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Restoration of Cerebral and Systemic Microvascular Architecture in APP/PS1 Transgenic Mice Following Treatment with Liraglutide™

Kelly, Patricia, McClean, PL, Ackermann, Maximilian, Konerding, Moritz A., Holscher, Christian and Mitchell, CA (2015) Restoration of Cerebral and Systemic Microvascular Architecture in APP/PS1 Transgenic Mice Following Treatment with Liraglutide™. Microcirculation, 22 (2). pp. 133-145. [Journal article]

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URL: http://dx.doi.org/10.1111/micc.12186

DOI: 10.1111/micc.12186

Abstract

OBJECTIVE: Cerebral microvascular impairments occurring in AD may reduce Abeta peptide clearance and impact upon circulatory ultrastructure and function. We hypothesized that microvascular pathologies occur in organs responsible for systemic Abeta peptide clearance in a model of AD and that Liraglutide (Victoza((R))) improves vessel architecture. METHODS: Seven-month-old APP/PS1 and age-matched wild-type mice received once-daily intraperitoneal injections of either Liraglutide or saline (n = 4 per group) for eight weeks. Casts of cerebral, splenic, hepatic, and renal microanatomy were analyzed using SEM. RESULTS: Casts from wild-type mice showed regularly spaced microvasculature with smooth lumenal profiles, whereas APP/PS1 mice revealed evidence of microangiopathies including cerebral microanuerysms, intracerebral microvascular leakage, extravasation from renal glomerular microvessels, and significant reductions in both splenic sinus density (p = 0.0286) and intussusceptive microvascular pillars (p = 0.0412). Quantification of hepatic vascular ultrastructure in APP/PS1 mice revealed that vessel parameters (width, length, branching points, intussusceptive pillars and microaneurysms) were not significantly different from wild-type mice. Systemic administration of Liraglutide reduced the incidence of cerebral microanuerysms and leakage, restored renal microvascular architecture and significantly increased both splenic venous sinus number (p = 0.0286) and intussusceptive pillar formation (p = 0.0129). CONCLUSION: Liraglutide restores cerebral, splenic, and renal architecture in APP/PS1 mice.

Item Type:Journal article
Keywords:APP/PS-1, mouse, microvasculature, liraglutide, brain, vascular casting
Faculties and Schools:Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute > Nutrition Innovation Centre for Food and Health (NICHE)
Biomedical Sciences Research Institute > Genomic Medicine
Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Stratified Medicine
ID Code:37545
Deposited By: Professor Christopher Mitchell
Deposited On:02 May 2017 09:21
Last Modified:02 May 2017 09:21

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