Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Dr. Shawn Whitehead and Dr. David Cechetto

Abstract

Alzheimer’s disease (AD) is the most common form of dementia and is characterized by progressive neuronal loss and cognitive decline. Currently, no therapeutic treatments are available and our understanding of the disease progression is still unclear. Amyloid beta oligomers (AβO) are potent neurotoxic proteins and may be a potential initiator of the progression of AD. The purpose of this project was to identify the spatial and temporal consequences of injecting AβO into the rat brain by evaluating pathological and behavioural outcomes. We hypothesized that injecting AβO into the rat brain will result in microglial response as well as behavioural and cognitive deficits. Synthetic AβO were used for this study and characterized by western blot. AβO were injected intracerebroventricularly (ICV) into the rat brain and a timeline was established at 1, 3, 7 and 21-days post-surgery. Immunohistochemistry was used to stain the sections for AβO deposition, microglial response, and cholinergic neurons. Behavioural analyses included the Morris Water Maze task for spatial learning and memory and open field for exploratory and anxiety-like behaviours. Our data showed that ICV injections of AβO resulted in AβO deposition in the walls of ventricles and a subtle and transient deficit in spatial learning and memory as well as anxiety-like behaviours. No differences in microglial response within the hippocampus, basal forebrain, corpus callosum, internal capsule, and fimbriae of hippocampus were observed. In addition, no significant differences were observed with cholinergic neuron numbers in the basal forebrain (medial septum, vertical and horizontal diagonal bands of Broca). Overall, our results indicate that injection of AβO into the rat brain may be an alternative, non-transgenic strategy to investigate the effects of AβO in an in vivo model.

Available for download on Thursday, November 30, 2017


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