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Full-Text Articles in Neuroscience and Neurobiology
Lysosomes Mediate Rab27b-Dependent Secretion Of Beta-Amyloid, Shany Lahan
Lysosomes Mediate Rab27b-Dependent Secretion Of Beta-Amyloid, Shany Lahan
Electronic Thesis and Dissertation Repository
Extracellular deposition of beta-Amyloid (Aβ) is an early event in Alzheimer’s disease development. However, it is not known how Aβ is secreted. Lysosomes readily undergo calcium-dependent exocytosis, a process that relies on small GTPase Rab27b. In addition, lysosomal enzymes have been found within extracellular amyloid plaques. We hypothesized that lysosomes mediate Rab27b-dependent exocytosis of Aβ. Neuro-2a cells were transfected with wild-type or mutant Rab27b constructs and/or a lysosomal marker. Cells were incubated with Aβ monomers and imaged using a confocal microscope before and after stimulation of calcium-dependent exocytosis. We observed a significant decrease in lysosome and Aβ co-localization post-treatment in …
Cerebral Lactate Metabolism And Memory: Implications For Alzheimer's Disease, Richard Andrew Harris
Cerebral Lactate Metabolism And Memory: Implications For Alzheimer's Disease, Richard Andrew Harris
Electronic Thesis and Dissertation Repository
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by amyloid plaques that are comprised of aggregated amyloid-beta peptides. These toxic proteins promote mitochondrial dysfunction and neuronal cell death. A shift in metabolism away from oxidative phosphorylation and toward aerobic glycolysis, with the concomitant production of lactate, affords neurons a survival advantage against amyloid-beta toxicity. Recent evidence now suggests that aerobic glycolysis in the brain plays a critical role in supporting synaptic plasticity, learning, and memory. However, the role of aerobic glycolysis and lactate metabolism in AD-mediated cognitive decline is unknown. My objective was to test the hypotheses that aerobic glycolysis …
Determining Attention Deficits In Mouse Models Of Alzheimer’S Disease Using Touchscreen Systems, Talal Masood
Determining Attention Deficits In Mouse Models Of Alzheimer’S Disease Using Touchscreen Systems, Talal Masood
Electronic Thesis and Dissertation Repository
Behavioural testing in mouse models of Alzheimer’s disease (AD) suffers from lack of standardization and reproducibility issues between laboratories. In order to solve this, a touchscreen system has been developed for mice based on the CANTAB. There are several cognitive dysfunctions that occur due to AD, including deficits in attention that can be tested using the touchscreens. In this study, we tested two mouse models of familial AD (5xFAD and 3xTG) with mutations that lead to an accelerated rate of amyloidosis. Both male and female mice were tested at two separate locations in order to test for the reproducibility of …
Investigating The Pathological Response To Beta Amyloid Toxicity In Rats: The Role Of Age And The Antioxidant Catalase-Skl, Hayley J. Nell
Investigating The Pathological Response To Beta Amyloid Toxicity In Rats: The Role Of Age And The Antioxidant Catalase-Skl, Hayley J. Nell
Electronic Thesis and Dissertation Repository
Accumulation of beta-amyloid (Aβ) in the brain is a major contributor to the cellular pathology and cognitive impairment observed in Alzheimer’s disease (AD). In part, Aβ exerts its toxic effects by increasing reactive oxygen species (ROS) and neuroinflammation in the brain. Aging, a major risk factor for AD is also associated with increased production of ROS. This study investigated the age-related pathological response to Aβ toxicity and examined whether catalase-SKL(CAT-SKL), a genetically engineered derivative of the peroxisomal antioxidant enzyme catalase, is able to reduce Aβ toxicity. Bilateral intracerebroventricular (icv) injections of the Aβ25-35 peptide was used to model Aβ …
An Investigation Into The Combined Effects Of Β-Amyloid Toxicity And Cerebral Ischemia On The Pathological Expression Of Gangliosides., Jeffrey D. Hepburn
An Investigation Into The Combined Effects Of Β-Amyloid Toxicity And Cerebral Ischemia On The Pathological Expression Of Gangliosides., Jeffrey D. Hepburn
Electronic Thesis and Dissertation Repository
Identifying mechanisms underlying the synergistic pathological interaction between stroke and Alzheimer’s disease (AD) can effectively guide future therapeutic strategies for these highly co-morbid conditions. Aberrant ganglioside expression marked by the pathological accumulation of ganglioside GM3 is common to stroke and AD, yet it is unclear whether GM3 is synergistically enhanced in a comorbid model, or if GM3 is a viable therapeutic target. Adult male Wistar rats received a unilateral ischemic striatal infarct via endothelin-1 (ET-1) injection alone or in combination with bilateral intracerebroventricular injection of the β-Amyloid 25-35 peptide (Aβ) to induce generalized Aβ toxicity (Aβ/ET-1). Animals were sacrificed after …