Front. Physiol.

Sec. Respiratory Physiology and Pathophysiology

Volume 15 - 2024 | doi: 10.3389/fphys.2024.1488951

This article is part of the Research Topic Respiratory Dysfunction in Neurological Disease and Injury: Novel Mechanisms and Potential Therapeutics View all 6 articles

Provisionally accepted

Ryan D Lewis 1 Amy Keilholz 2 Catherine L Smith 2 Ethan A Burd 3 Nicole L. Nichols 2* 1 Grinnell College, Grinnell, Iowa, United States 2 University of Missouri, Columbia, United States 3 Seton Hill University, Greensburg, Pennsylvania, United States

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Introduction: Intrapleural injections of cholera toxin B conjugated to saporin (CTB-SAP) result in selective respiratory (e.g., phrenic) motor neuron death and mimics aspects of motor neuron disease [(e.g., amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA)], such as breathing deficits. This rodent model allows us to study the impact motor neuron death has on the output of surviving phrenic motor neurons as well as the compensatory mechanisms that are recruited. Microglial density in the phrenic motor nucleus as well as cervical gene expression of markers associated with inflammation (e.g., tumor necrosis factor ; TNF-) are increased following CTB-SAP-induced phrenic motor neuron death, and ketoprofen (nonsteroidal anti-inflammatory drug) delivery attenuated phrenic long-term facilitation (pLTF) in 7 day (d) CTB-SAP rats but enhanced pLTF in 28d CTB-SAP rats. Methods: Here, we worked to determine the impact of TNF- in the phrenic motor nucleus by: 1) quantifying TNFR1 (a high affinity transmembrane receptor for TNF-) expression; 2) investigating astrocytes (glial cells known to release TNF-) by performing a morphological analysis in the phrenic motor nucleus; and 3) determining whether acute TNFR1 inhibition differentially affects phrenic plasticity over the course of CTB-SAP-induced motor neuron loss by delivering an inhibitor for TNF- receptor 1 (sTNFR1i) in 7d and 28d male CTB-SAP and control rats. Results: Results revealed that TNFR1 expression was increased on phrenic motor neurons of 28d CTB-SAP rats (p

Keywords: Phrenic motor neuron death, breathing, Respiration, plasticity, astrocyte, rat model

Received: 31 Aug 2024; Accepted: 18 Nov 2024.

Copyright: © 2024 Lewis, Keilholz, Smith, Burd and Nichols. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Nicole L. Nichols, University of Missouri, Columbia, United States

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