Role of neurotrophic signaling pathways in regulating respiratory motor plasticity.
The respiratory neural network is flexible and can undergo neuronal plasticity. Recent work suggests that neurotrophins and their high-affinity tyrosine kinase (Trk) receptors are involved in mediating plasticity of respiratory motor output elicited by intermittent hypoxia. We aimed to determine whether Trk receptor activation is required for plasticity of upper airway motor outflow induced by repeated obstructive apneas that mimic those experienced in obstructive sleep apnea (OSA). We show that Trk receptor inhibition on hypoglossal motor neurons prevents long-term enhancement of genioglossus muscle tone triggered by repeated airway obstructions in rats. Our result suggests that plasticity of upper airway motor outflow requires a functional neurotrophic signaling cascade. Triggering motor plasticity of upper airways via pharmacological mechanisms could be a potentially useful strategy for improving airway patency in OSA.
Tadjalli
Arash
A
Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada. arash.tadjalli@utoronto.ca
Peever
John
J
D000818:Animals; D007002:Hypoglossal Nerve / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D017551:Microdialysis; D009414:Nerve Growth Factors / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D012891:Sleep Apnea Syndromes / Q000378:metabolism / Q000503:physiopathology; D012965:Sodium Chloride
D009414:Nerve Growth Factors; D012965:Sodium Chloride; D020794:Receptor Protein-Tyrosine Kinases