The Effects of Antiretroviral Therapies on Oligodendrocyte Differentiation

Students

College

Faculty

Professor of Pathology

Project Summary

Over the past summer, I had the honor of being a research assistant at the Children’s Hospital of Philadelphia under the mentorship of Dr. Judith Grinspan and Dr. Kelly Jordan-Scuitto.

Around 50% of HIV+ patients have cognitive, motor, and behavioral differences, known as HAND (HIV-Associated Neurocognitive Disorders) even though they are treated with combined antiretroviral therapy (cART). cART is designed so that multiple stages of HIV replication are targeted at the same time, which means that the drugs are given in combination, so that the treatment is completely effective. However, imaging studies have shown that white matter loss was more prevalent among those HAND patients who went through cART. Since oligodendrocytes create myelin (white matter) in the brain and spinal cord, Dr. Grinspan’s lab studies the effects of ART drugs on oligodendrocyte differentiation (maturation).

In turn, I was assigned the drug Dolutegravir, which is used in a cocktail of drugs called Triumeq©️. In order to get the oligos themselves, I had to isolate them from a newborn rat pup and perform purification procedures, while also making sure they were healthy and growing. Once the cells were treated with the drug, after 72 hours I stained the cells with GalC, PLP, and DAPI antibodies and counted them. The data was then compiled and analyzed.

We discovered that Dolutegravir causes oligodendrocytes to not differentiate. This is important because that means the HIV+ patients that are taking this drug are not producing enough white matter, which could lead to HAND.

There were many times throughout this experience where I did not get the result I wanted. Sometimes, the cells did not grow properly or they did not stain. Even though it can be frustrating, it was comforting to know that this is something that all scientists go through, even ones who have been doing research their entire lives. I learned how to be patient with results and how to persevere through hardship.

Doing research allowed me to see the science in the books come to life. I learned a lot about the brain in a class I had taken over the spring semester, called Cognitive Neuroscience. To actually be able to use this knowledge and apply it was extremely enlightening. I am forever grateful for this experience and all that it has given me.