# Impact of miRNAs on adult neurogenesis following exposure to methamphetamine and HIV-1 Infection

> **NIH NIH R21** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2024 · $191,875

## Abstract

ABSTRACT
In the United States, it is estimated that more than 9% of people living with HIV acquired the virus through
injection of substances or substance abuse-related sexual contact. Although substance use is well known
to exacerbate HIV-associated neurotoxicity, there is no prompt treatment for alleviating neurocognitive
dysfunctions in HIV-positive individuals. Our proposal is based on significant discoveries regarding the
impact of chronic METH and HIV on the neurogenic niche, such as (i) HIV can infect the neural progenitor
cells (NPCs) in subventricular zone (SVZ) of the lateral ventricle in mouse brain; (ii) chronic METH and HIV
changes microRNA (miRNA) profiles of ex vivo NPCs; and (iii) METH and HIV-disrupted blood-brain barrier
(BBB) integrity increases brain inflammation, but it does not stimulate the migration of NPCs in that lesion.
The overall goal of this proposal is to investigate a novel mechanism linking the BBB pericytes and NPCs
in chronic METH and HIV-induced alterations of NPC migration mediated by miRNAs. In order to evaluate
this hypothesis, our transdisciplinary study will focus on the role of miR-21-5p, whose expression is
significantly reduced in METH and HIV-exposed mouse SVZ NPCs and plasma samples, in the alteration of
SVZ NPCs migration (Aim 1), and the crosstalk between the BBB pericytes and NPCs in response to METH
exposure and HIV infection in the brain (Aim 2). We anticipate that this proposed research will
demonstrate the potential of restoring the NPC migration to combat the neurotoxic effects of METH and
HIV, ultimately improving neurocognitive function by enhancing adult neurogenesis.
The focus on the interaction between the brain microvasculature and NPC migration, which influences
the development of neurocognitive dysfunctions following chronic METH exposure and HIV infection, is
an innovative and cutting-edge conceptual approach. Moreover, given the growing evidence linking
miRNA expression alterations to substance abuse and HIV infection, studying the role of miRNAs in METH
and HIV-induced altered neurogenesis is crucial and provide new insights into the underlying mechanisms
of neurotoxicity and potential therapeutic targets.

## Key facts

- **NIH application ID:** 10838831
- **Project number:** 1R21DA060085-01
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** MIN SEON PARK
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $191,875
- **Award type:** 1
- **Project period:** 2024-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10838831

## Citation

> US National Institutes of Health, RePORTER application 10838831, Impact of miRNAs on adult neurogenesis following exposure to methamphetamine and HIV-1 Infection (1R21DA060085-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10838831. Licensed CC0.

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