One bout of neonatal inflammation impairs adult respiratory motor plasticity in male and female rats

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Abstract

Neonatal inflammation is common and has lasting consequences for adult health. We investigated the lasting effects of a single bout of neonatal inflammation on adult respiratory control in the form of respiratory motor plasticity induced by acute intermittent hypoxia, which likely compensates and stabilizes breathing during injury or disease and has significant therapeutic potential. Lipopolysaccharide-induced inflammation at postnatal day four induced lasting impairments in two distinct pathways to adult respiratory plasticity in male and female rats. Despite a lack of adult pro-inflammatory gene expression or alterations in glial morphology, one mechanistic pathway to plasticity was restored by acute, adult anti-inflammatory treatment, suggesting ongoing inflammatory signaling after neonatal inflammation. An alternative pathway to plasticity was not restored by anti-inflammatory treatment, but was evoked by exogenous adenosine receptor agonism, suggesting upstream impairment, likely astrocytic-dependent. Thus, the respiratory control network is vulnerable to early-life inflammation, limiting respiratory compensation to adult disease or injury.

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All data generated or analyzed during this study are included in the manuscript and supporting files. Source data are available for all figures.

Article and author information

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Austin D Hocker

Department of Human Physiology, University of Oregon, Eugene, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-2941-2581
Sarah A Beyeler

Department of Human Physiology, University of Oregon, Eugene, United States

Competing interests
The authors declare that no competing interests exist.
Alyssa N Gardner

Department of Comparative Biosciences, University of Wisconsin, Madison, United States

Competing interests
The authors declare that no competing interests exist.
Stephen M Johnson

Department of Comparative Biosciences, University of Wisconsin, Madison, United States

Competing interests
The authors declare that no competing interests exist.
Jyoti J Watters

Department of Comparative Biosciences, University of Wisconsin, Madison, United States

Competing interests
The authors declare that no competing interests exist.
Adrianne G Huxtable

Department of Human Physiology, University of Oregon, Eugene, United States

For correspondence
huxtable@uoregon.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-8745-2231

Funding

National Institutes of Health (HL141249)

Adrianne G Huxtable

National Institutes of Health (HL111598)

Jyoti J Watters

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee protocols (#18-02) of the University of Oregon. All surgeries were performed under isoflurane or urethane anesthesia and every effort was made to minimize pain, distress, or discomfort.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.