Surprising Behavioral and Neurochemical Enhancements in Mice with Combined Mutations Linked to Parkinson's Disease

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dc.contributor.advisorYu, Gangen
dc.contributor.committeeMemberGoldberg, Matthew S.en
dc.contributor.committeeMemberEisch, Amelia J.en
dc.contributor.committeeMemberHsieh, Jennyen
dc.contributor.committeeMemberJohnson, Jane E.en
dc.creatorHennis, Meghan Reillyen
dc.date.accessioned2016-01-05T19:27:01Z
dc.date.available2016-01-05T19:27:01Z
dc.date.created2013-12
dc.date.issued2013-11-29
dc.date.submittedDecember 2013
dc.date.updated2016-01-05T19:08:54Z
dc.description.abstractParkinson’s disease (PD) is the second most common neurodegenerative disease, after Alzheimer’s disease, afflicting over a million people in the United States alone. PD is an age-dependent disease that causes progressive death of dopamine-producing neurons in the substrantia nigra and depleted dopamine in the striatum. Loss of striatal dopamine results in locomotor symptoms such as bradykinesia, tremor, rigidity and postural instability. Although most forms of the disease are spontaneous, a subset of cases are genetic and humans lacking expression of either Parkin or DJ-1 develop PD. However, one limitation to studying PD is a lack of rodent models that recapitulate both the dopaminergic and motor symptoms as well as the age-dependent development of this disease. In fact, mice deficient for either one or both Parkin and DJ-1 genes have no dopaminergic neuron loss or deficiency in motor abilities. Therefore, I aimed to develop a rodent model of Parkinson’s disease that mimics the progressive symptoms observed in humans by crossing mice deficient for two genes causative for PD, Parkin and DJ-1. I also crossed mice deficient for Parkin and DJ-1 with mice deficient for glutathione peroxidase 1 (Gpx1), an antioxidant that is decreased in the brains of PD patients and increased in aged DJ-1 deficient mouse brains. Instead of the expected loss of dopamine, Parkin-/-DJ-1-/-Gpx1-/- mice exhibit increased striatal dopamine while Parkin-/-DJ-1-/- mice have increased serotonin in multiple brain regions. Additionally, motor phenotypes in these mice do not replicate symptoms observed in PD because Parkin-/-DJ-1-/- mice have an unexpected increase in latency to fall from the rotarod in the absence of other significant behavioral phenotypes. These results led me to examine the levels of proteins related to neurotransmitter synthesis and transport and to test non-motor behaviors in Parkin-/-DJ-1-/- mice. Behavior tests suggest that Parkin-/-DJ-1-/- mice have improved rotarod performance due to cognitive, rather than motor changes.en
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc933743762
dc.identifier.urihttps://hdl.handle.net/2152.5/2720
dc.language.isoenen
dc.subjectBiogenic Monoaminesen
dc.subjectCorpus Striatumen
dc.subjectGlutathione Peroxidaseen
dc.subjectParkinson Diseaseen
dc.titleSurprising Behavioral and Neurochemical Enhancements in Mice with Combined Mutations Linked to Parkinson's Diseaseen
dc.typeThesisen
dc.type.materialtexten
thesis.date.available2016-01-01
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineNeuroscienceen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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