Objectives Obesity hypoventilation syndrome and obstructive sleep apnea are common complications of obesity linked to defects in respiratory pump and upper airway neural *** deficient ob/ob mice have impaired hypercap...
Objectives Obesity hypoventilation syndrome and obstructive sleep apnea are common complications of obesity linked to defects in respiratory pump and upper airway neural *** deficient ob/ob mice have impaired hypercapnic ventilatory response and inspiratory flow limitation during sleep,which are both reversed with *** study is to localize CNS site(s) of leptin action on respiratory and upper airway neuro-ventilatory *** We localized the effect of leptin to medulla *** by administering intracerbroventricular leptin(10μg/2ul)vs vehicle to the lateral(n=14)vs fourth ventricle(n=11)of ob/ob mice followed by a 6 h polysomnographic *** were stratified for effects on respiratory(non-flow limited breaths) and upper airway(inspiratory flow limitation) *** loci were identified by(a) leptin-induced STAT3 phosphorylation and(b)projections of respiratory and upper airway motoneurons with a retrograde tracer pseudorabies *** Both routes of leptin administration increased minute ventilation during non-flow limited breathing in *** motoneurons projected to the nucleus of the solitary tract,which showed STAT3 phosphorylation,but not to the *** flow limitation and obstructive hypopneas were attenuated by leptin administration to the lateral,but not to the fourth cerebral *** airway motoneurons projected to the dorsomedial hypothalamus,which exhibited STAT3 *** Leptin relieves upper airway obstruction in sleep apnea by activating the forebrain,possibly in the dorsomedial *** contrast,leptin up-regulates ventilatory control through hindbrain sites of action,possibly in the nucleus of the solitary tract.
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