# Project 3:  Role of Microglial α7nAChR in Diet Induced Brain Inflammation

> **NIH NIH P20** · UNIVERSITY OF PUERTO RICO MED SCIENCES · 2021 · $205,120

## Abstract

The α7 nAChRs has emerged as a potential target in the treatment of many neurodegenerative disorders,
which have been found to be associated with an inflammatory response. The α7 nAChRs are expressed in
macrophages where they play a key role in the cholinergic anti-inflammatory pathway, were they have
proven to be an effective target in the treatment of sepsis, myocardial ischemia, and rheumatoid arthritis.
However little is known about the role that α7 nAChRs play on brain inflammation. Interestingly, it has
been shown that a high fat diet on wild-type mice causes the activation of microglia resulting in
impairments on working memory and in humans an elevated serum cholesterol is a risk factor for mild
cognitive impairment and dementia. Suggesting that dietary fat content affects the function of the brain.
Using electrophysiology and pharmacological manipulation of lipids, we demonstrated that changes in
lipid levels in the plasma membrane causes dramatic changes in the function of the α7 nAChRs. To dissect
the role that α7 nAChR plays on the high fat diet mediated microglia activation and subsequent
development of neuroinflammation, we will generate microglia specific α7 nAChR knockout mice and
compare them with control, fed either a normal or high fat diet. We will look at the activation of
inflammatory responses over time, the function of neuronal α7 nAChRs, and the susceptibility of neuronal
cell death caused by dietary induced changes in inflammatory response. The results will help us discern
the role of α7nAChR in both microglia activation and subsequent neuronal cell death, and shed light in
the possibility of targeting α7 nAChRs therapeutically in the prevention of obesity induced dementia.

## Key facts

- **NIH application ID:** 10212405
- **Project number:** 5P20GM103642-09
- **Recipient organization:** UNIVERSITY OF PUERTO RICO MED SCIENCES
- **Principal Investigator:** Jose Orlando Colon-Saez
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $205,120
- **Award type:** 5
- **Project period:** 2013-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212405

## Citation

> US National Institutes of Health, RePORTER application 10212405, Project 3:  Role of Microglial α7nAChR in Diet Induced Brain Inflammation (5P20GM103642-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10212405. Licensed CC0.

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