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The effect of in vitro derived microglia transplantation on astrocyte population in Alzheimer's disease
thesis
posted on 2016-10-27, 11:01 authored by Fraser SimpsonResearch into the pathogenesis of Alzheimer’s disease has largely been
dominated by the amyloid hypothesis, where neuroinflammation experienced in
Alzheimer’s was assumed to be a reaction to pathophysiological events. It has
recently been established that immune system actions contribute significantly to
Alzheimer’s pathogenesis. Activated microglia have long been documented as
a pathological characteristic of multiple neurodegenerative diseases, including
Alzheimer’s; recent genetic studies have linked the association of microglia
pathology with disease aetiology. Moreover, astrocytes experience multifaceted
region-specific changes in AD pathology as a result of neurotoxicity, whereby
these damaged cells have been shown to exacerbate β-amyloid pathology and
neurodegeneration. Studies have shown that transplanted microglia have
improved homeostatic functions in the brain resulting in a reduction of
neurotoxicity. Therefore, targeting microglia as a therapeutic or preventative
measure for Alzheimer’s disease provides promise for future therapies.
Consequently, using a transgenic APP/PS1 mouse model, this study
investigated whether transplantation of differentiated microglia had an effect on
astrocyte number and percentage area covered of the cortex and hippocampus.
In this study, transplanted microglia did not show to have a significant effect on
number and percentage area covered by astrocytes in either the cortex or
hippocampus when compared to a control group of APP/PS1 mice that did not receive treatment. Small increases were observed in all regions for both
parameters investigated, however, large standard deviations within the
treatment group were experienced. Therefore, optimisation of image
quantification techniques could provide a more accurate insight into the
regenerative effect of microglia transplantation on astrocytes, and potentially
confirm this non-significance. Finally, whilst analysis of astrocyte number and
percentage area covered shows some promise to providing insight into the
effect of microglia transplantation, further analysis into related variables, such
as number of transplanted microglia and astrocyte activity levels, to accompany
these findings could help determine this effect more precisely.
History
School
- Sport, Exercise and Health Sciences
Publisher
Fraser SimpsonPublisher statement
This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/Publication date
2015Notes
A Project submitted in the fulfilment of the requirements for Module PSP330 of the Degree of Master of Science in Musculoskeletal Sport Science and HealthLanguage
- en