# Peripheral BDZ Receptor - Biomarker of Neurotoxicity

> **NIH NIH R01** · FLORIDA INTERNATIONAL UNIVERSITY · 2021 · $462,604

## Abstract

Project Summary (Abstract): The long-term goal of this research is to understand the function(s) of
Translocator Protein 18 kDa (TSPO) in glial cells, specifically in microglia. TSPO is a glial stress response
protein that we have previously validated as a biomarker of brain injury and inflammation and it is currently
used in preclinical and clinical Positron Emission Tomography (PET) imaging studies throughout the world.
TSPO is a sensitive biomarker that is able to detect brain injury and neuroinflammation in a number of human
neurodegenerative and mental conditions as well as in neurodegeneration induced by exposures to
environmental chemicals. Furthermore, we are currently using TSPO as a biomarker of neurotoxicity to screen
the neurotoxicity of chemicals for which there is currently no information on their potential to damage the brain.
Despite the widespread use of TSPO in clinical and preclinical studies, there is a paucity of knowledge on the
function(s) of TSPO in glial cells (microglia and astrocytes), the cell types that upregulate TSPO under
neuropathological conditions. This proposal is aimed at understanding a novel interaction that we have
discovered between TSPO and NADPH Oxidase (NOX2) in microglia that may provide important insights on
modulation of brain reactive oxygen species (ROS) production and neuroinflammation. We present rigorously
performed studies demonstrating the TSPO-NOX2 interaction and its modulation by microglia activation. There
are three specific aims in the proposed research. Specific aim 1 will examine the function of TSPO in primary
microglia generated from wildtype and global TSPO knockout (TSPO-gKO) as well as microglia-specific
conditional TSPO (mTSPO-cKO) mice. Specific aim 2 will examine the subcellular localization and functional
significance of the TSPO-NOX2 interaction in microglia. Finally, specific aim 3 will examine the neurological
effects of TSPO deletion (global and microglia-specific) at the whole animal level. Combined, the proposed
studies will generate new information on the function of TSPO in microglia. We will use state-of-the-art
molecular and cellular techniques to understand the function of TSPO in microglia. A precise understanding of
this novel TSPO-NOX2 interaction will provide new insights for devising therapeutics strategies for
neurodegenerative conditions that involve neuroinflammation since NOX2 is involved in microglia-mediated
neurodegeneration. This research topic is consistent with strategic objective 1 in advancing environmental
health sciences basic biological research which is an integral part of the National Institute of Environmental
Health Sciences strategic plan 2018-2023: Advancing Environmental Health Science, Improving Health 2.0.

## Key facts

- **NIH application ID:** 10176485
- **Project number:** 5R01ES007062-22
- **Recipient organization:** FLORIDA INTERNATIONAL UNIVERSITY
- **Principal Investigator:** Tomas R Guilarte
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $462,604
- **Award type:** 5
- **Project period:** 2019-09-19 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176485

## Citation

> US National Institutes of Health, RePORTER application 10176485, Peripheral BDZ Receptor - Biomarker of Neurotoxicity (5R01ES007062-22). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10176485. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*