Evidence map›Paper›PMID 40204197›Full record

ArticleExperimental neurology2025

Daily acute intermittent hypoxia elicits age & sex-dependent changes in molecules regulating phrenic motor plasticity.

Jayakrishnan Nair, Alexandria B Marciante, Carter Lurk, Mia N Kelly, Capron Maclain, Gordon S Mitchell

Abstract read
In one paragraph

Article in Experimental neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Jayakrishnan NairBreathing Research and Therapeutics Center, Department of Physical Therapy, University of Florida, Gainesville, FL, USA; Department of Physical Therapy, Thomas Jefferson University, Philadelphia, PA, USA. Electronic address: jayakrishnan.nair@jefferson.edu.
Alexandria B MarcianteBreathing Research and Therapeutics Center, Department of Physical Therapy, University of Florida, Gainesville, FL, USA. Electronic address: amarciante@phhp.ufl.edu.
Carter LurkBreathing Research and Therapeutics Center, Department of Physical Therapy, University of Florida, Gainesville, FL, USA. Electronic address: carterlurk@tamu.edu.
Mia N KellyBreathing Research and Therapeutics Center, Department of Physical Therapy, University of Florida, Gainesville, FL, USA. Electronic address: miankelly@gmail.com.
Capron MaclainDepartment of Physical Therapy, Thomas Jefferson University, Philadelphia, PA, USA. Electronic address: maclain.capron@jefferson.edu.
Gordon S MitchellBreathing Research and Therapeutics Center, Department of Physical Therapy, University of Florida, Gainesville, FL, USA. Electronic address: gsmitche@phhp.ufl.edu.

Funding

Breathing Research and Therapeutics (BREATHE)T32HL134621 · NHLBI · UNIVERSITY OF FLORIDA · PI Gordon S. Mitchell · 2017 to 2026
$3.4M
Optimizing respiratory plasticity with chronic cervical SCIR01HL147554 · NHLBI · UNIVERSITY OF FLORIDA · PI MITCHELL, GORDON S. · 2019 to 2022
$2.9M
Regulation of Intermittent Hypoxia-Induced Respiratory Motor PlasticityR01HL148030 · NHLBI · UNIVERSITY OF FLORIDA · PI MITCHELL, GORDON S. · 2019 to 2022
$2.4M
NHLBI NIH HHS R01 HL147554NHLBI NIH HHS R01 HL148030NHLBI NIH HHS T32 HL134621
6 · The paper itself

Abstract

Acute intermittent hypoxia (AIH) elicits a form of respiratory motor plasticity known as phrenic long-term facilitation (pLTF). Exposure to repetitive daily AIH (dAIH) enhances pLTF, a form of metaplasticity. Little is known concerning cellular mechanisms giving rise to dAIH-induced metaplasticity and the age-dependent sexual dimorphism of AIH associated pro-plasticity mRNA expression. To test if age, sex, and dAIH effects are associated with differential expression of molecules that regulate the Q- and S-pathways and their cross-talk interactions to phrenic motor facilitation, we analyzed key regulatory molecules in ventral spinal (C3-C5) homogenates from young (3-month) and middle-aged (12-month) male and female Sprague-Dawley rats. Since CNS estrogen levels impact molecules known to regulate the Q- and S-pathways, mRNA was correlated with serum estradiol. Rats (n = 8/group) were exposed to sham (21 % O2) or dAIH (15, 1 min episodes of 10.5 % inspired O2) per day for 14 days and sacrificed 24 h later. mRNAs for pLTF regulating molecules were assessed via RT-PCR, including: brain-derived neurotrophic factor (Bdnf); serotonin 2 A (Htr2a), 2B (Htr2b), and 7 (Htr7) receptors; adenosine 2a (Adora2a) receptors; exchange protein activated by cAMP (Epac1); p38 MAP kinase [Mapk14 (α) & Mapk11 (β)]; PKA regulatory (Prkar1a) and; catalytic subunits (Prkaa1); fractalkine (Cx3cl1), which underlies motor neuron/microglia communication; phosphodiesterase type 4b (Pde4b); NAPDH- gp91 (Cybb) and p47 (ncf1); and the PKC isoform, PKCδ (Prkcd). Here we report that age, sex, dAIH preconditioning, and estradiol influence molecules that initiate and/or regulate the Q- and S-pathways to phrenic motor facilitation.

Indexed as

AgingHypoxiaNeuronal PlasticityPhrenic NerveSex CharacteristicsAnimalsFemaleMaleRatsRats, Sprague-DawleyAcute intermittent hypoxiaAgeEstradiolGene expressionPhrenic long-term facilitationPlasticitySex difference

Identifiers

PMID40204197
PMCPMC12839288

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.