Androgen Modulation of CNS During Chronic Intermittent Hypoxia

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dc.contributor.advisorCunningham, Rebecca L.
dc.contributor.committeeMemberBarber, Robert C.
dc.contributor.committeeMemberCunningham, J. Thomas
dc.contributor.committeeMemberSchreihofer, Derek A.
dc.contributor.committeeMemberPlanz, John V.
dc.creatorSnyder, Brina D.
dc.creator.orcid0000-0001-6254-4941 (Snyder, Brina D.)
dc.date.accessioned2019-10-03T16:10:19Z
dc.date.available2019-10-03T16:10:19Z
dc.date.issued2018-05
dc.description.abstractThe underlying causes of age-related neurodegenerative diseases, such as Alzheimer's disease or Parkinson's disease, are unknown. It is likely conditions which contribute to an abundance of oxidative stress throughout life renders an individual more susceptible to late-life neurodegenerative processes. Sex differences are observed in the onset and prevalence of these diseases, suggesting estrogens and androgens influence these processes. This study investigates the early role of androgens under a known oxidative stressor, sleep apnea, which frequently goes untreated in the clinical population but is but is associated with an increased risk of late-life neurodegeneration. The hypoxic events of sleep apnea can be modeled in rats by the use of chronic intermittent hypoxia (CIH). Male rats are more susceptible to hypertensive effects of CIH, a key characteristic of sleep apnea. After one week of CIH treatment, they also exhibit oxidative stress and inflammation in circulation and in brain nuclei associated with early stages of Parkinson's disease or Alzheimer's disease. This led to the hypothesis that oxidative stress and inflammation would be associated with behavior deficits and these effects are mediated by androgens. Results show that oxidative stress and inflammatory dysregulation can be prevented by testosterone, but are highly exacerbated by testosterone's non-aromatizable metabolite, dihydrotestosterone (DHT). Administration of DHT also resulted in significant memory impairments under CIH. In the central nervous system, DHT significantly altered oxidative stress and pro-inflammatory signals, which may underlie its detrimental actions in an oxidative stress environment. There was also evidence of hypothalamic-pituitary-adrenal axis dysregulation, which can influence testosterone and circadian rhythms. These findings have broad implications for clinical populations with conditions which chronically increase oxidative stress and inflammation, while at the same time alter endocrine function. Conditions, such as untreated sleep apnea, may pose a latent risk for neurodegeneration and should be addressed early to prevent later detrimental effects.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/29699
dc.language.isoen
dc.subjectandrogens
dc.subjectmemory
dc.subjectneurodegeneration
dc.subjectoxidative stress
dc.subjectsleep apnea
dc.subjecttestosterone
dc.subject.meshNeurodegenerative Diseases
dc.subject.meshAndrogens
dc.subject.meshSleep Apnea Syndromes
dc.subject.meshOxidative Stress
dc.subject.meshDisease Models, Animal
dc.subject.meshTestosterone
dc.titleAndrogen Modulation of CNS During Chronic Intermittent Hypoxia
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentGraduate School of Biomedical Sciences
thesis.degree.disciplinePharmacology and Neuroscience
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameDoctor of Philosophy

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