The Effects of Oxidative Stress and Testosterone on Dopamine Neuron Viability: Implications for Parkinson’s Disease

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dc.contributor.advisorCunningham, Rebecca L.
dc.contributor.committeeMemberSingh, Meharvan
dc.contributor.committeeMemberSchreihofer, Derek
dc.creatorHolmes, Shaletha S.
dc.date.accessioned2019-08-22T19:51:03Z
dc.date.available2019-08-22T19:51:03Z
dc.date.issued2015-12-01
dc.date.submitted2018-05-22T12:18:08-07:00
dc.description.abstractParkinson’s disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. Oxidative stress, mitochondrial dysfunction, inflammation and apoptosis are mechanisms implicated in Parkinson’s pathology. Interestingly, males have a higher incidence of PD than females. Therefore, the major male sex hormone, testosterone may play a role in oxidative stress-induced dopamine neurodegeneration and thus underlie the sex bias observed in PD. Oxidative stress, the imbalance of antioxidant mechanisms and reactive oxygen species, mediates downstream signaling of mitochondria dysfunction, inflammation and apoptosis. Oxidative stress can induce mitochondria dysfunction via calcium neurotoxicity, and oxidative stress can stimulate the pro-inflammatory mediators of NFkB and COX2. This activation of mitochondrial dysfunction and inflammation can trigger apoptosis in dopaminergic neurons. Therefore, it is hypothesized that under oxidative stress conditions, testosterone will induce dopaminergic neurodegeneration by increasing mitochondrial dysfunction and inflammation, leading to apoptosis in dopamine neurons. To test this hypothesis, a N27 dopaminergic cell line was treated with tert-butyl hydrogen peroxide followed by exposure to physiologically relevant concentrations of testosterone to assess cell viability, mitochondria function, calcium influx, inflammation, oxidative stress and apoptosis. These results show that testosterone, alone, increase calcium influx and acts as an oxidative stressor without affecting cell viability. However, under conditions of oxidative stress, testosterone decreases cell viability and exacerbates inflammation, resulting in increased apoptosis. These results indicate that testosterone, only in an oxidative stress environment, can increase pathological features associated with dopamine neurodegeneration in PD. In conclusion, these results suggest that a testosterone mediated mechanism may underlie the increased risk of PD for men compared to women.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/27103
dc.language.isoen
dc.provenance.legacyDownloads113
dc.subjectMedical Sciences
dc.subjectMedicine and Health Sciences
dc.subjecttestosterone
dc.subjectoxidative stress
dc.subjectdopamine neurons
dc.subjectParkinson's disease
dc.titleThe Effects of Oxidative Stress and Testosterone on Dopamine Neuron Viability: Implications for Parkinson’s Disease
dc.typeDissertation
dc.type.materialtext
thesis.degree.departmentGraduate School of Biomedical Sciences
thesis.degree.disciplineBiomedical Sciences
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameDoctor of Philosophy

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