Cross motor innervation of the hypoglossal nerve-a pilot study of predictors for successful opening of the soft palate.

PURPOSE: Selective hypoglossal nerve stimulation has proven to be a successful treatment option in patients with obstructive sleep apnea. The aim of this pilot study was to investigate if there is a cross-innervation of the hypoglossal nerve in humans and if patients with this phenotype show a different response to hypoglossal nerve stimulation compared to those with ipsilateral-only innervation METHODS: Nineteen patients who previously received a selective hypoglossal nerve stimulation system (Inspire Medical Systems, Golden Valley, USA) were implanted with a nerve integrity system placing electrodes on both sides of the tongue. Tongue motions were recorded one and two months after surgery from transoral and transnasal views. Polysomnography (PSG) was also performed at two months. Electromyogram (EMG) signals and tongue motions after activation were compared with PSG findings. RESULTS: Cross-innervation showed significant correlation with bilateral tongue movement and bilateral tongue base opening, which were associated with better PSG outcomes. CONCLUSION: Cross motor innervation of the hypoglossal nerve occurs in approximately 50% of humans, which is associated with a positive effect on PSG outcomes. Bilateral stimulation of the hypoglossal nerve may be a solution for non-responding patients with pronounced collapse at the soft palate during drug-induced sleep endoscopy.

Innervation of human soft palate muscles.

Our objective was to determine the branching and distribution of the motor nerves supplying the human soft palate muscles. Six adult specimens of the soft palate in continuity with the pharynx, larynx, and tongue were processed with Sihler's stain, a technique that can render large specimens transparent while counterstaining their nerves. The cranial nerves were identified and dissection followed their branches as they divided into smaller divisions toward their terminations in individual muscles. The results showed that both the glossopharyngeal (IX) and vagus (X) nerves have three distinct branches, superior, middle, and inferior. Only the middle branches of each nerve contributed to the pharyngeal plexus to which the facial nerve also contributed. The pharyngeal plexus was divided into two parts, a superior innervating the palatal and neighboring muscles and an inferior innervating pharyngeal constrictors. The superior branches of the IX and X nerves contributed innervation to the palatoglossus, whereas their middle branches innervated the palatopharyngeus. The palatoglossus and palatopharyngeus muscles appeared to be composed of at least two neuromuscular compartments. The lesser palatine nerve not only supplied the palatal mucosa and palatine glandular tissue but also innervated the musculus uvulae, palatopharyngeus, and levator veli palatine. The latter muscle also received its innervation from the superior branch of X nerve. The findings would be useful for better understanding the neural control of the soft palate and for developing novel neuromodulation therapies to treat certain upper airway disorders such as obstructive sleep apnea.

Cell-Autonomous Autophagy Protects Against Chronic Intermittent Hypoxia Induced Sensory Nerves and Endothelial Dysfunction of the Soft Palate.

BACKGROUND Chronic intermittent hypoxia (CIH) is a key feature of obstructive sleep apnea (OSA) syndrome. The pathogenesis of CIH-induced soft palate lesion is not well understood. Understanding the mechanisms of CIH-induced soft palate damage could provide new strategies for clinical treatment. MATERIAL AND METHODS Twenty male Sprague­Dawley rats were randomized into a control group (n=10) and experimental group (n=10). The experimental group were exposed to CIH for 28 days. The control experiments were run in parallel. Morphological changes of CIH-induced soft palate were examined by hematoxylin and eosin. Peripheral nerves and vascular associated markers were analyzed by western blot and immunohistochemical staining. LC3B expression and transmission electron microscopy analysis was detected to investigate the destiny of cells in CIH-induced soft palate. RESULTS Histological studies demonstrated the thicken mucosal layer, muscular changes consistent with glands hyperplasia, and loose connective tissues of the soft palate in CIH induced rat models. CIH exposure significantly decreased the expression of annexin V but did not change argin level, suggesting that sensory nerves not motor nerves were damaged when exposed to intermittent hypoxia. Moreover, in response to CIH, the vascular vessel around the nerves and muscles became enlarged and caveolin-1 was overexpressed. Autophagy occurs in response to CIH-induced neuromuscular and vascular endothelial injury. CONCLUSIONS Sensory nerves and endothelial dysfunction contributed to the morphological damage of soft palate under intermittent hypoxia. Autophagy as a compensatory mechanism protects against CIH-induced injury. These findings have important implications for understanding mechanisms contributing to the increased soft palate lesion in patients with OSA.

Palatal Sensory Function Worsens in Untreated Snorers but not in CPAP-Treated Patients With Sleep Apnea, Indicating Vibration-Induced Nervous Lesions.

BACKGROUND: Signs of both motor and sensory nervous lesions have previously been shown in the upper airway of patients with OSA and habitual snorers. Snoring per se may damage all upper airway neurons over time, thereby causing progression to manifest sleep apnea. To test this hypothesis, nonsnoring subjects, untreated snorers, and CPAP-treated patients underwent repeated sensory testing of the soft palate in a prospective long-term study. METHODS: Cold detection threshold (CDT) testing at the soft palate and lip with a thermode and nocturnal respiratory recordings were performed in 2008 to 2009 with retesting 6 to 7 years later. RESULTS: In 25 untreated snorers, palatal CDT worsened from a median (25th-75th percentile range) 4.2°C (3.2-5.9) to 11.0°C (7.0-17.4) (P < .001). The apnea-hypopnea index increased from a median 7.0 to 14.0 events/h (P < .05). There was no significant correlation between changes in CDT and the apnea-hypopnea index. In 21 nonsnoring control subjects, palatal CDT increased from a median 3.2°C to 5.6°C (P < .005). In 19 CPAP-treated patients, palatal CDT did not significantly change; eight patients had improved values. CDTs worsened significantly more in the snorers group than in the control subjects (P < .05) and the CPAP-treated patients (P < .001). There was no significant difference between control subjects and CPAP-treated patients. CONCLUSIONS: CDT worsened considerably over time in untreated snorers, significantly more than in nonsnoring control subjects and CPAP-treated patients. Untreated snorers therefore risk developing poor sensitivity in the upper airway. In contrast, efficient treatment of OSA seems to protect the sensory innervation, as the CPAP-treated group maintained their sensitivity to cold and, in some cases, the sensitivity even improved.

Quantitative Evaluation of the Function of the Sensory Nerve Fibers of the Palate in Patients With Obstructive Sleep Apnea.

STUDY OBJECTIVES: To quantitatively evaluate the functional integrity of sensory nerve fibers of the palate in patients with obstructive sleep apnea (OSA) using the Neurometer system. METHODS: A total of 32 patients with OSA and 18 healthy control patients were included in the study. All participants were selected based on medical history, physical examination, and nocturnal polysomnography (PSG) and divided into two groups. The palatal sensory status of participants was examined with a Neurometer current perception threshold (CPT) system. The system was used to deliver an electrical stimulus at three different frequencies (2,000 Hz, 250 Hz, and 5 Hz) by an investigator blinded to the PSG results. RESULTS: There were no significant differences in the CPT values of the hard palate between the patients with OSA and control patients at any of the three stimulation frequencies. The differences in the CPT values of the soft palate between these groups failed to show any statistical significance at 250 Hz and 5 Hz. However, the patients with OSA showed significantly higher CPT values of the soft palate at 2,000 Hz than the age-matched healthy control patients (256.56 ± 129.34 versus 372.13 ± 152.06; P = .009). CONCLUSIONS: Our study revealed an impairment of 2,000 Hz-related sensory nerve function of the soft palate among patients with OSA. The CPT test could be a useful tool for the quantitative and selective assessment of the sensory nerve function in patients with OSA. Additional research is required to evaluate the different types of sensory nerve dysfunctions among such patients. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: The Effects of Nasal Airflow on Upper Airway Dilator Muscles During Sleep; Identifier: NCT03506178; URL: https://clinicaltrials.gov/ct2/show/NCT03506178. CITATION: An Y, Li Y, Chang W, Gao F, Ding X, Xu W, Han D. Quantitative evaluation of the function of the sensory nerve fibers of the palate in patients with obstructive sleep apnea. J Clin Sleep Med. 2019;15(9):1347-1353.

Species generalization and differences in Hedgehog pathway regulation of fungiform and circumvallate papilla taste function and somatosensation demonstrated with sonidegib.

Species generalization in the profound, modality-specific effects of Hedgehog pathway inhibition (HPI) in taste organ homeostasis and sensation is shown. With the HPI, cancer drug sonidegib, we demonstrate that the rat taste system, in addition to mouse, is regulated by Hedgehog signaling. After sonidegib treatment for 16-36 days in rat, there is loss of taste buds (TB) in soft palate, in fungiform (FP) and circumvallate papillae (CV), and elimination of taste responses from chorda tympani and glossopharyngeal nerves. The retained innervation in FP and CV during HPI cannot sustain TB. Responses to tactile stimuli are not altered, and temperature responses are reduced only after 28 days treatment, demonstrating modality-specific effects. Rat FP and neural effects are similar to those in mouse whereas TB and neural response effects from the rat CV are much more severe. When recovery is introduced in mouse after prolonged, 48 days HPI, the TB in CV are restored whereas those in FP are not. Overall, Hedgehog signaling regulation is shown to generalize to the rat taste system, and the modality-specific controls in taste organ sensation are affirmed. The reported, debilitating taste disturbances in patients who use HPI drugs can be better understood based on these data.

Sensory Innervation of the Human Soft Palate.

The human soft palate plays an important role in respiration, swallowing, and speech. These motor activities depend on reflexes mediated by sensory nerve endings. To date, the details of human sensory innervation to the soft palate have not been demonstrated. In this study, eight adult human whole-mount (soft palate-tongue-pharynx-larynx-upper esophagus) specimens were obtained from autopsy. Each specimen was bisected in the midline, forming two equal and symmetrical halves. Eight hemi-specimens were processed with Sihler's stain, a whole-mount nerve staining technique. The remaining eight hemi-soft palates were used for immunohistochemical study. The soft palatal mucosa was dissected from the oral and nasal sides and prepared for neurofilament staining. Our results showed that the sensory nerve fibers formed a dense nerve plexus in the lamina propria of the soft palatal mucosa. There was a significant difference in the innervation density between both sides. Specifically, the oral side had higher density of sensory nerve fibers than the nasal side of the soft palate. The mean number and percent area of the sensory nerve fibers in the mucosa of the nasal side was 78% and 72% of those in the mucosa of the oral side, respectively (P < 0.0001). The data presented here could be helpful for further investigating the morphological and quantitative alterations in the sensory nerves in certain upper airway disorders involving the soft palate such as obstructive sleep apnea (OSA) and for designing effective therapeutic strategies to treat OSA. Anat Rec, 301:1861-1870, 2018. © 2018 Wiley Periodicals, Inc.

Axon and Schwann Cell Degeneration in Nerves of Upper Airway Relates to Pharyngeal Dysfunction in Snorers and Patients With Sleep Apnea.

BACKGROUND: The pathophysiologic mechanism of nocturnal obstruction and swallowing dysfunction commonly occurring in patients with sleep apnea is unclear. The goal of this study was to investigate whether nerve injuries in the upper airways of snorers and patients with sleep apnea are associated with pharyngeal dysfunction and severity of sleep apnea. METHODS: Twenty-two patients undergoing palatal surgery due to snoring and sleep apnea were investigated for a swallowing dysfunction by using videoradiography. Twelve healthy nonsnoring subjects were included as control subjects. Tissue samples from the soft palate at the base of the uvula were obtained in all patients and control subjects. Nerves and muscle were analyzed with immunohistochemical and morphologic methods, and the findings were correlated with swallowing function and degree of sleep apnea. RESULTS: In the soft palate of patients, nerve fascicles exhibited a significantly lower density of axons (5.4 vs 17.9 × 10-3 axons/µm2; P = .02), a smaller percentage area occupied by Schwann cells (17.5% vs 45.2%; P = .001) and a larger number of circular shaped Schwann cells lacking central axons (43.0% vs 12.7%; P < 0.001) compared with control subjects. The low density of axons was significantly related to degree of swallowing dysfunction (r = 0.5; P = .03) and apnea-hypopnea index > 5 (P = .03). Regenerating axons were frequently observed in patients compared with control subjects (11.3 ± 4.2% vs 4.8 ± 2.4%; P = .02). CONCLUSIONS: Axon degeneration in preterminal nerves of the soft palate is associated with pharyngeal dysfunction in snorers and patients with sleep apnea. The most likely cause for the nerve injuries is traumatic snoring vibrations and tissue stretch, leading to swallowing dysfunction and increased risk for upper airway obstruction during sleep.

The relationship of the uvula with snoring and obstructive sleep apnea: a systematic review.

Currently, the relationship between uvula size and sleep-disordered breathing (snoring and obstructive sleep apnea) lacks data for objective interpretation. This study conducted a systematic review of the international literature for research describing the measurable characteristics of the uvula (i.e., size, length, width) and any association with snoring and obstructive sleep apnea (OSA). PubMED, Scopus, Google Scholar, Embase, and the Cochrane Library were each systematically searched from inception through November 15, 2016. We screened 1037 titles and abstracts. We conducted a full review of 54 downloaded articles. Sixteen articles met inclusion and exclusion criteria. The 16 studies included a total of 2604 patients. The selected articles included data and information for (1) normative data for uvular size in the control groups, (2) snoring and uvula size, (3) OSA and uvula size, and (4) overall uvula function. Our review noted variability in findings; however, in general, a uvular length > 15 mm was considered elongated and a uvular width > 10 mm was considered to be wide. The studies included in this systematic review reveal a relationship between uvula size, snoring, and OSA. Further, larger uvulas appear associated with more severe snoring and OSA. The direct correlation between uvula size and its relationship specifically to snoring and OSA remain as topics for future prospective research.

Neuromuscular function of the soft palate and uvula in snoring and obstructive sleep apnea: A systematic review.

OBJECTIVE: A collapsible upper airway is a common cause of obstructive sleep apnea. The exact pathophysiology leading to a more collapsible airway is not well understood. A progressive neuropathy of the soft palate and pharyngeal dilators may be associated with the progression of snoring to OSA. The purpose of this study is to systematically review the international literature investigating the neurophysiologic changes in the soft palate and uvula that contribute to progression from snoring to OSA. METHODS: PubMed/MEDLINE and 4 other databases were systematically searched through July 4, 2017. Eligibility: (1) Patients: controls, snoring or OSA patients (2) Intervention: neuromuscular evaluation of the palate and/or uvula (3) Comparison: differences between controls, snoring and OSA patients (4) Outcomes: neuromuscular outcomes (5) Study design: Peer reviewed publications of any design. RESULTS: 845 studies were screened, 76 were downloaded in full text form and thirty-one studies met criteria. Histological studies of the soft palate demonstrated diffuse inflammatory changes, muscular changes consistent with neuropathy, and neural aberrancies. Sensory testing studies provided heterogeneous outcomes though the majority favored neuronal dysfunction. Studies have consistently demonstrated that increasing severity of snoring and sleep apnea is associated with worsening sensory nerve function of the palate in association with atrophic histological changes to the nerves and muscle fibers of the soft palate and uvula. CONCLUSIONS: Recent evidence highlighted in this systematic review implicates the role of neurogenic pathology underlying the loss of soft palate and/or uvular tone in the progression of snoring to sleep apnea.

Idiopathic Unilateral Paralysis of the Palate in a Youth.

Unilateral isolated paralysis of the soft palate is a rare clinical entity that is associated with rhinolalia and the flow of nasal fluids from the nostril on the affected side. We report a case of a 17-year-old boy admitted complaining of nasal speech and drinks flowing into his right nostril. Most cases of soft palate palsy are idiopathic, whereas a few cases are caused by viral infections or tumors. We describe an isolated case of soft palate palsy with spontaneous recovery within 1 month.

Morphological observation and CBCT of the bony canal structure of the groove and the location of blood vessels and nerves in the palatine of elderly human cadavers.

PURPOSE: The greater and lesser palatine nerves and vessels supply the hard and soft palates, and the roots of these vessels and nerves run through a bony structure. However, the arrangement of blood vessels in the maxilla requires attention during clinical treatments, but detailed morphological information about changes in the greater and lesser palatine arteries and nerves during aging is unavailable. We therefore need detailed investigations of the morphology of the donor cadaver palatine using cone-beam computed tomography (CBCT) and macroscopic observations. METHODS: We investigated 72 donor cadavers using macroscopic segmentation and CBCT. The results' analysis examined differences in skull measurement parameters and differences between dentate and edentulous cases. RESULTS: The greater palatine artery and nerve showed different macroscopic arrangements in dentate and edentulous cadavers. We also classified three types of bony structures of the nerve and vessel roots in the molar regions of the palatine using CBCT images: the shallow groove, deep groove, and flat groove. The deep groove is the deepest of the three and is remarkable in edentulous elderly cadavers. CONCLUSION: This study of macroscopic and CBCT data provides information useful for planning dental implant surgeries and autogenous bone harvesting.

Palatoglossus coupling in selective upper airway stimulation.

OBJECTIVES/HYPOTHESIS: Selective upper airway stimulation (sUAS) of the hypoglossal nerve is a useful therapy to treat patients with obstructive sleep apnea. Is it known that multiple obstructions can be solved by this stimulation technique, even at the retropalatal region. The aim of this study was to verify the palatoglossus coupling at the soft palate during stimulation. STUDY DESIGN: Single-center, prospective clinical trail. METHODS: Twenty patients who received an sUAS implant from April 2015 to April 2016 were included. A drug-induced sedated endoscopy (DISE) was performed before surgery. Six to 12 months after activation of the system, patients' tongue motions were recorded, an awake transnasal endoscopy was performed with stimulation turned on, and a DISE with stimulation off and on was done. RESULTS: Patients with a bilateral protrusion of the tongue base showed a significantly increased opening at the retropalatal level compared to ipsilateral protrusions. Furthermore, patients with a clear activation of the geniohyoid muscle showed a better reduction in apnea-hypopnea index. CONCLUSIONS: A bilateral protrusion of the tongue base during sUAS seems to be accompanied with a better opening of the soft palate. This effect can be explained by the palatoglossal coupling, due to its linkage of the muscles within the soft palate to those of the lateral tongue body. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:E378-E383, 2017.

Functional and Quantitative MRI Mapping of Somatomotor Representations of Human Supralaryngeal Vocal Tract.

Speech articulation requires precise control of and coordination between the effectors of the vocal tract (e.g., lips, tongue, soft palate, and larynx). However, it is unclear how the cortex represents movements of and contact between these effectors during speech, or how these cortical responses relate to inter-regional anatomical borders. Here, we used phase-encoded fMRI to map somatomotor representations of speech articulations. Phonetically trained participants produced speech phones, progressing from front (bilabial) to back (glottal) place of articulation. Maps of cortical myelin proxies (R1 = 1/T1) further allowed us to situate functional maps with respect to anatomical borders of motor and somatosensory regions. Across participants, we found a consistent topological map of place of articulation, spanning the central sulcus and primary motor and somatosensory areas, that moved from lateral to inferior as place of articulation progressed from front to back. Phones produced at velar and glottal places of articulation activated the inferior aspect of the central sulcus, but with considerable across-subject variability. R1 maps for a subset of participants revealed that articulator maps extended posteriorly into secondary somatosensory regions. These results show consistent topological organization of cortical representations of the vocal apparatus in the context of speech behavior.

Sensory Topography of Oral Structures.

Importance: Sensory function in the oral cavity and oropharynx is integral to effective deglutition and speech production. The main hurdle to evaluation of tactile consequences of upper aerodigestive tract diseases and treatments is access to a reliable clinical tool. We propose a rapid and reliable procedure to determine tactile thresholds using buckling monofilaments to advance care. Objective: To develop novel sensory testing monofilaments and map tactile thresholds of oral cavity and oropharyngeal structures. Design, Setting, and Participants: A prospective cross-sectional study of 37 healthy adults (12 men, 25 women), specifically without a medical history of head and neck surgery, radiation, or chemotherapy, was carried out in an academic tertiary medical center to capture normative data on tactile sensory function in oral structures. Interventions: Cheung-Bearelly monofilaments were constructed by securing nylon monofilament sutures (2-0 through 9-0) in the lumen of 5-French ureteral catheters, exposing 20 mm for tapping action. Main Outcomes and Measures: Buckling force consistency was evaluated for 3 lots of each suture size. Sensory thresholds of 4 oral cavity and 2 oropharyngeal subsites in healthy participants (n = 37) were determined by classical signal detection methodology (d-prime ≥1). In 21 participants, test-retest reliability of sensory thresholds was evaluated. Separately in 16 participants, sensory thresholds determined by a modified staircase method were cross-validated with those obtained by classical signal detection. Results: Buckling forces of successive suture sizes were distinct (P < .001), consistent (Cronbach α, 0.99), and logarithmically related (r = 0.99, P < .001). Test-retest reliability of sensory threshold determination was high (Cronbach α, >0.7). The lower lip, anterior tongue, and buccal mucosa were more sensitive than the soft palate, posterior tongue, and posterior pharyngeal wall (P < .001). Threshold determination by classical signal detection and modified staircase methods were highly correlated (r = 0.93, P < .001). Growth of perceptual intensity was logarithmically proportional to stimulus strength (P < .01). Conclusions and Relevance: Topography of normal oral cavity and oropharyngeal tactile sensation is organized in accordance to decreasing sensitivity along the anteroposterior trajectory and growth of perceptual intensity at all subsites is log-linear. Cheung-Bearelly monofilaments are accessible, disposable, and consistent esthesiometers. This novel clinical tool is deployable for quantitative sensory function assessment of oral cavity and oropharyngeal structures.

The innervation of the soft palate muscles involved in cleft palate: a review of the literature.

OBJECTIVE: Surgical techniques to obtain adequate soft palate repair in cleft palate patients elaborate on the muscle repair; however, there is little available information regarding the innervation of muscles. Improved insights into the innervation of the musculature will likely allow improvements in the repair of the cleft palate and subsequently decrease the incidence of velopharyngeal insufficiency. We performed a literature review focusing on recent advances in the understanding of soft palate muscle innervation. MATERIAL AND METHODS: The Medline and Embase databases were searched for anatomical studies concerning the innervation of the soft palate. RESULTS: Our literature review highlights the lack of accurate information about the innervation of the levator veli palatini and palatopharyngeus muscles. It is probable that the lesser palatine nerve and the pharyngeal plexus dually innervate the levator veli palatini and palatopharyngeus muscles. Nerves of the superior-extravelar part of the levator veli palatini and palatopharyngeus muscles enter the muscle form the lateral side. Subsequently, the lesser palatine nerve enters from the lateral side of the inferior-velar part of the levator veli palatini muscle. This knowledge could aid surgeons during reconstruction of the cleft musculature. The innervation of the tensor veli palatini muscle by a small branch of the mandibular nerve was confirmed in all studies. CONCLUSION: Both the levator veli palatini and palatopharyngeus muscles receive motor fibres from the accessory nerve (through the vagus nerve and the glossopharyngeal nerve) and also the lesser palatine nerve. A small branch of the mandibular nerve innervates the tensor veli palatini muscle. CLINICAL RELEVANCE: Knowledge about these nerves could aid the cleft surgeon to perform a more careful dissection of the lateral side of the musculature.

Histopathologic and immunohistochemical features of soft palate muscles and nerves in dogs with an elongated soft palate.

OBJECTIVE: To histologically evaluate and compare features of myofibers within the elongated soft palate (ESP) of brachycephalic and mesocephalic dogs with those in the soft palate of healthy dogs and to assess whether denervation or muscular dystrophy is associated with soft palate elongation. SAMPLE: Soft palate specimens from 24 dogs with ESPs (obtained during surgical intervention) and from 14 healthy Beagles (control group). PROCEDURES: All the soft palate specimens underwent histologic examination to assess myofiber atrophy, hypertrophy, hyalinization, and regeneration. The degrees of atrophy and hypertrophy were quantified on the basis of the coefficient of variation and the number of myofibers with hyalinization and regeneration. The specimens also underwent immunohistochemical analysis with anti-neurofilament or anti-dystrophin antibody to confirm the distribution of peripheral nerve branches innervating the palatine myofibers and myofiber dystrophin expression, respectively. RESULTS: Myofiber atrophy, hypertrophy, hyalinization, and regeneration were identified in almost all the ESP specimens. Degrees of atrophy and hypertrophy were significantly greater in the ESP specimens, compared with the control specimens. There were fewer palatine peripheral nerve branches in the ESP specimens than in the control specimens. Almost all the myofibers in the ESP and control specimens were dystrophin positive. CONCLUSIONS AND CLINICAL RELEVANCE: These results suggested that palatine myopathy in dogs may be caused, at least in part, by denervation of the palatine muscles and not by Duchenne- or Becker-type muscular dystrophy. These soft palate changes may contribute to upper airway collapse and the progression of brachycephalic airway obstructive syndrome.

A Comprehensive Study of Soft Palate Development in Mice.

Cleft palate is one of the most common congenital birth defects. Tremendous efforts have been made over the last decades towards understanding hard palate development. However, little is known about soft palate morphogenesis and myogenesis. Finding an appropriate surgical repair to restore physiological functions of the soft palate in patients with cleft palate is a major challenge for surgeons, and complete restoration is not always achievable. Here, we first analyzed the morphology, orientation and attachments of the four muscles of the murine soft palate and found that they are very similar to their counterparts in humans, validating the use of mus musculus as a model for future studies. Our data suggests that muscle differentiation extends from the lateral region to the midline following palatal fusion. We also detected an epithelial seam in the fusing soft palatal shelves, consistent with the process of fusion of the posterior palatal shelves, followed by degradation of the epithelial remnants. Innervation and vascularization are present mainly in the oral side of the soft palate, complementing the differentiated muscles. Cell lineage tracing using Wnt1-Cre;Zsgreenfl/fl mice indicated that all the tendons and mesenchyme embedding the soft palate muscles are neural crest-derived. We propose that the posterior attachment of the soft palate to the pharyngeal wall is an interface between the neural crest- and mesoderm-derived mesenchyme in the craniofacial region, and thus can serve as a potential model for the study of boundaries during development. Taken together, our study provides a comprehensive view of the development and morphology of the murine soft palate and serves as a reference for further molecular analyses.

Decline of umami preference in aged rats.

The effects of aging on the umami sensation were compared between the preference and neural responses from the greater superficial petrosal nerve (GSP innervating the soft palate) and the chorda tympani nerve (CT innervating the fungiform papillae) in the Sprague Dawley rat. A two-bottle preference test revealed that younger rats (5-12 weeks) preferred significantly 0.001 M 5'-inosine monophosphate (IMP), 0.01 M mono sodium glutamate (MSG), and binary mixtures of 0.001 M IMP+0.01 M MSG than deionized water. However, aged rats (21-22 months) showed no significant preference to these umami solutions compared to deionized water. Among the other four basic taste stimuli, there were no significant differences in preference between young and aged rats. Regardless of the age of the rat, neural responses from the GSP and CT produced robust integrated responses to all three umami solutions used in the two-bottle tests. These results indicate that the lack of preference to umami in aged rats is a central nervous system phenomenon and suggests that the loss of preference to umami taste in aged rats is caused by homeostatic changes in the brain incurred by aging.

Diverse contributions of Tas1r2/Tas2rs within the rat and mouse soft palate to sweet and bitter neural responses.

Neural responses to sweet and bitter stimuli in the rat and mouse are compared to the expression of the molecular taste receptors, Tas1r2/Tas2rs. Integrated taste responses from the greater superficial petrosal nerve (GSP) innervating the soft palate (SP) and the chorda tympani (CT) nerve innervating the fungiform papillae (FF) were recorded in C57BL mice and SD rats. The sum of the phasic and tonic response magnitudes (SRM) was calculated by summating all relative mean responses to a concentration series of QHCl (10(-6)-10(-2)M) or Suc (10(-4)-1.0M). Molecular expression was analyzed by double-colored in situ hybridization for Gα-gustducin with Tas1r2 or Tas2rs in the SP and FF. The vast majority of cells expressing Tas1r2 or Tas2rs were included in Gα-gustducin-expressing cells in the SP of both species. Unexpectedly, a comparison between species revealed that the SRM from the GSP is not positively correlated with receptor expression in the SP. In the rat SP, the percentage of Tas2rs with Gα-gustducin (Tas2rs/gust, 65%) was twice larger than that for Tas1r2/gust (33%), while the SRM to Suc in the rat GSP was 1.5 times (tonic and phasic) larger than that to QHCl. In the mouse SP, the percentage of Tas2rs/gust (46%) was less than that in the rat and similar to that of Tas1r2/gust (40%). However, the SRM to QHCl in the mouse GSP was 2.4 (phasic) and 4.7 (tonic) times larger than to Suc. On the other hand, threshold to Suc in the rat GSP was 10(-3)M, one log unit lower than in mouse, and the threshold to QHCl in the mouse GSP was 10(-6)M, one log unit lower than in rat. These results suggest that the robust GSP response to Suc in rat and to QHCl in mouse likely do not depend upon a large number of taste cells expressing the taste receptors Tas1r2 for Suc or Tas2rs for QHCl, but upon a higher density of Tas1r2/Tas2rs within the respective taste cells of the two species.