaccharide (LPS ‐ 500 μg/kg) to effect acute and chronic behavioural changes in C57BL/6 and P301S tauopathy mice was assessed. Markers of pathology were assessed in the brain and spinal cord.ResultsP301S mice display regional microgliosis. Systemic LPS treatment induced exaggerated acute sickness behaviour and motor dysfunction in P301S mice compared with wild‐type controls and advanced the onset and accelerated chronic decline. LPS treatment was associated with increased tau pathology 24 hours after LPS injection and spinal cord microgliosis at the end stage.DiscussionThis is the first demonstration that a single systemic inflammatory episode causes exaggerated acute functional impairments and accelerates the long‐term trajectory of functional decline associated with neurodegeneration in a mouse model of human tauopathy. The findings have relevance to management of human dementias.

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Alzheimer's and Dementia: Translational Research and Clinical Interventions

Tập 5

579-591

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