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dc.contributor.authorBaranowski, Bradley John
dc.date.accessioned2019-08-28T20:39:29Z
dc.date.available2019-08-28T20:39:29Z
dc.identifier.urihttp://hdl.handle.net/10464/14488
dc.description.abstractBeta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the rate limiting enzyme in the pathway responsible for beta-amyloid production, a pathological feature of Alzheimer’s Disease (AD). Exercise has been shown to reduce BACE1 activity, although the mechanisms responsible are unknown. Exercise has also been shown to increase brain-derived neurotrophic factor (BDNF) content and signalling, however whether this neurotrophic factor mediates the effects of exercise on BACE1 regulation requires further investigation. C57BL/6J male mice were placed on a low (LFD) or high fat diet (HFD) for 10-weeks. Following the intervention, the mice either remained sedentary or underwent an acute bout of treadmill running. Mice were euthanized and the prefrontal cortex and hippocampus were collected for analysis. The remaining sedentary mice (n=24) were used for an explant experiment where the tissue was directly treated with BDNF. The HFD reduced BDNF content in the hippocampus, however, an acute bout of exercise was able to significantly increase BDNF content in the prefrontal cortex. We further demonstrated that direct treatment with BDNF results in reductions in BACE1 activity in the prefrontal cortex. This novel finding demonstrates that BDNF can reduce BACE1 activity, independent of an exercise stimulus. Moreover, this finding shows for the first time, that there is a direct link between BDNF signalling and BACE1 regulation in this region of the brain. This highlights the viability of using exercise and BDNF to modulate BACE1 activity as a potential therapeutic intervention, without the negative consequences of drug-induced inhibitions.en_US
dc.language.isoengen_US
dc.publisherBrock Universityen_US
dc.subjectAlzheimer's Diseaseen_US
dc.subjectBDNFen_US
dc.subjectBACE1en_US
dc.subjectBrain Metabolismen_US
dc.subjectNeuropathologyen_US
dc.titleRole of acute exercise-induced brain-derived neurotrophic factor on beta-site amyloid precursor protein cleaving enzyme 1 and amyloid precursor protein processing in the brainen_US
dc.typeElectronic Thesis or Dissertationen_US
dc.degree.nameM.Sc. Applied Health Sciencesen_US
dc.degree.levelMastersen_US
dc.contributor.departmentApplied Health Sciences Programen_US
dc.degree.disciplineFaculty of Applied Health Sciencesen_US
refterms.dateFOA2021-08-18T01:31:38Z


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