Thesis

Investigating the neuroimmunomodulatory effects of 40Hz light flicker treatment in 5xFAD model of Alzheimer’s Disease

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Awarding institution
  • University of Strathclyde
Date of award
  • 2023
Thesis identifier
  • T16780
Person Identifier (Local)
  • 201962616
Qualification Level
Qualification Name
Department, School or Faculty
Abstract
  • AD is a chronic neurodegenerative condition affecting the aging population. Recently there has been global concern due to the rising prevalence of the disease and increasing financial burden of care. Despite the increasing prevalence of Alzheimer’s Disease (AD) there are currently no non-invasive treatments available for patients, with all available therapies only targeting the symptoms of disease and not the cause. Recently, a potential new form of treatment for AD has been gaining interest due to its non-invasive properties. Several studies have found that flickering a light at a 40Hz frequency was capable of reducing the disease pathology and improve memory retention in mouse models of AD via an unknown mechanism. We sought to unveil some of the mechanisms of this potential therapy. Using previously published methods we investigated the ability of 40Hz flickering light to reduce amyloid-β (Aβ) in the brains of 5xFAD mice- a transgenic mouse model of AD. We first used 9-month-old animals and treated for 1 hour a day for either 5 consecutive days or 15 days. In these 9-month-old animals we observed no significant changes in Aβ pathology (either plaque area or number) within the visual cortex (VC). We then changed the format of our treatment and reduced the ages of our animals to 4-5 months and revised our treatment equipment. At this reduced age we observed a significant reduction in total Aβ area alongside changes in gene expression in the VC for genes associated with the Aβ processing pathway, such as endogenous mouse APP and γ-secretase protein PSEN1. We then examined if the 40Hz light-flicker exhibited sex-dependent responses as previous studies have not examined sex-based differences. We observed that while some genes showed consistent changes between the sexes (PSEN1 & mAPP) some genes exhibited significant differences between male and female 5xFAD mice (BACE1 & Cst7), suggesting that the response was sex-dependent. Thus, 40Hz light flicker treatment reduced expression of Aβ in 4- 5-month-old 5xFAD mice as well as inducing significant changes in gene expression within the VC.
Advisor / supervisor
  • Gould, Gwyn W.
Resource Type
DOI
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