Prolonged intermittent hypoxia differentially regulates phrenic motor neuron serotonin receptor expression in rats following chronic cervical spinal cord injury.

Autor: Gonzalez-Rothi EJ; Breathing Research and Therapeutics Center, Department of Physical Therapy & McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA. Electronic address: elisagon@phhp.ufl.edu., Allen LL; Breathing Research and Therapeutics Center, Department of Physical Therapy & McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA., Seven YB; Breathing Research and Therapeutics Center, Department of Physical Therapy & McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA., Ciesla MC; Breathing Research and Therapeutics Center, Department of Physical Therapy & McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA., Holland AE; Breathing Research and Therapeutics Center, Department of Physical Therapy & McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA., Santiago JV; Breathing Research and Therapeutics Center, Department of Physical Therapy & McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA., Mitchell GS; Breathing Research and Therapeutics Center, Department of Physical Therapy & McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA.
Jazyk: angličtina
Zdroj: Experimental neurology [Exp Neurol] 2024 Aug; Vol. 378, pp. 114808. Date of Electronic Publication: 2024 May 14.
DOI: 10.1016/j.expneurol.2024.114808
Abstrakt: Low-dose (< 2 h/day), acute intermittent hypoxia (AIH) elicits multiple forms of serotonin-dependent phrenic motor plasticity and is emerging as a promising therapeutic strategy to restore respiratory and non-respiratory motor function after spinal cord injury (SCI). In contrast, high-dose (> 8 h/day), chronic intermittent hypoxia (CIH) undermines some forms of serotonin-dependent phrenic motor plasticity and elicits pathology. CIH is a hallmark of sleep disordered breathing, which is highly prevalent in individuals with cervical SCI. Interestingly, AIH and CIH preconditioning differentially impact phrenic motor plasticity. Although mechanisms of AIH-induced plasticity in the phrenic motor system are well-described in naïve rats, we know little concerning how these mechanisms are affected by chronic SCI or intermittent hypoxia preconditioning. Thus, in a rat model of chronic, incomplete cervical SCI (lateral spinal hemisection at C2 (C2Hx), we assessed serotonin type 2A, 2B and 7 receptor expression in and near phrenic motor neurons and compared: 1) intact vs. chronically injured rats; and 2) the impact of preconditioning with varied "doses" of intermittent hypoxia (IH). While there were no effects of chronic injury or intermittent hypoxia alone, CIH affected multiple receptors in rats with chronic C2Hx. Specifically, CIH preconditioning (8 h/day; 28 days) increased serotonin 2A and 7 receptor expression exclusively in rats with chronic C2Hx. Understanding the complex, context-specific interactions between chronic SCI and CIH and how this ultimately impacts phrenic motor plasticity is important as we leverage AIH-induced motor plasticity to restore breathing and other non-respiratory motor functions in people with chronic SCI.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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