DOI
https://doi.org/10.25772/JC7V-6559
Defense Date
2023
Document Type
Thesis
Degree Name
Master of Science
Department
Anatomy & Neurobiology
First Advisor
Dr. Pamela Knapp
Second Advisor
Dr. Babette Fuss
Third Advisor
Dr. Kurt Hauser
Abstract
Human immunodeficiency virus type-1 (HIV-1) has been greatly studied in recent decades. Combined anti-retroviral therapy (cART), the development of drug treatments such as maraviroc, and the wider availability of support for those in resource-rich environments have been instrumental in improving the prospects of people living with HIV (PLWH). It is well- documented that PLWH can suffer from a host of cognitive deficits collectively known as HIV- associated neurocognitive disorders (HAND). Moreover, the role of biological sex in the development of HAND and other cognitive deficits is still being studied. C-C chemokine receptor type 5 (CCR5) is one of the two major co-receptors for HIV entry into a host. In recent years, CCR5 has emerged as a potential contributor to cognitive decline even in the absence of HIV infection. Maraviroc is a prophylactic drug that prevents HIV from infecting new cells. Blockade of CCR5 using maraviroc may also improve cognitive functioning in virally- suppressed individuals. We hypothesized that CCR5 blockade would affect the population of select CCR5-positive cells within the hippocampus in a sex-dependent manner. Using a non- infectious HIV Tat-transgenic mouse model, we evaluated the proportions and CCR5- expression of microglia along and within the cell layers of the CA1-CA3 hippocampal axis.
We found sex differences regarding the populations of microglia. The proportions of microglia in the hippocampus did not change between males in different treatment groups, whereas changes were observed in females. The location of elevated CCR5 expression on microglia also differed between males and females. Short-term CCR5 blockade coincided with increased CCR5-positive microglia in both males and females, suggesting a potential side-effect of maraviroc being a paradoxical increase in CCR5 expression. Finally, changes in CCR5 expression along the layers of the hippocampus suggested that subtle differences in circuitry within male and female brains may contribute to the development of cognitive deficits.
Rights
© Ama S Boakye-Agyei
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-11-2023