# Mg-based therapy for mitigating HAND and neuropsychiatric symptoms in the condition of chronic HIV infection

> **NIH NIH R21** · OLD DOMINION UNIVERSITY · 2024 · $440,000

## Abstract

Abstract
Microglia (Mg), the brain residential macrophage, play critical roles in maintaining adult brain homeostasis. Mg
can function as multi-players such as housekeepers, guards, and warriors under both physiological and
pathological conditions. Accumulating evidence reveal that Mg also play vital roles in brain aging. Reversing or
eliminating senescent Mg and replenishing with new-born Mg have been suggested as treatment for aging and
neurodegenerative disease. Recently, Mg depletion and repopulation (MgDR) has been tested as a potential
therapeutic approach for acute brain injury and Alzheimer’s diseases. Mechanically, the repopulated Mg show
homeostatic phenotype with restoring BDNF signaling or increasing the activity of IL6 pathway to improve brain
functions. It has been well-accepted that sustained and lower levels of Mg activation promote Mg senescence
and contribute to HAND pathogenesis. Several anti-neuroinflammatory drugs have been proposed as alternative
approach for HAND therapy. However, whether MgDR could be a novel therapeutic approach to mitigate
neurological deficiency in chronic HIV (+) individuals have never been explored. We initiated pilot studies and
obtained these preliminary data: (1) Both HIV transgenic (Tg) rats and HIV-inducible (i) mice show increased
LDAM in the brains compared to age-matched counterparts; (2) HIV-iTAT mice show dysregulated lipid profile
in the brain hippocampus; (3) MgDR by PLX3397 restored locomotion coordination ability in HIV-iTAT male mice.
Based on these observations, we hypothesize that LDAM contribute to the pathogenesis of HAND and
neuropsychiatric symptoms and MgDR can exert therapeutic effects on brain dysfunctions in the context of
chronic HIV infection. The hypothesis will be tested in the following two specific aims (SA): SA1: Investigate the
effects of MgDR on HAND and neuropsychiatric symptoms in HIV-Tg26 mice. SA2: Explore the detailed
mechanisms underlying the effects of MgDR on brain pathology in vivo. This proposal will explore the therapeutic
effects of MgDR on brain pathology in the context of chronic HIV infection. If succeed, we could open a new
research direction to identify effective therapy to improve the life-quality of chronic HIV (+) individuals.

## Key facts

- **NIH application ID:** 11009095
- **Project number:** 1R21AG090171-01
- **Recipient organization:** OLD DOMINION UNIVERSITY
- **Principal Investigator:** Minglei Guo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $440,000
- **Award type:** 1
- **Project period:** 2024-09-20 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11009095

## Citation

> US National Institutes of Health, RePORTER application 11009095, Mg-based therapy for mitigating HAND and neuropsychiatric symptoms in the condition of chronic HIV infection (1R21AG090171-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11009095. Licensed CC0.

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