# Microglial modulation of neurocircuits in HIV/cocaine comorbidity

> **NIH NIH R01** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 2024 · $653,642

## Abstract

Project Summary:
Despite the success of combination antiretroviral therapy (cART), a significant proportion of infected individuals
exhibiting neurocognitive decline, and a prior history of substance use disorder (SUD) may result in an
exacerbated rate of decline. Thus, prior drug history may be clinically significant in the treatment of
neurological HIV-1 infection. The specific aims of the project are: 1) To define the dendritic “spine-
targeted” - microglial interactions which produce HIV-1/psychostimulant-induced synaptodendritic
loss and spine dysmorphology. Dendritic spine loss is a key pathology of HAND; however, the underlying
mechanisms remain largely uncharacterized. We will investigate whether HIV-infected microglia play a key role
in spine loss/dysmorphology using an in vitro HIV infection model and psychostimulant drug exposures in sex-
specified brain cell cultures. 2) To establish whether a history of psychostimulant abuse drives an
accelerated progression of microglial dysfunction and dendritic spine alterations following HIV
infection. Dopamine will be assessed both prior to and after EcoHIV-infection in animals with or without a
history of cocaine self-administration. The mechanisms by which HIV-infected microglia produce dopaminergic
circuit dysfunction will be critically tested using proviral gene excision techniques; cART, and SABV are integral
factors of the design. 3) To establish executive function “choice” deficits in EcoHIV-infected animals,
and the role of microglial HIV infection, following psychostimulant self-administration. We will establish
prior drug history and HIV-1 infection as variables that influence the effect of fronto-striatal circuit dysregulation
on choice behavior, thereby identifying factors that may exacerbate resistance to treatment. We will examine
synaptodendritic integrity in pyramidal neurons of the medial prefrontal cortex (mPFC) and medium spiny
neurons (MSN) of the nucleus accumbens given their sensitivity to drug history and/or HIV-1 infection.
Targeted proviral gene excision of HIV from microglial cells will be used to determine the role of infected
microglial cells in executive function deficits. Thus, this proposal addresses two key questions regarding
neuroHIV – 1) does a history of drug dependence alter the progression and clinical outcomes of HIV-1-
associated neurocognitive disorders? and 2) how do substances of abuse and HIV interact to produce dendritic
spine alterations, one of the key neuropathologies of neuroHIV in the current cART era? The program goal is
to identify how microglial HIV infections produce synaptodendritic loss; knowledge that will lead to novel
therapeutic strategies for restoring fronto-striatal circuitry.

## Key facts

- **NIH application ID:** 10850815
- **Project number:** 5R01DA059310-02
- **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
- **Principal Investigator:** Rosemarie M Booze
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $653,642
- **Award type:** 5
- **Project period:** 2023-06-01 → 2028-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10850815

## Citation

> US National Institutes of Health, RePORTER application 10850815, Microglial modulation of neurocircuits in HIV/cocaine comorbidity (5R01DA059310-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10850815. Licensed CC0.

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