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1.
Proc Natl Acad Sci U S A ; 120(22): e2217595120, 2023 05 30.
Article in English | MEDLINE | ID: mdl-37216536

ABSTRACT

The sense of taste starts with activation of receptor cells in taste buds by chemical stimuli which then communicate this signal via innervating oral sensory neurons to the CNS. The cell bodies of oral sensory neurons reside in the geniculate ganglion (GG) and nodose/petrosal/jugular ganglion. The geniculate ganglion contains two main neuronal populations: BRN3A+ somatosensory neurons that innervate the pinna and PHOX2B+ sensory neurons that innervate the oral cavity. While much is known about the different taste bud cell subtypes, considerably less is known about the molecular identities of PHOX2B+ sensory subpopulations. In the GG, as many as 12 different subpopulations have been predicted from electrophysiological studies, while transcriptional identities exist for only 3 to 6. Importantly, the cell fate pathways that diversify PHOX2B+ oral sensory neurons into these subpopulations are unknown. The transcription factor EGR4 was identified as being highly expressed in GG neurons. EGR4 deletion causes GG oral sensory neurons to lose their expression of PHOX2B and other oral sensory genes and up-regulate BRN3A. This is followed by a loss of chemosensory innervation of taste buds, a loss of type II taste cells responsive to bitter, sweet, and umami stimuli, and a concomitant increase in type I glial-like taste bud cells. These deficits culminate in a loss of nerve responses to sweet and umami taste qualities. Taken together, we identify a critical role of EGR4 in cell fate specification and maintenance of subpopulations of GG neurons, which in turn maintain the appropriate sweet and umami taste receptor cells.


Subject(s)
Taste Buds , Taste , Taste/physiology , Geniculate Ganglion/metabolism , Tongue/innervation , Taste Buds/metabolism , Transcription Factors/metabolism , Sensory Receptor Cells/metabolism
2.
Neuroradiology ; 65(10): 1425-1438, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37540288

ABSTRACT

CT and MRI findings of tongue ptosis and atrophy should alert radiologists to potential pathology along the course of the hypoglossal nerve (cranial nerve XII), a purely motor cranial nerve which supplies the intrinsic and extrinsic muscles of the tongue. While relatively specific for hypoglossal nerve pathology, these findings do not accurately localize the site or cause of denervation. A detailed understanding of the anatomic extent of the nerve, which crosses multiple anatomic spaces, is essential to identify possible underlying pathology, which ranges from benign postoperative changes to life-threatening medical emergencies. This review will describe key imaging findings of tongue denervation, segmental anatomy of the hypoglossal nerve, imaging optimization, and comprehensive imaging examples of diverse pathology which may affect the hypoglossal nerve. Armed with this knowledge, radiologists will increase their sensitivity for detection of pathology and provide clinically relevant differential diagnoses when faced with findings of tongue ptosis and denervation.


Subject(s)
Hypoglossal Nerve , Tongue , Humans , Hypoglossal Nerve/anatomy & histology , Hypoglossal Nerve/pathology , Tongue/diagnostic imaging , Tongue/innervation , Tongue/pathology , Magnetic Resonance Imaging
3.
Cell Mol Life Sci ; 79(4): 211, 2022 Mar 27.
Article in English | MEDLINE | ID: mdl-35344108

ABSTRACT

Taste stem/progenitor cells from posterior mouse tongues have been used to generate taste bud organoids. However, the inaccessible location of taste receptor cells is observed in conventional organoids. In this study, we established a suspension-culture method to fine-tune taste bud organoids by apicobasal polarity alteration to form the accessible localization of taste receptor cells. Compared to conventional Matrigel-embedded organoids, suspension-cultured organoids showed comparable differentiation and renewal rates to those of taste buds in vivo and exhibited functional taste receptor cells and cycling progenitor cells. Accessible taste receptor cells enabled the direct application of calcium imaging to evaluate the taste response. Moreover, suspension-cultured organoids can be genetically altered. Suspension-cultured taste bud organoids harmoniously integrated with the recipient lingual epithelium, maintaining the taste receptor cells and gustatory innervation capacity. We propose that suspension-cultured organoids may provide an efficient model for taste research, including taste bud development, regeneration, and transplantation.


Subject(s)
Taste Buds , Animals , Epithelium/physiology , Mice , Organoids , Taste/physiology , Taste Buds/physiology , Tongue/innervation
4.
Clin Anat ; 36(6): 900-904, 2023 Sep.
Article in English | MEDLINE | ID: mdl-36807941

ABSTRACT

The lingual nerve carries somatosensory fibers from the anterior two-thirds of tongue. The parasympathetic preganglionic fibers arising from the chorda tympani also travel with the lingual nerve in the infratemporal fossa to synapse in the submandibular ganglion to innervate the sublingual gland. However, only a few studies have investigated the specific nerve that innervates the sublingual gland and surrounding tissue i.e., the so-called sublingual nerve. Therefore, this study aimed to clarify the anatomy and definition of the sublingual nerves. Thirty sides from formalin fixed cadaveric hemiheads underwent microsurgical dissection of the sublingual nerves. The sublingual nerves were found on all sides and categorized into three branches, i.e., branches to the sublingual gland, branches to the mucosa of the floor of the mouth, and gingival branches. Additionally, branches to the sublingual gland were subcategorized into types I and II based on the origin of the sublingual nerve. We suggest that the lingual nerve branches should be categorized into five branches, i.e., branches to the isthmus of the fauces, sublingual nerves, lingual branches, posterior branch to the submandibular ganglion, and branches to the sublingual ganglion.


Subject(s)
Lingual Nerve , Tongue , Humans , Lingual Nerve/anatomy & histology , Tongue/innervation
5.
Eur J Neurosci ; 56(7): 4967-4982, 2022 10.
Article in English | MEDLINE | ID: mdl-35986485

ABSTRACT

Vismodegib is used in patients suffering from advanced basal cell carcinoma (BCC), but 100% of the patients taking it report dysgeusia and 50% discontinue the treatment. Treatment with neurotrophic factors can stimulate neuronal survival and functional improvement in injured organs. Here, we analysed novel transgenic mouse lines in which brain-derived neurotrophic factor (BDNF) is overexpressed in taste buds, to examine whether higher levels of BDNF would reduce or prevent negative side effects of vismodegib in the taste system. BDNF plays crucial roles for development, target innervation, and survival of gustatory neurons and taste buds. The behavioural test in this study showed that vehicle-treated wild-type mice prefered 10 mM sucrose over water, whereas vismodegib treatment in wild-type mice caused total taste loss. Gustducin-BDNF mice had a significantly increased preference for low concentration of sucrose solution over water compared to wild-type mice, and most importantly the transgenic mice were able to detect low concentrations of sucrose following vismodegib treatment. We evaluated taste cell morphology, identity, innervation and proliferation using immunohistochemistry. All drug-treated mice exhibited deficits, but because of a possible functional upcycled priming of the peripheral gustatory system, GB mice demonstrated better morphological preservation of the peripheral gustatory system. Our study indicates that overexpression of BDNF in taste buds plays a role in preventing degeneration of taste buds. Counteracting the negative side effects of vismodegib treatment might improve compliance and achieve better outcome in patients suffering from advanced BCC.


Subject(s)
Ageusia , Antineoplastic Agents , Brain-Derived Neurotrophic Factor , Taste Buds , Ageusia/chemically induced , Ageusia/metabolism , Anilides , Animals , Antineoplastic Agents/adverse effects , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , Mice , Mice, Transgenic , Pyridines , Sucrose , Taste/physiology , Taste Buds/physiopathology , Tongue/innervation , Tongue/physiopathology
6.
Development ; 146(17)2019 09 06.
Article in English | MEDLINE | ID: mdl-31427287

ABSTRACT

Feeding and breathing are essential motor functions and rely on the activity of hypoglossal and phrenic motor neurons that innervate the tongue and diaphragm, respectively. Little is known about the genetic programs that control the development of these neuronal subtypes. The transcription factor Tshz1 is strongly and persistently expressed in developing hypoglossal and phrenic motor neurons. We used conditional mutation of Tshz1 in the progenitor zone of motor neurons (Tshz1MNΔ) to show that Tshz1 is essential for survival and function of hypoglossal and phrenic motor neurons. Hypoglossal and phrenic motor neurons are born in correct numbers, but many die between embryonic day 13.5 and 14.5 in Tshz1MNΔ mutant mice. In addition, innervation and electrophysiological properties of phrenic and hypoglossal motor neurons are altered. Severe feeding and breathing problems accompany this developmental deficit. Although motor neuron survival can be rescued by elimination of the pro-apoptotic factor Bax, innervation, feeding and breathing defects persist in Bax-/-; Tshz1MNΔ mutants. We conclude that Tshz1 is an essential transcription factor for the development and physiological function of phrenic and hypoglossal motor neurons.


Subject(s)
Homeodomain Proteins/metabolism , Hypoglossal Nerve/cytology , Motor Neurons/physiology , Phrenic Nerve/cytology , Repressor Proteins/metabolism , Animals , Animals, Newborn , Apoptosis/genetics , Cell Survival/genetics , Diaphragm/innervation , Homeodomain Proteins/genetics , Mice , Mice, Transgenic , Mutation , Plethysmography , Repressor Proteins/genetics , Respiration , Tongue/innervation , bcl-2-Associated X Protein/genetics
7.
Neuromodulation ; 25(8): 1312-1316, 2022 Dec.
Article in English | MEDLINE | ID: mdl-34214238

ABSTRACT

OBJECTIVES: Hypoglossal nerve stimulation is an effective treatment option for obstructive sleep apnea (OSA) in positive airway pressure therapy failure. Nonetheless, data regarding the functional effect of modifying stimulation parameters within each electrode configuration are limited. MATERIALS AND METHODS: In a retrospective study of 76 patients with 12 months or more follow-up, functional tongue protrusion thresholds were compared for pulse width and frequency configurations of 90 µsec 33 Hz vs 120 µsec 40 Hz. The number of tolerated voltage amplitude steps between sensation, functional, and subdiscomfort thresholds were assessed for both settings as well as impedances. RESULTS: The overall cohort showed improvement in OSA metrics: median apnea-hypopnea index from 30.0/hour to 18.6/hour and Epworth Sleepiness Scale from 13.5 to 7.6. For both bipolar and unipolar electrode configurations, the stimulation amplitude required for functional tongue protrusion was significantly reduced when the pulse width and frequency were converted from 90 µsec 33 Hz to 120 µsec 40 Hz (p < 0.001). Nevertheless, the number of voltage amplitude steps from sensation, functional, to subdiscomfort thresholds did not differ between the two settings. The ratio of automatically derived impedances between bipolar and unipolar electrode configurations was relevantly correlated with the ratio of functional thresholds at these parameters. CONCLUSION: Changing the stimulation parameters may lower the voltage requirements while maintaining the same effect on tongue protrusion. Changing these stimulation parameters does not affect the range of tolerated impulse steps between functional and subdiscomfort thresholds. Future technical appliances could help estimate functional thresholds at different electrode configurations for each patient by automatically measuring impedances.


Subject(s)
Electric Stimulation Therapy , Sleep Apnea, Obstructive , Humans , Hypoglossal Nerve/physiology , Retrospective Studies , Tongue/innervation , Electric Stimulation Therapy/adverse effects , Sleep Apnea, Obstructive/therapy
8.
Nature ; 517(7534): 373-6, 2015 Jan 15.
Article in English | MEDLINE | ID: mdl-25383521

ABSTRACT

The mammalian taste system is responsible for sensing and responding to the five basic taste qualities: sweet, sour, bitter, salty and umami. Previously, we showed that each taste is detected by dedicated taste receptor cells (TRCs) on the tongue and palate epithelium. To understand how TRCs transmit information to higher neural centres, we examined the tuning properties of large ensembles of neurons in the first neural station of the gustatory system. Here, we generated and characterized a collection of transgenic mice expressing a genetically encoded calcium indicator in central and peripheral neurons, and used a gradient refractive index microendoscope combined with high-resolution two-photon microscopy to image taste responses from ganglion neurons buried deep at the base of the brain. Our results reveal fine selectivity in the taste preference of ganglion neurons; demonstrate a strong match between TRCs in the tongue and the principal neural afferents relaying taste information to the brain; and expose the highly specific transfer of taste information between taste cells and the central nervous system.


Subject(s)
Geniculate Ganglion/cytology , Neurons/physiology , Taste Perception/physiology , Taste/physiology , Tongue/physiology , Animals , Calcium/metabolism , Mice , Mice, Transgenic , Taste Buds/cytology , Taste Buds/physiology , Tongue/cytology , Tongue/innervation
9.
Sleep Breath ; 25(1): 425-431, 2021 Mar.
Article in English | MEDLINE | ID: mdl-32488573

ABSTRACT

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.


Subject(s)
Hypoglossal Nerve/physiology , Palate, Soft/innervation , Electric Stimulation/methods , Female , Humans , Male , Middle Aged , Monitoring, Intraoperative , Motor Neurons/physiology , Palate, Soft/surgery , Pilot Projects , Tongue/innervation , Tongue/physiology
10.
Proc Natl Acad Sci U S A ; 115(3): E516-E525, 2018 01 16.
Article in English | MEDLINE | ID: mdl-29282324

ABSTRACT

The development of the taste system relies on the coordinated regulation of cues that direct the simultaneous development of both peripheral taste organs and innervating sensory ganglia, but the underlying mechanisms remain poorly understood. In this study, we describe a novel, biphasic function for glial cell line-derived neurotrophic factor (GDNF) in the development and subsequent diversification of chemosensory neurons within the geniculate ganglion (GG). GDNF, acting through the receptor tyrosine kinase Ret, regulates the expression of the chemosensory fate determinant Phox2b early in GG development. Ret-/- mice, but not Retfx/fx ; Phox2b-Cre mice, display a profound loss of Phox2b expression with subsequent chemosensory innervation deficits, indicating that Ret is required for the initial amplification of Phox2b expression but not its maintenance. Ret expression is extinguished perinatally but reemerges postnatally in a subpopulation of large-diameter GG neurons expressing the mechanoreceptor marker NF200 and the GDNF coreceptor GFRα1. Intriguingly, we observed that ablation of these neurons in adult Ret-Cre/ERT2; Rosa26LSL-DTA mice caused a specific loss of tactile, but not chemical or thermal, electrophysiological responses. Overall, the GDNF-Ret pathway exerts two critical and distinct functions in the peripheral taste system: embryonic chemosensory cell fate determination and the specification of lingual mechanoreceptors.


Subject(s)
Cell Differentiation/physiology , Chemoreceptor Cells/physiology , Gene Expression Regulation, Developmental/drug effects , Glial Cell Line-Derived Neurotrophic Factor/metabolism , Proto-Oncogene Proteins c-ret/metabolism , Taste/physiology , Animals , Geniculate Ganglion , Glial Cell Line-Derived Neurotrophic Factor/genetics , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Mice , Mice, Knockout , Protein-Tyrosine Kinases/genetics , Protein-Tyrosine Kinases/metabolism , Proto-Oncogene Proteins c-ret/genetics , Pyrazoles/pharmacology , Pyrimidines/pharmacology , RNA, Untranslated/genetics , RNA, Untranslated/metabolism , Signal Transduction , Tamoxifen , Temperature , Tongue/innervation , Touch , Transcription Factor Brn-3A , Transcription Factors/genetics , Transcription Factors/metabolism
11.
Surg Radiol Anat ; 43(2): 243-250, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32960308

ABSTRACT

PURPOSE: Fibers of the glossopharyngeal part of the superior constrictor muscle are connected with fibers of the transverse lingual muscle, forming a ring of muscle at the base of the tongue. This group of muscles constrict the midpharyngeal cavity during retrusive movement of the tongue. The purpose of this study is to identify the contribution of the lingual branch of the glossopharyngeal nerve to the neuro-motor control of three muscles: the glossopharyngeal part of the superior pharyngeal constrictor muscle, the palatopharyngeal and the palatoglossus muscles. METHODS: Six en bloc samples (9 sides), including the tissue from the skull base to the hyoid bone were obtained from adult human cadavers. Nerve fiber of the lingual branch of the glossopharyngeal nerve (main root of the glossopharyngeal nerve) was examined by the use of a binocular stereomicroscope. RESULTS: We observed that, after branching to the stylopharyngeal muscle, the lingual branch of the glossopharyngeal nerve branched to the glossopharyngeal part of the superior pharyngeal constrictor muscle, the palatopharyngeal and the palatoglossus muscles before inserting into the space between the muscle layers of the superior and middle pharyngeal constrictors. CONCLUSION: These neuromuscular arrangements may suggest the presence of specialized constrictive movements of the midpharygeal cavity at the level of the base of the tongue with the retrusive movement of the tongue. The simultaneous contraction of the palatopharyngeal and palatoglossus muscles on the pharyngeal stage of deglutition may aid in the passage of bolus from the oral cavity to the midpharyngeal cavity by increasing pharyngeal pressure.


Subject(s)
Glossopharyngeal Nerve/anatomy & histology , Nerve Fibers , Pharyngeal Muscles/innervation , Tongue/innervation , Adult , Deglutition/physiology , Humans , Muscle Contraction/physiology , Pharyngeal Muscles/physiology , Tongue/physiology
12.
Proc Natl Acad Sci U S A ; 114(48): E10369-E10378, 2017 11 28.
Article in English | MEDLINE | ID: mdl-29133390

ABSTRACT

Striking taste disturbances are reported in cancer patients treated with Hedgehog (HH)-pathway inhibitor drugs, including sonidegib (LDE225), which block the HH pathway effector Smoothened (SMO). We tested the potential for molecular, cellular, and functional recovery in mice from the severe disruption of taste-organ biology and taste sensation that follows HH/SMO signaling inhibition. Sonidegib treatment led to rapid loss of taste buds (TB) in both fungiform and circumvallate papillae, including disruption of TB progenitor-cell proliferation and differentiation. Effects were selective, sparing nontaste papillae. To confirm that taste-organ effects of sonidegib treatment result from HH/SMO signaling inhibition, we studied mice with conditional global or epithelium-specific Smo deletions and observed similar effects. During sonidegib treatment, chorda tympani nerve responses to lingual chemical stimulation were maintained at 10 d but were eliminated after 16 d, associated with nearly complete TB loss. Notably, responses to tactile or cold stimulus modalities were retained. Further, innervation, which was maintained in the papilla core throughout treatment, was not sufficient to sustain TB during HH/SMO inhibition. Importantly, treatment cessation led to rapid and complete restoration of taste responses within 14 d associated with morphologic recovery in about 55% of TB. However, although taste nerve responses were sustained, TB were not restored in all fungiform papillae even with prolonged recovery for several months. This study establishes a physiologic, selective requirement for HH/SMO signaling in taste homeostasis that includes potential for sensory restoration and can explain the temporal recovery after taste dysgeusia in patients treated with HH/SMO inhibitors.


Subject(s)
Antineoplastic Agents/adverse effects , Biphenyl Compounds/adverse effects , Dysgeusia/physiopathology , Pyridines/adverse effects , Signal Transduction/drug effects , Taste/drug effects , Tongue/physiopathology , Animals , Carcinoma, Basal Cell/drug therapy , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Chorda Tympani Nerve/drug effects , Chorda Tympani Nerve/physiopathology , Disease Models, Animal , Dysgeusia/chemically induced , Dysgeusia/pathology , Hedgehog Proteins/antagonists & inhibitors , Hedgehog Proteins/metabolism , Humans , Mice , Mice, Inbred C57BL , Mice, Knockout , Recovery of Function , Skin Neoplasms/drug therapy , Smoothened Receptor/antagonists & inhibitors , Smoothened Receptor/genetics , Smoothened Receptor/metabolism , Stem Cells/drug effects , Taste/physiology , Taste Buds/cytology , Taste Buds/drug effects , Taste Buds/pathology , Taste Buds/physiopathology , Tongue/drug effects , Tongue/innervation
13.
J Stroke Cerebrovasc Dis ; 29(2): 104459, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31839548

ABSTRACT

A 51-year-old Japanese woman was admitted to our hospital because of speech difficulty following severe headache. Neurological examination showed dysarthria and tongue weakness on the right side, indicating right hypoglossal nerve palsy. Needle electromyography of the right side of the tongue showed fibrillation potentials. Magnetic resonance angiography and computed tomography angiography revealed a right, persistent, primitive hypoglossal artery (PPHA) that met Lie's diagnostic criteria. Digital subtraction angiography showed an extended PPHA with irregular caliber in the portion running through the right hypoglossal canal. We diagnosed compression neuropathy of the hypoglossal nerve due to PPHA enlargement based on the findings of ipsilateral hypoglossal nerve palsy, fibrillation that indicated peripheral nerve palsy, and the enlarged diameter of the portion of the PPHA running through the right hypoglossal canal. We prescribed antihypertensive therapy. At 1 year after onset, her tongue weakness was alleviated. Clinicians should consider compression neuropathy due to a PPHA as one of the possibilities in the differential diagnosis of hypoglossal nerve palsy.


Subject(s)
Arteries/abnormalities , Hypoglossal Nerve Diseases/etiology , Hypoglossal Nerve/physiopathology , Nerve Compression Syndromes/etiology , Tongue/blood supply , Tongue/innervation , Vascular Malformations/complications , Antihypertensive Agents/therapeutic use , Arteries/diagnostic imaging , Arteries/physiopathology , Female , Humans , Hypoglossal Nerve Diseases/diagnosis , Hypoglossal Nerve Diseases/physiopathology , Middle Aged , Nerve Compression Syndromes/diagnosis , Nerve Compression Syndromes/physiopathology , Recovery of Function , Treatment Outcome , Vascular Malformations/diagnostic imaging , Vascular Malformations/drug therapy , Vascular Malformations/physiopathology
14.
J Neuroradiol ; 47(2): 136-150, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31034896

ABSTRACT

The hypoglossal nerve gives motor innervation to the intrinsic and extrinsic muscles of the tongue. Pathology of this nerve affects the balanced action of the genioglossus muscle causing tongue deviation toward the weak side. Clinically, hypoglossal nerve palsy manifests with difficulty chewing, swallowing and with dysarthric speech herein, we review the anatomy of the hypoglossal nerve as well as common and infrequent lesions that can affect this nerve along its course.


Subject(s)
Brain Neoplasms/complications , Hypoglossal Nerve Diseases/diagnostic imaging , Hypoglossal Nerve Diseases/pathology , Skull Neoplasms/complications , Brain Stem Neoplasms/diagnostic imaging , Brain Stem Neoplasms/pathology , Glioma/diagnostic imaging , Glioma/pathology , Humans , Hypoglossal Nerve Diseases/etiology , Meningeal Neoplasms/complications , Meningeal Neoplasms/diagnostic imaging , Meningeal Neoplasms/pathology , Meningioma/complications , Meningioma/diagnostic imaging , Meningioma/pathology , Skull Neoplasms/pathology , Tongue/innervation
15.
Anaesthesist ; 69(9): 649-652, 2020 09.
Article in German | MEDLINE | ID: mdl-32591840

ABSTRACT

A 42-year-old female patient suffered an infranuclear hypoglossal nerve paresis with right-sided swelling and weakness of the tongue following a short duration mask anesthesia for a follicle puncture. This resulted in dysarthria and dysphagia persisting for more than 3 months. A return to work was initially impossible. Etiopathogenetically, a mechanical compression of the peripheral hypoglossal nerve by positioning or reclination during mask ventilation is discussed. Conclusion for clinical practice: In order to protect against lesions of the hypoglossal nerve, the pre-anaesthesiological examination should ask specifically about cervical problems as an indication of individual sensitivity to reclination. In such cases, special attention should be paid to careful patient positioning. Even shorter periods of reclination or compression of the soft tissues of the neck can result in lesions, therefore tolls such as a Wendl or Guedel tube should be used accordingly.


Subject(s)
Anesthesia, General/adverse effects , Hypoglossal Nerve Diseases/etiology , Intubation, Intratracheal/adverse effects , Adult , Deglutition Disorders , Dysarthria , Female , Humans , Tongue/innervation
16.
J Neurosci ; 38(31): 6873-6887, 2018 08 01.
Article in English | MEDLINE | ID: mdl-29954852

ABSTRACT

The rodent peripheral gustatory system is especially plastic during early postnatal development and maintains significant anatomical plasticity into adulthood. Thus, taste information carried from the tongue to the brain is built and maintained on a background of anatomical circuits that have the capacity to change throughout the animal's lifespan. Recently, the neurotrophin brain-derived neurotrophic factor (BDNF) was shown to be required in the tongue to maintain normal levels of innervation in taste buds at adulthood, indicating that BDNF is a key molecule in the maintenance of nerve/target matching in taste buds. Here, we tested whether maintenance of the central process of these gustatory nerves at adulthood also relies on BDNF by using male and female transgenic mice with inducible CreERT2 under the control of the keratin 14 promoter or under control of the ubiquitin promoter to remove Bdnf from the tongue or from all tissues, respectively. We found that the terminal fields of gustatory nerves in the nucleus of the solitary tract were expanded when Bdnf was removed from the tongue at adulthood and with even larger and more widespread changes in mice where Bdnf was removed from all tissues. Removal of Bdnf did not affect numbers of ganglion cells that made up the nerves and did not affect peripheral, whole-nerve taste responses. We conclude that normal expression of Bdnf in gustatory structures is required to maintain normal levels of innervation at adulthood and that the central effects of Bdnf removal are opposite of those in the tongue.SIGNIFICANCE STATEMENT BDNF plays a major role in the development and maintenance of proper innervation of taste buds. However, the importance of BDNF in maintaining innervation patterns of gustatory nerves into central targets has not been assessed. Here, we tested whether Bdnf removal from the tongue or from all structures in adult mice impacts the maintenance of how taste nerves project to the first central relay. Deletion of Bdnf from the tongue and from all tissues led to a progressively greater expansion of terminal fields. This demonstrates, for the first time, that BDNF is necessary for the normal maintenance of central gustatory circuits at adulthood and further highlights a level of plasticity not seen in other sensory system subcortical circuits.


Subject(s)
Brain-Derived Neurotrophic Factor/physiology , Solitary Nucleus/pathology , Taste Buds/metabolism , Taste/physiology , Tongue/innervation , Animals , Axons/ultrastructure , Cell Count , Female , Geniculate Ganglion/metabolism , Geniculate Ganglion/ultrastructure , Keratin-14/genetics , Male , Mice , Mice, Knockout , Mice, Transgenic , Organ Specificity , Promoter Regions, Genetic , Recombinant Proteins/metabolism , Solitary Nucleus/metabolism , Taste Buds/ultrastructure , Ubiquitin/genetics
17.
J Neurophysiol ; 122(5): 2054-2060, 2019 11 01.
Article in English | MEDLINE | ID: mdl-31533009

ABSTRACT

The mammalian tongue contains eight muscles that collaborate to ensure that suckling, swallowing, and other critical functions are robust and reliable. Seven of the eight tongue muscles are innervated by hypoglossal motoneurons (XIIMNs). A somatotopic organization of the XII motor nucleus, defined in part by the mechanical action of a neuron's target muscle, has been described, but whether or not XIIMNs within a compartment are functionally specialized is unsettled. We hypothesize that developing XIIMNs are assigned unique functional properties that reflect the challenges that their target muscle faces upon the transition from in utero to terrestrial life. To address this, we studied XIIMNs that innervate intrinsic and extrinsic tongue muscles, because intrinsic muscles play a more prominent role in suckling than the extrinsic muscles. We injected dextran-rhodamine into the intrinsic longitudinal muscles (IL) and the extrinsic genioglossus, and physiologically characterized the labeled XIIMNs. Consistent with earlier work, IL XIIMNs (n = 150) were located more dorsally within the nucleus, and GG XIIMNs (n = 55) more ventrally. Whole cell recordings showed that resting membrane potential was, on average, 9 mV more depolarized in IL than in GG XIIMNs (P = 0.0019), and the firing threshold in response to current injection was lower in IL (-31 ± 23 pA) than in GG XIIMNs (225 ± 39 pA; P < 0.0001). We also found that the appearance of net outward currents in GG XIIMNs occurred at more hyperpolarized membrane potentials than IL XIIMNs, consistent with lower excitability in GG XIIMNs. These observations document muscle-specific functional specializations among XIIMNs.NEW & NOTEWORTHY The hypoglossal motor nucleus contains motoneurons responsible for innervating one of seven different muscles with notably different biomechanics and patterns of use. Whether or not motoneurons innervating the different muscles also have unique functional properties (e.g., spiking behavior, synaptic physiology) is poorly understood. In this work we show that neonatal hypoglossal motoneurons innervating muscles that shape the tongue (intrinsic longitudinal muscles) have different electrical properties than those innervating the genioglossus, which controls tongue position.


Subject(s)
Electrophysiological Phenomena/physiology , Hypoglossal Nerve/physiology , Medulla Oblongata/physiology , Motor Neurons/physiology , Muscle, Skeletal/physiology , Musculoskeletal Physiological Phenomena , Tongue/innervation , Animals , Animals, Newborn , Female , Male , Membrane Potentials/physiology , Patch-Clamp Techniques , Rats , Rats, Sprague-Dawley
18.
Sleep Breath ; 23(1): 235-241, 2019 Mar.
Article in English | MEDLINE | ID: mdl-29956103

ABSTRACT

OBJECTIVE: Selective upper airway stimulation (sUAS) is a new treatment modality for patients with obstructive sleep apnea (OSA) and continuous positive airway pressure (CPAP) failure. The aim of this study was to analyze therapy adherence and to structure patient experience reports. METHODS: Patients from two German implantation centers were included. Besides demographic and OSA characteristics of that cohort, patients answered a questionnaire on subjective sensation of the stimulation, use of different functions, side effects, and an inventory for the description of the attitude towards sUAS. The use of the sUAS was evaluated as a read-out of the implanted system. RESULTS: The overall apnea-hypopnea-index (AHI) of that 102 assessed patients reduced from initially 32.8/h to 12.6/h at the last available assessment. The responder rate was 75%. There was an objective therapy usage of 5.7 h and subjective reports of 6.8 nights per week. The attitude resulted in strong agreement towards the statement "UAS reduces the problems caused by my sleep apnea". Information on sensing the stimulation and usage habits could be gathered such as that stimulation is only sensed by 67.9% of the patients upon waking in the morning and that 73.6% of the patients do not change the voltage in general. CONCLUSION: This investigation on the sUAS therapy revealed a high adherence to the therapy. The AHI or daytime sleepiness do not have obvious influence on adherence. Patients expressed a positive attitude towards sUAS. These patient reports upon stimulation experiences are of great help to consult candidates for sUAS in future.


Subject(s)
Continuous Positive Airway Pressure , Electric Stimulation Therapy/methods , Hypoglossal Nerve/physiopathology , Patient Compliance , Patient Satisfaction , Sleep Apnea, Obstructive/therapy , Adult , Aged , Combined Modality Therapy , Electric Stimulation Therapy/adverse effects , Electric Stimulation Therapy/instrumentation , Female , Follow-Up Studies , Humans , Male , Middle Aged , Polysomnography , Prostheses and Implants , Sleep Apnea, Obstructive/physiopathology , Surveys and Questionnaires , Tongue/innervation , Treatment Outcome
19.
J Craniofac Surg ; 30(2): e101-e106, 2019.
Article in English | MEDLINE | ID: mdl-30507882

ABSTRACT

INTRODUCTION: Minimally invasive transoral surgery for oropharyngeal cancer is a challenge for head and neck surgeons because of the inside-out anatomic presentation and the confined workspace. This study was performed to describe the main neurovascular and muscular landmarks in a transoral approach. The authors propose an anatomic stratification for this surgery. MATERIALS AND METHODS: Lateral wall of the oropharynx and base of the tongue of 15 formalin-fixed heads (30 sides) and 5 fresh cadaveric heads (10 sides) sagittal sectioned were dissected from the inside outwards. Dissection of 7 fresh cadaveric heads via an endoscopic transoral approach was also performed. RESULTS: The lateral oropharyngeal wall was divided into 3 layers from medial to lateral, based in the styloid muscle diaphragm. The first layer, medial to styloid muscles, includes the tonsillar vascularization and the lingual branch of the glossopharyngeal nerve. The second layer, lateral to constrictor muscles, includes the pharyngeal venous plexus, the glossopharyngeal nerve, and the lingual artery. The third layer, lateral to styloid diaphragm, includes the parapharyngeal and submandibular spaces, the carotid vessels and lingual, vagus, glossopharyngeal and hypoglossal nerves. The base of the tongue was divided into central and lateral parts, which contain the lingual artery and lingual branches of the glossopharyngeal nerve. The main landmarks to find the neurovascular structures in each layer are described. CONCLUSION: The authors propose an anatomic division, which helps to plan oropharynx and base of the tongue surgery. This anatomic stratification is useful to surgeons when performing a reconstruction of the oropharynx with a transoral approach.


Subject(s)
Glossopharyngeal Nerve/anatomy & histology , Hypoglossal Nerve/anatomy & histology , Oropharynx , Otorhinolaryngologic Surgical Procedures/methods , Tongue , Anatomic Landmarks , Arteries/anatomy & histology , Cadaver , Humans , Models, Anatomic , Oropharynx/anatomy & histology , Oropharynx/innervation , Oropharynx/surgery , Tongue/anatomy & histology , Tongue/innervation , Tongue/surgery
20.
Clin Anat ; 32(5): 635-641, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30815909

ABSTRACT

The purpose of this research is to obtain morphological information about the traveling route, branching pattern, and distribution within the tongue of the lingual nerve, all of which are important for oral surgical procedures. Using 20 sides from 10 Japanese cadaveric heads, we followed the lingual nerve from its merging point with the chorda tympani to its peripheral terminal in the tongue. We focused on the collateral branches in the area before reaching the tongue and the communication between the lingual and hypoglossal nerves reaching the tongue. The collateral branches of the lingual nerve were distributed in the oral mucosa between the palatoglossal arch and the mandibular molar region. Two to eight collateral branches arose from the main trunk of the nerve, and the configuration of branching was classified into three types. More distally, the lingual nerve started to communicate with the hypoglossal nerve before passing the anterior border of the hyoglossus muscle. Nerve communications were also found in the main body and near the apex of the tongue. A thorough understanding of the collateral branches near the tongue, and the communication with the hypoglossal nerve inside the tongue, will help to prevent functional disorders from local anesthesia and oral surgical procedures associated with the lingual nerve. Clin. Anat. 32:635-641, 2019. © 2019 Wiley Periodicals, Inc.


Subject(s)
Lingual Nerve/anatomy & histology , Tongue/innervation , Cadaver , Female , Humans , Hypoglossal Nerve/anatomy & histology , Male , Oral Surgical Procedures
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