Investigating Octopaminergic/Tyraminergic Signaling and Tau Toxicity in a Drosophila Model of Alzheimer's Disease

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dc.contributor.advisorColodner, Kenneth J.
dc.contributor.authorChai, Cynthia
dc.date.accessioned2014-06-23T12:44:00Z
dc.date.available2014-06-23T12:44:00Z
dc.date.gradyear2014en_US
dc.date.issued2014-06-23
dc.description.abstractAlzheimer’s disease (AD) is a neurodegenerative disease characterized by the presence of filamentous tau inclusions. Clinical studies have shown that the locus coeruleus (LC), the main source of noradrenaline in the brain displays prominent Tau pathology and extensive cell loss in AD. However, the interaction between noradrenergic signaling and Tau toxicity in the diseased brain has been largely understudied. To determine if noradrenergic signaling mediates Tau toxicity, I utilized the fruit fly, Drosophila melanogaster, to examine the effects of modulating signaling of the invertebrate homologs of noradrenaline and adrenaline, octopamine and tyramine, on Tau toxicity. To this end, I expressed human wild-type Tau in the Drosophila eye in conjunction with genetic manipulation of octopaminergic and tyraminergic signaling. Using this paradigm, both suppressors and enhancers of Tau toxicity were identified. Based on previous research, I predicted that a reduction in octopaminergic/tyraminergic signaling would result in an enhancement of Tau toxicity. Contrary to my hypothesis, I found that a reduction of Tyramine 1 receptor (TYR1-R) signaling suppresses Tau toxicity. The results of this study implicate TYR1-R signaling as a mediator of Tau toxicity and suggest a novel role for biogenic amines in the regulation of mechanisms of AD pathogenesis.en_US
dc.description.sponsorshipNeuroscience and Behavioren_US
dc.identifier.urihttp://hdl.handle.net/10166/3528
dc.language.isoen_USen_US
dc.rights.restrictedrestricteden_US
dc.subjectneuroscienceen_US
dc.subjectDrosophila melanogasteren_US
dc.subjectAlzheimer's diseaseen_US
dc.subjectoctopamineen_US
dc.subjecttyramineen_US
dc.titleInvestigating Octopaminergic/Tyraminergic Signaling and Tau Toxicity in a Drosophila Model of Alzheimer's Diseaseen_US
dc.typeThesis
mhc.degreeUndergraduateen_US
mhc.institutionMount Holyoke College

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