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[This corrects the article DOI: 10.1371/journal.pone.0249904.].

Abstract Introduction In obstructive sleep apnea (OSA) patients, hyperactivity of the tongue muscles protects the upper airway against occlusions during wakefulness. Tongue task training in human was associated with plasticity of corticomotor excitability of Genioglossus. Since rats subjected to tongue exercise revealed increased serotonergic input to the hypoglossal nucleus, this study aimed to investigate whether these anatomic indexes of increased serotonergic innervation could translate into increased sensitivity of genioglossus activity to serotonergic activation. Methods 18 water-restricted adult male Sprague-Dawley rats were trained to lick an isometric force-sensing disc at targeting forces (30–50% maximal protrusion force) for water reinforcement with sound feedback. The rats in Tongue motor-oriented Task Training (TTT) group were trained daily for two month, and the training intensity was fixed by a total tongue muscle work of 1000 g·s per day. 24 hours after 8-weeks-training, rats were anesthetized, vagotomized and paralyzed. The dorsal medulla was exposed, and 5-HTP (5 mM, 20 nl) or 5-HT2A receptor antagonist ketanserin (1 mM, 3 x 40nl) were microinjected into the XII nucleus while genioglossus electromyographic (EMG) activity was recorded. The EMG-root mean square values was measured before and at different times after microinjections. Results The excitatory effect of 5-HTP on the tonic genioglossus EMG activity was similar in sham- and TTT-treated rats within 20 minutes after injection, while this excitability maintained up to 40 minutes only in TTT-treated rats. In contrast, the tonic genioglossus EMG activity was more profoundly reduced 30 minutes following ketanserin injections in TTT- than sham-treated rats [36% ± 7% vs. 78 ± 11%, p < 0.05], without significant changes in central respiratory rate or heart rate. Conclusion Consistent with increased neuroanatomic measures of serotonergic innervation of XII nucleus following tongue training, ketanserin microinjections revealed a stronger endogenous serotonergic excitatory drive to genioglossus activity in TTT- than sham-treated anesthetized rats. These results could have implications for treatment paradigms related to enhancement of central neuromuscular output of tongue for OSA patients. Support (If Any) Supported by Liaoning (China) Institutes of Innovation Team, Grant LT 2013015.

BackgroundOsteogenesis imperfecta (OI) is most often caused by mutations in type I collagen genes. Respiratory complications have been largely attributed to spine and ribcage deformities. We hypothesized that direct involvement of the pulmonary parenchyma and/or diaphragm by the disease may occur.MethodsIn Col1a1Jrt/+ mice, a model of severe dominant OI, mean linear intercept length (Lm) was used to assess the distal airspace size. Cross-sectional area (CSA) and myosin heavy chain (MyHC) phenotype of the diaphragm muscle fibers, as well as contractile properties, were determined. OI mice were also treated with neutralizing antibodies against transforming growth factor-β (TGF-β).ResultsDistal airspace enlargement occurred in OI mice (Lm +27%). Diaphragmatic thickness and fiber number were reduced, with increases in fast-twitch type IIx/IIb MyHC fibers. Ex vivo force generation (normalized for CSA) of the diaphragm was also significantly reduced. The increased Lm values found in OI mice were not prevented by anti-TGF-β antibody treatment.ConclusionsThe Col1a1Jrt/+ mouse model of OI demonstrates: (1) pulmonary airspace enlargement not driven by TGF-β; and (2) reduced muscle mass and intrinsic contractile weakness of the diaphragm. These results suggest a complex and multifaceted basis for respiratory complications in OI that cannot be solely attributed to bone manifestations.