ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
Spinal adenosine A2a receptor activation elicits long-lasting phrenic motor facilitation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 1 of them a synthesis that pooled it.
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Who cites it
105 citing papers in PubMed, 1 synthesis or guideline pooled it, 160 citations in OpenAlex.
- Quantitative assessment of integrated phrenic nerve activity.Respiratory physiology & neurobiology · 2016Pooled it
- Acute intermittent hypoxia and respiratory muscle recruitment in people with amyotrophic lateral sclerosis: A preliminary study.Experimental neurology · 2022Trial
- Pairing ampakine with brief hypoxia evokes phrenic neuroplasticity via a spinal NMDA receptor-mediated mechanism.Function (Oxford, England) · 2026Article
- Vagal suppression of diurnal variations in acute intermittent hypoxia-induced phrenic long-term facilitation.Journal of neurophysiology · 2026Article
- Persistent suppression of phrenic motor plasticity after mild acute systemic inflammation in adult rats.Function (Oxford, England) · 2026Article
- Sexual dimorphisms in phrenic long-term facilitation following severe acute intermittent hypoxia.Journal of neurophysiology · 2026Article
- Acute Adenosine Receptor Antagonism in Combination With Acute Intermittent Hypoxia to Promote Breathing Plasticity in Amyotrophic Lateral Sclerosis: Protocol for a Randomized, Double-Blinded, Placebo-Controlled Trial.JMIR research protocols · 2025Article
- Plasticity induced loss of apnea alarm through repeated apneas: A proposed mechanism for respiratory sudden death.Epilepsy & behavior : E&B · 2025Review
- Phrenic long-term facilitation following severe acute intermittent hypoxia is preserved in geriatric male rats.Journal of neurophysiology · 2025Article
- Daily acute intermittent hypoxia elicits age & sex-dependent changes in molecules regulating phrenic motor plasticity.Experimental neurology · 2025Article
- Identification of multiple hypoxia-independent triggers of upper airway long-term facilitation in a rat model of upper airway motor plasticity.Physiological reports · 2025Article
- A case report of long-latency evoked diaphragm potentials after exposure to acute intermittent hypoxia in post-West Nile virus meningoencephalitis.Journal of neurophysiology · 2025Article
- Microglia regulate motor neuron plasticity via reciprocal fractalkine and adenosine signaling.Nature communications · 2024Article
- Inactivity-induced phrenic motor facilitation requires PKCζ activity within phrenic motor neurons.Journal of neurophysiology · 2024Article
- Microglia regulate motor neuron plasticity via reciprocal fractalkine/adenosine signaling.bioRxiv : the preprint server for biology · 2024Article
- Spinal TNF-α receptor 1 is differentially required for phrenic long-term facilitation (pLTF) over the course of motor neuron death in adult rats.Frontiers in physiology · 2024Article
- Increased spinal adenosine impairs phrenic long-term facilitation in aging rats.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Article
- Targeting drug or gene delivery to the phrenic motoneuron pool.Journal of neurophysiology · 2023Review
- Magnitude and Mechanism of Phrenic Long-term Facilitation Shift Between Daily Rest Versus Active Phase.Function (Oxford, England) · 2023Article
- Systemic Administration of Tempol, a Superoxide Dismutase Mimetic, Augments Upper Airway Muscle Activity in Obese Zucker Rats.Frontiers in pharmacology · 2022Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Acute intermittent hypoxia elicits a form of spinal, brain-derived neurotrophic factor (BDNF)-dependent respiratory plasticity known as phrenic long-term facilitation. Ligands that activate G(s)-protein-coupled receptors, such as the adenosine 2a receptor, mimic the effects of neurotrophins in vitro by transactivating their high-affinity receptor tyrosine kinases, the Trk receptors. Thus, we hypothesized that A2a receptor agonists would elicit phrenic long-term facilitation by mimicking the effects of BDNF on TrkB receptors. Here we demonstrate that spinal A2a receptor agonists transactivate TrkB receptors in the rat cervical spinal cord near phrenic motoneurons, thus inducing long-lasting (hours) phrenic motor facilitation. A2a receptor activation increased phosphorylation and new synthesis of an immature TrkB protein, induced TrkB signaling through Akt, and strengthened synaptic pathways to phrenic motoneurons. RNA interference targeting TrkB mRNA demonstrated that new TrkB protein synthesis is necessary for A2a-induced phrenic motor facilitation. A2a receptor activation also increased breathing in unanesthetized rats, and improved breathing in rats with cervical spinal injuries. Thus, small, highly permeable drugs (such as adenosine receptor agonists) that transactivate TrkB receptors may provide an effective therapeutic strategy in the treatment of patients with ventilatory control disorders, such as obstructive sleep apnea, or respiratory insufficiency after spinal injury or during neurodegenerative diseases.
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Registered trials
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.