Microvascular dysfunction in a murine model of Alzheimer’s disease using intravital microscopy
Alzheimer’s disease (AD) is a complex neurocognitive disorder. Early theories of AD sought to identify a single unifying explanation underlying AD pathogenesis; however, evolving evidence suggests it is a multifactorial, systemic disease, involving multiple systems. Of note, vascular dysfunction, en...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2025.1482250/full |
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| author | Danielle Sidsworth Noah Tregobov Noah Tregobov Colin Jamieson Jennifer Reutens-Hernandez Joshua Yoon Geoffrey W. Payne Geoffrey W. Payne Stephanie L. Sellers Stephanie L. Sellers Stephanie L. Sellers Stephanie L. Sellers |
| author_facet | Danielle Sidsworth Noah Tregobov Noah Tregobov Colin Jamieson Jennifer Reutens-Hernandez Joshua Yoon Geoffrey W. Payne Geoffrey W. Payne Stephanie L. Sellers Stephanie L. Sellers Stephanie L. Sellers Stephanie L. Sellers |
| author_sort | Danielle Sidsworth |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is a complex neurocognitive disorder. Early theories of AD sought to identify a single unifying explanation underlying AD pathogenesis; however, evolving evidence suggests it is a multifactorial, systemic disease, involving multiple systems. Of note, vascular dysfunction, encompassing both cerebral and peripheral circulation, has been implicated in AD pathogenesis. This pilot study used intravital microscopy to assess differences in responsiveness of gluteal muscle arterioles between a transgenic AD mouse model (APP/PS1; Tg) and wild-type (C57BL/6; WT) mice to further elucidate the role of vascular dysfunction in AD. Arteriole diameters were measured in response to acetylcholine (10–9 to 10–5 M), phenylephrine (10–9 to 10–5 M), histamine (10–9 to 10–4 M) and compound 48/80 (10–9 to 10–3 M). Tg mice demonstrated a trend toward reduced vasodilatory response to acetylcholine with a significant difference at 10–5 M (36.91 vs. 69.55%: p = 0.0107) when compared to WT. No significant differences were observed with histamine, compound 48/80 or phenylephrine; however, a trend toward reduced vasoconstriction to phenylephrine was observed in Tg mice at higher concentrations. Mean net diameter change (resting to maximum) also differed significantly (p = 0.0365) between WT (19.11 μm) and Tg mice (11.13 μm). These findings suggest reduced vascular responsiveness may contribute to the systemic vascular deficits previously observed in AD models. Future research using diverse models and broader variables could further elucidate peripheral vascular dysfunction’s role in AD pathogenesis, including its impact on motor symptoms and disease progression. Such insights may inform the development of vascular-targeted therapeutic strategies. |
| format | Article |
| id | doaj-art-b2a187cd1a4e4414923b9298cb5180bc |
| institution | Kabale University |
| issn | 1663-4365 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj-art-b2a187cd1a4e4414923b9298cb5180bc2025-02-10T11:31:44ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652025-02-011710.3389/fnagi.2025.14822501482250Microvascular dysfunction in a murine model of Alzheimer’s disease using intravital microscopyDanielle Sidsworth0Noah Tregobov1Noah Tregobov2Colin Jamieson3Jennifer Reutens-Hernandez4Joshua Yoon5Geoffrey W. Payne6Geoffrey W. Payne7Stephanie L. Sellers8Stephanie L. Sellers9Stephanie L. Sellers10Stephanie L. Sellers11Division of Medical Sciences, University of Northern British Columbia, Prince George, BC, CanadaDepartment of Radiology, Faculty of Medicine, University of British Columbia, Vancouver, BC, CanadaCardiovascular Translational Laboratory, Providence Research and Centre for Heart Lung Innovation, Vancouver, BC, CanadaCardiovascular Translational Laboratory, Providence Research and Centre for Heart Lung Innovation, Vancouver, BC, CanadaBiochemistry and Molecular Biology Program, University of Northern British Columbia, Prince George, BC, CanadaCardiovascular Translational Laboratory, Providence Research and Centre for Heart Lung Innovation, Vancouver, BC, CanadaDivision of Medical Sciences, University of Northern British Columbia, Prince George, BC, CanadaUniversity of Northern British Columbia, Prince George, BC, CanadaCardiovascular Translational Laboratory, Providence Research and Centre for Heart Lung Innovation, Vancouver, BC, CanadaCentre for Cardiovascular Innovation, St. Paul’s and Vancouver General Hospital, Vancouver, BC, CanadaCentre for Heart Valve Innovation, St. Paul’s Hospital, University of British Columbia, Vancouver, BC, CanadaDilawri Cardiovascular Institute, Vancouver General Hospital, Vancouver, BC, CanadaAlzheimer’s disease (AD) is a complex neurocognitive disorder. Early theories of AD sought to identify a single unifying explanation underlying AD pathogenesis; however, evolving evidence suggests it is a multifactorial, systemic disease, involving multiple systems. Of note, vascular dysfunction, encompassing both cerebral and peripheral circulation, has been implicated in AD pathogenesis. This pilot study used intravital microscopy to assess differences in responsiveness of gluteal muscle arterioles between a transgenic AD mouse model (APP/PS1; Tg) and wild-type (C57BL/6; WT) mice to further elucidate the role of vascular dysfunction in AD. Arteriole diameters were measured in response to acetylcholine (10–9 to 10–5 M), phenylephrine (10–9 to 10–5 M), histamine (10–9 to 10–4 M) and compound 48/80 (10–9 to 10–3 M). Tg mice demonstrated a trend toward reduced vasodilatory response to acetylcholine with a significant difference at 10–5 M (36.91 vs. 69.55%: p = 0.0107) when compared to WT. No significant differences were observed with histamine, compound 48/80 or phenylephrine; however, a trend toward reduced vasoconstriction to phenylephrine was observed in Tg mice at higher concentrations. Mean net diameter change (resting to maximum) also differed significantly (p = 0.0365) between WT (19.11 μm) and Tg mice (11.13 μm). These findings suggest reduced vascular responsiveness may contribute to the systemic vascular deficits previously observed in AD models. Future research using diverse models and broader variables could further elucidate peripheral vascular dysfunction’s role in AD pathogenesis, including its impact on motor symptoms and disease progression. Such insights may inform the development of vascular-targeted therapeutic strategies.https://www.frontiersin.org/articles/10.3389/fnagi.2025.1482250/fullAlzheimer’s diseasemicrovascular dysfunctionmurine modelneurodegenerationvasoreactivityintravital microscopy |
| spellingShingle | Danielle Sidsworth Noah Tregobov Noah Tregobov Colin Jamieson Jennifer Reutens-Hernandez Joshua Yoon Geoffrey W. Payne Geoffrey W. Payne Stephanie L. Sellers Stephanie L. Sellers Stephanie L. Sellers Stephanie L. Sellers Microvascular dysfunction in a murine model of Alzheimer’s disease using intravital microscopy Frontiers in Aging Neuroscience Alzheimer’s disease microvascular dysfunction murine model neurodegeneration vasoreactivity intravital microscopy |
| title | Microvascular dysfunction in a murine model of Alzheimer’s disease using intravital microscopy |
| title_full | Microvascular dysfunction in a murine model of Alzheimer’s disease using intravital microscopy |
| title_fullStr | Microvascular dysfunction in a murine model of Alzheimer’s disease using intravital microscopy |
| title_full_unstemmed | Microvascular dysfunction in a murine model of Alzheimer’s disease using intravital microscopy |
| title_short | Microvascular dysfunction in a murine model of Alzheimer’s disease using intravital microscopy |
| title_sort | microvascular dysfunction in a murine model of alzheimer s disease using intravital microscopy |
| topic | Alzheimer’s disease microvascular dysfunction murine model neurodegeneration vasoreactivity intravital microscopy |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2025.1482250/full |
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