Browsing by Subject "Androgens"
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Item Androgen Modulation of CNS During Chronic Intermittent Hypoxia(2018-05) Snyder, Brina D.; Cunningham, Rebecca L.; Barber, Robert C.; Cunningham, J. Thomas; Schreihofer, Derek A.; Planz, John V.The 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.Item The role of lipid rafts in androgen's neurotoxic effects(2021-08) Fadeyibi, Oluwadarasimi M.; Cunningham, Rebecca L.; Cunningham, J. Thomas; Sumien, Nathalie; Yan, Liang-Jun; Park, InWooSex differences have been observed in multiple oxidative stress (OS) associated neurodegenerative diseases. Androgens, the major male sex hormone, through a membrane androgen receptor (mAR) localized to lipid rafts in the plasma membrane exacerbates OS. The goal of this study is to determine if interfering with mAR localization to cholesterol-rich lipid rafts decreases androgen induced neurotoxicity under OS environments. We hypothesize that cholesterol-rich caveolar lipid rafts are necessary for androgens to induce OS generation in neurons via the mAR localized within the plasma membrane. Nystatin was used to deplete cholesterol-rich caveolar lipid rafts in N27 cells prior to testosterone exposure in oxidative stressed N27 cells. Cell viability and protein analysis of OS, apoptosis, and mAR localization were conducted. Our results show that the loss of lipid rafts blocked androgen-induced OS in cells by decreasing the localization of mAR to caveolar lipid rafts. These results are consistent with our clinical findings that showed a relationship between hyperlipidemia and androgens on dementia in men but not women.