ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Cervical spinal erythropoietin induces phrenic motor facilitation via extracellular signal-regulated protein kinase and Akt signaling.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 52 citations in OpenAlex.
- Sexual dimorphisms in phrenic long-term facilitation following severe acute intermittent hypoxia.Journal of neurophysiology · 2026Article
- Feasibility of transcranial magnetic stimulation adjuvant therapy for chronic respiratory diseases: a narrative review.Frontiers in rehabilitation sciences · 2026Review
- BDNF-induced phrenic motor facilitation shifts from PKCθ to ERK dependence with mild systemic inflammation.Journal of neurophysiology · 2023Article
- Novel role for non-invasive neuromodulation techniques in central respiratory dysfunction.Frontiers in neuroscience · 2023Review
- The phrenic neuromuscular system.Handbook of clinical neurology · 2022Review
- Electrical epidural stimulation of the cervical spinal cord: implications for spinal respiratory neuroplasticity after spinal cord injury.Journal of neurophysiology · 2021Review
- The Role of PI3K/AKT and MAPK Signaling Pathways in Erythropoietin Signalization.International journal of molecular sciences · 2021Review
- Erythropoietin as candidate for supportive treatment of severe COVID-19.Molecular medicine (Cambridge, Mass.) · 2020Review
- Impact of inflammation on developing respiratory control networks: rhythm generation, chemoreception and plasticity.Respiratory physiology & neurobiology · 2020Review
- Adenosine 2A receptor inhibition protects phrenic motor neurons from cell death induced by protein synthesis inhibition.Experimental neurology · 2020Article
- Mechanisms of compensatory plasticity for respiratory motor neuron death.Respiratory physiology & neurobiology · 2019Review
- Intranasal erythropoietin ameliorates neurological function impairments and neural pathology in mice with chronic alcoholism by regulating autophagy‑related Nrf2 degradation.Molecular medicine reports · 2019Article
- Spinal protein phosphatase 1 constrains respiratory plasticity after sustained hypoxia.Journal of applied physiology (Bethesda, Md. : 1985) · 2018Article
- Spinal activation of protein kinase C elicits phrenic motor facilitation.Respiratory physiology & neurobiology · 2018Article
- Cyclooxygenase enzyme activity does not impair respiratory motor plasticity after one night of intermittent hypoxia.Respiratory physiology & neurobiology · 2018Article
- Enhancement of phrenic long-term facilitation following repetitive acute intermittent hypoxia is blocked by the glycolytic inhibitor 2-deoxyglucose.American journal of physiology. Regulatory, integrative and comparative physiology · 2018Article
- Article
- Spinal BDNF-induced phrenic motor facilitation requires PKCθ activity.Journal of neurophysiology · 2017Article
- Mechanisms of Enhanced Phrenic Long-Term Facilitation inThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis.Comprehensive Physiology · 2016Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Erythropoietin (EPO) is typically known for its role in erythropoiesis but is also a potent neurotrophic/neuroprotective factor for spinal motor neurons. Another trophic factor regulated by hypoxia-inducible factor-1, vascular endothelial growth factor (VEGF), signals via ERK and Akt activation to elicit long-lasting phrenic motor facilitation (pMF). Because EPO also signals via ERK and Akt activation, we tested the hypothesis that EPO elicits similar pMF. Using retrograde labeling and immunohistochemical techniques, we demonstrate in adult, male, Sprague Dawley rats that EPO and its receptor, EPO-R, are expressed in identified phrenic motor neurons. Intrathecal EPO at C4 elicits long-lasting pMF; integrated phrenic nerve burst amplitude increased >90 min after injection (63 ± 12% baseline 90 min after injection; p < 0.001). EPO increased phosphorylation (and presumed activation) of ERK (1.6-fold vs controls; p < 0.05) in phrenic motor neurons; EPO also increased pAkt (1.6-fold vs controls; p < 0.05). EPO-induced pMF was abolished by the MEK/ERK inhibitor U0126 [1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto)butadiene] and the phosphatidylinositol 3-kinase/Akt inhibitor LY294002 [2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one], demonstrating that ERK MAP kinases and Akt are both required for EPO-induced pMF. Pretreatment with U0126 and LY294002 decreased both pERK and pAkt in phrenic motor neurons (p < 0.05), indicating a complex interaction between these kinases. We conclude that EPO elicits spinal plasticity in respiratory motor control. Because EPO expression is hypoxia sensitive, it may play a role in respiratory plasticity in conditions of prolonged or recurrent low oxygen.
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