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The effect of in vitro derived microglia transplantation on astrocyte population in Alzheimer's disease
thesisposted on 27.10.2016, 11:01 authored by Fraser Simpson
Research 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.
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