Honors Theses

Date of Award

Spring 5-8-2022

Document Type

Undergraduate Thesis

Department

Biology

First Advisor

Jason Paris

Relational Format

Dissertation/Thesis

Abstract

Although antiretroviral therapies have allowed people living with human immunodeficiency virus (HIV) to achieve normal life expectancies, they cannot cure HIV nor the neurological symptoms associated with infection, termed neuroHIV. NeuroHIV describes a myriad of neurological disorders including mood disorders (depression and anxiety), cognitive impairment, neuropathic pain, and motor disinhibition. The mechanisms by which HIV promotes neurological impairment are not known, but may involve actions of its neurotoxic proteins. One such protein that has been well-characterized is the HIV trans-activator of transcription (Tat). Tat exerts neurotoxic effects via various means, one of which is to activate microglia, the macrophages of the central nervous system, to induce a pro-inflammatory state in the brain. Marijuana (MJ) is more often smoked by HIV-positive individuals than the general population and is demonstrated in basic science models to reduce neuroinflammation. Whether MJ can attenuate HIV-induced neuroinflammation, thus alleviating some neuroHIV burden is not known and is the subject of this thesis. Previous literature suggests that delta-9-tetrahydrocannabinol (THC), one of most well-characterized components of MJ, has anti-inflammatory properties, making it a prime candidate for study. Herein, we exposed human microglia to Tat and a concurrent concentration-response curve of THC (0, 1, 10, or 100, or 1000 nM). We hypothesized that Tat would cause microglial activation that THC could ameliorate. Due to variance and a shortened time to conduct current experiments due to SARS-CoV-2-related disruptions, we did not observe a significant effect for Tat to activate microglia. However, we did observe THC (10 nM) to attenuate microglial activation compared to other concentrations. Thus, future work should further elucidate the potential anti-inflammatory constituents of MJ for their efficacy on HIV protein-mediated neuroinflammation.

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Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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