# HIV/COCAINE NEUROTOXICITY IN FEMALES

> **NIH NIH R01** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 2021 · $578,365

## Abstract

Project Summary:
In this competing renewal application, we will critically test a gene excision cure approach followed by
neurorestoration therapy as a strategy to remove the HIV-1 provirus from the brain and promote neurocognitive
recovery. Furthermore, efficacy of cure/restoration may be tailored for both males and females, as well as for
those with a history of cocaine abuse. The hypothesis is that gene excision and estrogen/soy isoflavone
therapy will restore neurocognitive function and synaptic complexity from the progressive decline characteristic
of HIV-1 associated neurocognitive disorders (HAND). Thus, estrogenic compounds may serve as
neurorestorative agents for the combined effects of cocaine/HIV proteins on producing synaptic impairments in
the nucleus accumbens and prefrontal cortex, critical brain regions involved in the cognitive dysfunction
associated with HAND. The specific aims are: 1) To establish efficacious neurorestoration of HIV-1/
cocaine-induced synaptopathy. The proposed in vitro experiments will establish neurorestoration at the
synaptic level following both provirus activation and HIV-1 gene excision strategies. Novel compounds will be
examined for neurorestoration of HIV-1 protein induced synaptopathy following cure strategies, with and
without cocaine co-exposures, in sex-specified cell cultures. 2) To establish recovery from executive
function deficits in HIV-1 transgenic animals, and the role of biological sex, with gene excision/
neurorestorative therapies. The ability to restore the neurocognitive/pathological consequences of HIV-1
proteins will be determined using assessment of executive function and synaptic plasticity/dendritic spines.
Investigations will focus on quantifying spine density changes with respect to regulators of nucleus accumbens
medium spiny neurons and prefrontal cortical neuronal plasticity. 3) To establish neurocognitive recovery in
HIV-1 Tg animals, with deficits exacerbated by a history of cocaine abuse, with gene excision/
neurorestoration therapies. A critical in vivo test of gene excision/neurorestoration therapies will be provided
with HIV-1 Tg animals that have an acquired history of cocaine self-administration; cocaine may accelerate the
progression of HAND in HIV-1 infected patients by disrupting frontal cortex-nucleus accumbens circuitry. The
robustness and generality of neurorestoration will subsequently be tested with self-administration of other
abused substances (e.g. methamphetamine and methylphenidate). We are in a unique position to establish the
trajectory of neurocognitive decline and synaptodendritic loss consequent to chronic HIV-1 protein/provirus
expression and critically test a gene excision/regenerative-based therapeutic approach to protect and/or
restore synaptodendritic complexity and neurocognitive function.

## Key facts

- **NIH application ID:** 10110002
- **Project number:** 5R01DA013137-20
- **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:** 2021
- **Award amount:** $578,365
- **Award type:** 5
- **Project period:** 2000-04-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10110002

## Citation

> US National Institutes of Health, RePORTER application 10110002, HIV/COCAINE NEUROTOXICITY IN FEMALES (5R01DA013137-20). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10110002. Licensed CC0.

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