Do antiretroviral drugs modulate oligodendrocyte differentiation?

Adriana working at wet lab bench




Research Professor of Neurology

Project Summary

 For people living with HIV+, the current and most common course of treatment is a strict regimen of antiretroviral drugs. Although sustained antiretroviral drug therapy (ART) has the ability to suppress viral loads in patients to undetectable levels, the therapy itself is not a cure for HIV. HIV+ patients are expected to be on ART their entire lives to prevent viral transmission, which enables the drugs to spend a lot of time interacting with various parts of the body. There isn’t a clear understanding of how these drugs impact the brain, development, and overall health. Studies on post-mortem brains of HIV+ patients on ART drugs revealed deficiencies in white matter, a part of the brain that is rich in myelin. Myelin is made of mature oligodendrocytes and can be adversely affected for a number of reasons, including oligodendrocyte cell death or inhibited oligodendrocyte precursor cell (OPC) maturation. For this reason, the purpose of my research was to determine the individual impact of the ART drugs Darunavir and Emtricitabine on oligodendrocyte maturation. To determine the effects of these drugs, I cultured OPCs and treated them using a paradigm that took roughly two weeks. I then analyzed protein levels with immunostaining and western blotting.

My time spent over the summer on this research project was enlightening, but since it was one of my first experiences working in a lab, everything came with a steep learning curve. New terminology and complex issues were constantly being hurled at me, and much of my summer was spent learning how to solve scientific dilemmas and navigate this academic research environment. I learned how to apply classroom knowledge to research labs, but more importantly, I improved my ability to interpret data, which will be applicable to a variety of things I will do in the future. Although wet lab skills and technique weren’t easy to master, many of the problems I faced were actually when I was designing the structure of my project. Due to the fundamental course of HIV+ progression and treatment, it’s quite difficult to accurately simulate antiretroviral therapy since most patients, if not all, receive a “cocktail” of various different kinds of antiretroviral drugs. Therefore, the concentration of ART drugs that patients are receiving is not constant. To account for this variability in dosages, I treated cultures with low, medium, and high dosages. In addition to the complex nature of treatment, OPCs themselves are not simple cells. Previous studies have demonstrated the potential of OPCs to differentiate into not only mature oligodendrocytes, but also astrocytes. There are signaling cascades, such as the bone morphogenetic protein (BMP) pathway, that are known to induce astrocyte differentiation when activated. Because the presence of these pathways means ART drugs could potentially be inducing astrocyte differentiation, I decided it was relevant to stain for proteins indicative of astrocyte growth. Although by the end of my 10 weeks, my data wasn’t entirely conclusive, my ability to contribute to the advancement of HIV+ treatment is something that I feel I can proudly say will have a positive impact on patients and academia alike.