# Sympathetic regulation of inflammation from sleep fragmentation

> **NIH NIH R15** · WESTERN KENTUCKY UNIVERSITY · 2021 · $429,768

## Abstract

Project Summary
Primary sleep abnormalities (insomnia, shift work, and obstructive sleep apnea) promote an inflammatory
environment and are associated with the development of cardiovascular and metabolic disease. However, the
mechanisms underlying these relationships are poorly understood. The proposed research examines hormonal
mechanisms that underlie the inflammatory response to sleep fragmentation (SF) using pharmacological
approaches in mice. Previous R15-funded research in our lab examined the effect of sympathetic nervous
system (SNS) activation upon inflammatory responses to sleep loss. In this renewal application, the role that
activation of the hypothalamic-pituitary-adrenal (HPA) axis plays in modulating inflammation from acute and
chronic SF will be investigated. Aim 1 will examine whether glucocorticoids mediate the onset of SF-induced
inflammation and the activation of microglia, an important contributor to neuroinflammation. Specifically, mice
will be adrenalectomized, sham-adrenalectomized, or adrenalectomized and rescued with exogenous
glucocorticoids and then subjected to acute and chronic SF. Pro- and antiinflammatory gene and protein
expression will be assessed using RT-PCR and multiplex Luminex protein arrays, respectively.
Immunocytochemistry will be used to assess microglia activation. These findings will be validated through
pharmacological inhibition of glucocorticoid production and binding to glucocorticoid receptors. Instead of a
classic anti-inflammatory effect, it is predicted that glucocorticoids will prime SF-induced inflammation. Aim 2
will examine the time course of glucocorticoid release and pro-inflammatory responses to acute and chronic
SF. Taken together, the proposed research will assess the importance of the adrenocortical response in
mediating inflammation during sleep loss, and provide unique training opportunities for undergraduates
interested in conducting biomedical research in endocrinology, immunology, and the neurosciences.

## Key facts

- **NIH application ID:** 10201814
- **Project number:** 2R15GM117534-02
- **Recipient organization:** WESTERN KENTUCKY UNIVERSITY
- **Principal Investigator:** Noah Todd Ashley
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $429,768
- **Award type:** 2
- **Project period:** 2016-09-21 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201814

## Citation

> US National Institutes of Health, RePORTER application 10201814, Sympathetic regulation of inflammation from sleep fragmentation (2R15GM117534-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10201814. Licensed CC0.

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