The Protective Role of Estrogen on HIV-1 Mediated Neurotoxicity

Licamied, Macklin (2019) The Protective Role of Estrogen on HIV-1 Mediated Neurotoxicity. Undergraduate thesis, under the direction of Jason Paris from BioMolecular Sciences, The University of Mississippi.

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Abstract

The prevalence of HIV among men have been in a steady inclination over the last several decades, yet the accelerated infection rate among older women is considerably concerning. Not only does the HIV virus affect the immune system but it also affects the central nervous system. One of its viral proteins, Tat, acts as an excitotoxin and disrupts the cell’s membrane potential by increasing the concentration of Ca2+ inside the cell. This influx of calcium ions leads to apoptosis and secretion of the cell’s contents into the surrounding area. Macrophages, along with other innate immune components, gather and induce the release of cytokines or chemokines. However, it has been discovered that estrogens can be used to attenuate these harmful neurotoxic effects. Acknowledging that women over the age of 50 are undergoing menopause, the body’s natural levels of estrogen begin to decline. We hypothesized that estradiol (acting at estrogen receptor α or β) would attenuate Tat-mediated formation of reactive oxygen species (ROS), neurotoxicity, and cytokine production in differentiated SH-SY5Y human neuroblastoma cells and primary murine mixed glial cultures. Our findings suggest that any concentration of estradiol (0.01-10 nM) could attenuate Tat-mediated ROS, but cell death involving was not influenced. Estrogen receptor α agonism appeared more effective than β. Tat was also observed to increase cytokine expression. This information may be particularly important for medical treatments concerning aged HIV-infected women. Restoring estrogens post-menopausally may improve the prevalence of HIV-related neurocognitive impairments that occur with age.

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