Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.770532
Title: Vascular correlates in a mouse model of Alzheimer’s disease
Author: Kelly , Patricia
ISNI:       0000 0004 7653 1094
Awarding Body: Ulster University
Current Institution: Ulster University
Date of Award: 2016
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Abstract:
Aims During the progression of Alzheimer’s disease (AD), recognisable impairments in the vasculature are considered to be confined to the brain and occur solely as a consequence of the neuropathology associated with the disease. Here we use the microvascular corrosion casting technique with scanning electron microscopy (SEM) to recreate and examine the cerebral and systemic vascular ultrastructure of the APPswe/PS1dE9 (APP/PS1) murine model of AD. Our aims are to determine whether cerebral and systemic vascular ultrastructural impairments coincide with the neuropathology of 9-month old APP/PS1 mice and that liraglutide (Victoza®) treatment can restore vascular ultrastructure (chapter 3). In addition, we test whether cerebral and systemic vasculature ultrastructural impairments exist prior to cognitive dysfunction in 4-5 month old APP/PS1 mice (chapter 4) and that liraglutide treatment can slow onset ot neuropathology in 6-z month old APP/PS1 mice (chapter 5). I he hypothesis tested is that cerebral and systemic vascular ultrastructural impairments precede the onset of cognitive dysfunction in APP/PS1 mice representing a therapeutic target to slow the development of disease progression in this AD model. Methods In chapter 3; seven-month old male wild-type and APP/PS1 mice (n=4) received once-daily intraperitoneal injections of either liraglutide [25 nmol/kg body weight (bw)] or saline (0.9% w/v NaCI) for eight weeks. Following treatment, each nine-month old animal received an intraperitoneal injection of heparin prior to non­recovery anaesthesia (ketamine [100 mg/kg bw]; xylazine [16 mg/kg bw]) and a sequential transcardiac perfusion of saline, 2.5% glutaraldehyde and microvascular casting solution. Following a 12-hour polymerisation, the casted organs were dissected free, macerated in 5-7.5% KOH, repeatedly washed with dd.H20, air-dried and sputter-coated in Pd/Au prior to evaluation by SEM. In chapter 4; the body weight of four-to-five month old wild-type and APP/PS1 mice (n=6) in addition to the recognition memory (n=11), brain weight (n=6), numbers of thioflavin-S positive plaques (n=6), fasting intraperitoneal glucose tolerance (n=11) and urinary albumin creatinine ratios (uACR; n=5) were determined as well as microvascular corrosion casting (r?=6). In chapter 5; 4-5 month old wild-type and APP/PS1 transgenic mice received once-daily injections of either liraglutide [25 nmol/kg bw; n=6) or saline (0.9% w/v NaCI; n=5) for eight weeks prior to the assessment of body weight, food intake, recognition memory, fasting intraperitoneal glucose tolerance, serum albumin, brain weight and numbers of cerebral thioflavin-S positive plaques.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.770532  DOI: Not available
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