Neuropsychiatric-like behavioural features of the Aldh2-/- mouse model of Alzheimer’s disease
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Authors
Czegledy, Nicole
Date
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thesis
Language
eng
Keyword
Alzheimer's disease , anxiety , depression , anhedonia , Deuterium-reinforced polyunsaturated fatty acids , Chronic unpredictable stress
Alternative Title
Abstract
Alzheimer’s disease (AD) is a complex, multifaceted neurodegenerative disorder characterized by progressive memory impairment and frequently presents with neuropsychiatric comorbidities, notably anxiety and depression. We have established Aldh2-/- mice as an oxidative stress-based model of age-related memory loss and cognitive impairment. However, very little is known about non-cognitive behavioural deficits, or if a sexual dimorphism exist in this model, as it does in humans. We performed a behavioural characterization of anxiety-related behaviours in response to aversive stimuli and depression-like behaviours related to despair and anhedonia. The performance of three cohorts at different time points (3-4, 7-8, and 11-12 months) was examined in a battery of behavioural tests consisting of an assessment of mobility and exploration (open field test), anxiety-related behaviour (light/dark box, elevated plus maze), and depression-related behaviour (forced swim test, tail suspension test, sucrose preference test). Compared to wild type mice, male and female Aldh2-/- mice exhibited increased anxiety-like behaviours that were first observed at 7 months of age. This anxious behaviour was prevented in Aldh2-/- mice treated with a deuterated polyunsaturated fatty acid (D-PUFA) diet for 10 weeks. Male Aldh2-/- mice exhibited a diminished preference for sucrose compared to wild type male mice. Dysfunction in the hypothalamic-pituitary (HPA) axis presents along with AD, anxiety, and depression. It was postulated that HPA dysfunction may underlie anxious and depressed behaviours in this model. This was evaluated using a mild chronic unpredictable stress (CUS) paradigm. The sucrose preference test and serum corticosterone analysis revealed no differences in response to chronic stress or acute stress between Aldh2-/- and wild type mice. These data reveal previously unreported behavioural abnormalities in the Aldh2-/- model of AD-like cognitive impairment.
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ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.