# Neural and Molecular Mechanisms Underlying Stress-Induced Inflammatory Responses

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $621,869

## Abstract

PROJECT SUMMARY/ABSTRACT
Cardiovascular disease (CVD) is the number one killer of Americans, and also causes significant economic costs
to the nation. Thus, understanding the mechanisms through which CVD develops is of paramount importance if
we are to successfully identify those at risk for CVD, and intervene to ultimately prevent CVD-related death and
economic impact. Psychological stress reactivity has long been appreciated as a risk factor for negative CVD-
related outcomes, and recent work suggests that inflammatory reactivity to stress is a critical biological
mechanism through which stress increases risk for CVD. However, there are significant gaps in our current
knowledge regarding the neural predictors and molecular pathways through which stress leads to inflammation.
These knowledge gaps are critical to fill if we are to develop a full mechanistic understanding of how stress leads
to CVD risk, and may also shed light on future intervention targets. Thus, the present project will use cutting-
edge computational methods to identify neural signatures of stress-related inflammatory reactivity, and will use
pharmacological tools to block an important stress-signaling pathway (i.e., beta-adrenergic signaling) and
examine its effects on neural and inflammatory reactivity to stress. Study 1 (N=100) will use fMRI to examine
neural responses to a social evaluative stress task, with blood samples taken before and after the stressor
assayed for pro-inflammatory gene expression and circulating inflammatory proteins. We will use innovative
multivariate machine learning analytic techniques to identify the neural patterns that predict changes in
inflammation, as well as network-based analytic tools from mathematics to examine how large-scale brain
networks change configuration in response to stress in ways that are linked to inflammation. In Study 2 (N=120),
we will conduct a mechanistic, randomized, double-blind, placebo-controlled trial of the beta-adrenergic receptor
blocker propranolol to examine how blocking beta-adrenergic signaling impacts neural and inflammatory
responses to the social evaluative stress task. Together, these two studies will allow us to establish the neural
signatures of stress-induced increases in inflammation (Aim 1), determine the effects of beta-adrenergic
signaling on neural responses to stress (Aim 2), and examine the neural mediators of beta-adrenergic related
attenuations in stress-related inflammatory reactivity (Aim 3). In doing so, this project will ultimately help identify
neural signatures of risk for stress-related inflammation, as well as novel targets for future intervention to
ameliorate the impact of stress on the brain and body and reduce the health and economic burden of CVD.

## Key facts

- **NIH application ID:** 10185562
- **Project number:** 1R01HL157422-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Keely Ann Muscatell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $621,869
- **Award type:** 1
- **Project period:** 2021-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10185562

## Citation

> US National Institutes of Health, RePORTER application 10185562, Neural and Molecular Mechanisms Underlying Stress-Induced Inflammatory Responses (1R01HL157422-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10185562. Licensed CC0.

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