# Neuroimaging Adaptive Microglia Processes During Extended Alcohol Drinking

> **NIH NIH R21** · YALE UNIVERSITY · 2023 · $334,811

## Abstract

PROJECT SUMMARY
 Acute alcohol triggers an immune response in the brain. A hallmark of this response is the activation of the
brain's primary immune cells, microglia. Microglia readily adapt to repeated stimuli, which can enhance or
attenuate microglia responses over time. However, preclinical findings characterizing these effects are highly
mixed depending on species, dose, alcohol chronicity, and timing. It is important to characterize adaptive
microglia processes during repeated alcohol exposures because innate neuroimmune factors are linked with
escalating alcohol drinking. Yet, these mechanisms cannot be evaluated yet in primates due to limited
noninvasive tools that measure microglia responses to acute immune challenges. This 2-phase proposal will
first develop a novel positron emission tomography (PET) radiotracer specific for the colony stimulating factor 1
receptor (CSF1R) that will characterize microglia dynamics from repeated alcohol exposures. CSF1R is
advantageous over current PET targets because it is expressed exclusively on microglia. This CSF1R PET
radiotracer will be evaluated for suitable imaging properties and sensitivity to an acute alcohol challenge.
Confirmation of these properties will provide a key tool for the second phase. Phase 2 will use this imaging tool
to measure the acute immune response to alcohol in nonhuman primates at three time points: alcohol naïve, a
week after initial alcohol challenge, and after 4 months alcohol self-administration. The data collected will
characterize adaptive microglia processes occur during alcohol initiation and escalating drinking, and
determine the relationship of these process with drinking behaviors. The findings will advance the field by
providing a new imaging tool ripe for translation to human studies while testing important hypotheses regarding
dynamic microglia processes from alcohol exposure and their effects on drinking behaviors. The results will
have clear translational implications for future human studies evaluating adaptive microglia processes in
people with alcohol use disorder and populations with high risk for future alcohol use disorder.

## Key facts

- **NIH application ID:** 10704077
- **Project number:** 5R21AA030380-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** YIYUN HENRY HUANG
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $334,811
- **Award type:** 5
- **Project period:** 2022-09-13 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10704077

## Citation

> US National Institutes of Health, RePORTER application 10704077, Neuroimaging Adaptive Microglia Processes During Extended Alcohol Drinking (5R21AA030380-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10704077. Licensed CC0.

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