# Epigenetic mechanisms underlying cannabinoid modulation of neuroinflammation in HIV/SIV infection-supplement

> **NIH NIH R01** · TEXAS BIOMEDICAL RESEARCH INSTITUTE · 2022 · $472,498

## Abstract

ABSTRACT
Alzheimer’s disease (AD) and related dementias lead to massive costs and human suffering in the United
States and worldwide and the number of people affected by these diseases is expected to increase as the
global population age increases. Although aging is the greatest known risk factor for the development of
neurodegenerative diseases like AD, concurrent HIV infection and ensuing oxidative stress and chronic
inflammation may potentially facilitate the development of AD. Chronic neuroinflammation characterized by
persistent activation brain microglia is considered a central mechanism in AD and may potentiate its
pathogenesis. Our preliminary studies identified significant upregulation of oxidative stress and
proinflammatory interferon stimulated and chemokine genes in basal ganglia of chronically SIV-infected
macaques. More importantly, chronic cannabinoid treatment to ART naïve SIV-infected rhesus macaques
suppressed proinflammatory gene expression in BG, and more importantly, significantly increased plasma
concentrations of indole-3-propionate, a gut microbe derived indole metabolite with potent ability to suppress
oxidative stress, neuroinflammation and inhibit amyloid-beta fibril formation given as a supplement (OXIGON
®) to AD patients suggesting their immense therapeutic potential for attenuating neuroinflammation and
neurocognitive decline in AD patients. In rodent models of AD, cannabinoids reduced neuroinflammation and
stimulated neurogenesis in the hippocampus. To obtain a deeper understanding of the mechanisms
associated with anti-inflammatory and neurogenic potential of cannabinoids, we will utilize spatial
transcriptomics to analyze gene expression changes in cells in their morphological context to unravel the
pathological changes caused by amyloid plaques on adjacent cells like astrocytes, neurons, microglia, etc. in
the brain Further, we will determine the effect of combination anti-retroviral treatment (cART) in conjunction
with chronic cannabinoid treatments longitudinally on neurocognitive function, levels of proinflammatory
cytokine and other markers in blood and cerebrospinal fluid and microglial activation using PET/CT imaging.
The proposed research is highly innovative and applies state of the art immunological, imaging and molecular
approaches to fill a significant gap in our understanding of the proinflammatory mechanisms associated with
AD and HAND and its modulation by safe disease modifying interventions like low dose cannabinoids.

## Key facts

- **NIH application ID:** 10499891
- **Project number:** 3R01DA052845-03S1
- **Recipient organization:** TEXAS BIOMEDICAL RESEARCH INSTITUTE
- **Principal Investigator:** Siddappa N Byrareddy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $472,498
- **Award type:** 3
- **Project period:** 2020-09-30 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499891

## Citation

> US National Institutes of Health, RePORTER application 10499891, Epigenetic mechanisms underlying cannabinoid modulation of neuroinflammation in HIV/SIV infection-supplement (3R01DA052845-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10499891. Licensed CC0.

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