Taste Papillae Research Articles

The c-kit Receptor Tyrosine Kinase Marks Sweet or Umami Sensing T1R3 Positive Adult Taste Cells in Mice

Previous studies have described a number of protein tyrosine kinases (epidermal growth factor receptor, ErbB2, ErbB3, and c-kit) to be expressed in taste bud cells, their innervating nerves, and in developing taste papillae. Immunohistochemical staining of mouse taste buds was performed to characterize the expression patterns of the c-kit receptor in taste. Here we demonstrate that c-kit positive cells are exclusively co-localized with T1R3 (which forms one half of the receptors for sweet and umami taste) in adult taste cells. This implies that c-kit+ cells are primarily taste cells that respond to sweet and umami, but not to bitter, sour, or salty. These data indicate that the control of c-kit activation may be important for proper taste bud formation and may aid in the maintenance of this specific mature taste cell subpopulation. Further characterization of the functional role of c-kit in taste may lead to superior taste cell cultures or organoids, and elucidate mechanisms of taste cell regulation.

Role of FGF10/FGFR2b Signaling in Mouse Digestive Tract Development, Repair and Regeneration Following Injury.

During embryonic development, the rudimentary digestive tract is initially a tube-like structure. It is composed of epithelial cells surrounded by mesenchymal cells. Reciprocal epithelial–mesenchymal interactions progressively subdivide this primitive tube into distinct functional regions: the tongue, the pharynx, the esophagus, the stomach, the duodenum, the small intestine, the cecum, the large intestine, the colon, and the anus as well as the pancreas and the liver. Fibroblast growth factors (Fgfs) constitute a family of conserved small proteins playing crucial roles during organogenesis, homeostasis, and repair after injury. Among them, fibroblast growth factor 10 (Fgf10) has been reported to orchestrate epithelial–mesenchymal interactions during digestive tract development. In mice, loss of function of Fgf10 as well as its receptor fibroblast growth factor receptor 2b (Fgfr2b) lead to defective taste papillae in the tongue, underdeveloped and defective differentiation of the stomach, duodenal, cecal, and colonic atresias, anorectal malformation, as well as underdeveloped pancreas and liver. Fgf signaling through Fgfr2b receptor is also critical for the repair process after gut injury. In the adult mice, a malabsorption disorder called small bowel syndrome is triggered after massive small bowel resection (SBR). In wild-type mice, SBR leads to a regenerative process called gut adaptation characterized by an increase in the diameter of the remaining small intestine as well as by the presence of deeper crypts and longer villi, altogether leading to increased intestinal surface. Intestinal stem cells are key for this regeneration process. Induction of Fgf10 expression in the Paneth cells located in the crypt following SBR suggests a critical role for this growth factor in the process of gut adaptation.

The prospective role of mesenchymal stem cells exosomes on circumvallate taste buds in induced Alzheimer’s disease of ovariectomized albino rats: (Light and transmission electron microscopic study)

ObjectiveTo elucidate the effect of Alzheimer’s disease on the structure of circumvallate papilla taste buds and the possible role of exosomes on the taste buds in Alzheimer’s disease. DesignForty two ovariectomized female adult albino rats were utilized and divided into: Group I: received vehicle. Group II: received aluminum chloride to induce Alzheimer’s disease. Group III: after the induction of Alzheimer’s disease, each rat received single dose of exosomes then left for 4 weeks. The circumvallate papillae were prepared for examination by light and transmission electron microscope. Statistical analysis: histomorphometric data were statistically analyzed. ResultsHistological examination of circumvallate papilla in Group I showed normal histological features. Group II revealed distorted features. Group III illustrated nearly normal histological features of circumvallate. Silver impregnation results showed apparently great number of heavily impregnated glossopharyngeal nerve fibers in both Groups I & III but markedly decreased in Group II. Synaptophysin-immunoreactivity was strong in Group I, mild in Group II and moderate in Group III. The ultra-structural examination of taste bud cells revealed normal features in Group I, distorted features in Group II and almost normal features in Group III. Statistically highest mean of Synaptophysin-immunoreactivity area% was for Group I, followed by Group III, and the least value was for Group II. ConclusionsAlzheimer’s disease has degenerative effects. Bone marrow mesenchymal stem cell (BM-MSC)-derived exosomes have the ability to improve the destructive changes induced by Alzheimer’s disease.

Increased activity of mesenchymal ALK2-BMP signaling causes posteriorly truncated microglossia and disorganization of lingual tissues.

Proper development of taste organs including the tongue and taste papillae requires interactions with the underlying mesenchyme through multiple molecular signaling pathways. The effects of bone morphogenetic proteins (BMPs) and antagonists are profound, however, the tissue-specific roles of distinct receptors are largely unknown. Here, we report that constitutive activation (ca) of ALK2-BMP signaling in the tongue mesenchyme (marked by Wnt1-Cre) caused microglossia-a dramatically smaller and misshapen tongue with a progressively severe reduction in size along the anteroposterior axis and absence of a pharyngeal region. At E10.5, the tongue primordia (branchial arches 1-4) formed in Wnt1-Cre/caAlk2 mutants while each branchial arch responded to elevated BMP signaling distinctly in gene expression of BMP targets (Id1, Snai1, Snai2, and Runx2), proliferation (Cyclin-D1) and apoptosis (p53). Moreover, elevated ALK2-BMP signaling in the mesenchyme resulted in apparent defects of lingual epithelium, muscles, and nerves. In Wnt1-Cre/caAlk2 mutants, a circumvallate papilla was missing and further development of formed fungiform papillae was arrested in late embryos. Our data collectively demonstrate that ALK2-BMP signaling in the mesenchyme plays essential roles in orchestrating various tissues for proper development of the tongue and its appendages in a region-specific manner.

Taste loss with obesity in mice and men

Our sense of taste is critical in defining our food choices and habits. Located primarily in our tongue, taste buds are small assemblies of constantly renewing sensory cells, tasked with evaluating oral stimuli before the food we eat is consumed. Using both mice and a free-living human population, we tracked taste papilla abundancy with weight gain, to test for deficiencies in the taste system of obese mice and humans with increased adiposity. Mice fed a high-fat diet for 8 weeks expressed markers for all subtypes of taste cells at a lower level than chow-fed counterparts. This came alongside the loss of markers for taste cell proliferation (Ki-67) and development (β-catenin), as well as lower fungiform papillae density, consistent with earlier results showing lower circumvallate taste bud abundance in obese mice. Likewise, in a population of college students tracked through 4 years of college attendance, the change in density of fungiform papillae, which house taste buds in the anterior tongue, was negatively correlated with change in neck circumference, a marker of adiposity. These results highlight changes in taste during weight gain as a potentially important consideration in the study of obesity.

Expression of Oncofetal Antigen 5T4 in Murine Taste Papillae.

Background: Multicellular taste buds located within taste papillae on the tongue mediate taste sensation. In taste papillae, taste bud cells (TBCs), such as taste receptor cells and taste precursor cells, and the surrounding lingual epithelium including epithelial progenitors (also called taste stem/progenitor cells) are maintained by continuous cell turnover throughout life. However, it remains unknown how the cells constituting taste buds proliferate and differentiate to maintain taste bud tissue. Based on in situ hybridization (ISH) screening, we demonstrated that the oncofetal antigen 5T4 (also known as trophoblast glycoprotein: TPBG) gene is expressed in the adult mouse tongue.Results: In immunohistochemistry of coronal tongue sections, 5T4 protein was detected at a low level exclusively in the basal part of the lingual epithelium in developing and adult mice, and at a high level particularly in foliate papillae and circumvallate papillae (CVPs). Furthermore, immunohistochemistry of the basal part of CVPs indicated that the proliferation marker PCNA (proliferating cell nuclear antigen) co-localized with 5T4. 5T4 was strongly expressed in Krt5+ epithelial progenitors and Shh+ taste precursor cells, but weakly in mature taste receptor cells. The number of proliferating cells in the CVP was higher in 5T4-knockout mice than in wild-type (WT) mice, while neither cell differentiation nor the size of taste buds differed between these two groups of mice. Notably, X-ray irradiation enhanced cell proliferation more in 5T4-knockout mice than in WT mice.Conclusion: Our results suggest that 5T4, expressed in epithelial progenitors (taste stem/progenitor cells), and taste precursor cells, may influence the maintenance of taste papillae under both normal and injury conditions.

Early taste buds are from Shh+ epithelial cells of tongue primordium in distinction from mature taste bud cells which arise from surrounding tissue compartments

Mammalian taste buds emerge perinatally and most become mature 3–4 weeks after birth. Mature taste bud cells in rodents are known to be renewed by the surrounding K14+ basal epithelial cells and potentially other progenitor source(s), but the dynamics between initially developed taste buds and surrounding tissue compartments are unclear. Using the K14-Cre and Dermo1-Cre mouse lines to trace epithelial and mesenchymal cell lineages, we found that early taste buds in E18.5 and newborn mouse tongues are not derived from either lineage. At E11.5 when the tongue primordia (i.e., lingual swellings) emerge, the relatively homogeneous sonic hedgehog-expressing (Shh+) epithelial cells express Keratin (K) 8, a marker that is widely used to label taste buds. Mapping lineage of E11.0 Shh+ epithelium of the tongue rudiment with Shh-CreERT2/RFP mice demonstrated that both the early taste buds and the surrounding lingual epithelium are from the same population of progenitors – Shh+ epithelial cells of the tongue primordium. In combination with previous reports, we propose that Shh+K8+ cells in the homogeneous epithelium of tongue primordium at early embryonic stages are programmed to become taste papilla and taste bud cells. Switching off Shh and K8 expression in the Shh+ epithelial cells of the tongue primordium transforms the cells to non-gustatory cells surrounding papillae, including K14+ basal epithelial cells which will eventually contribute to the cell renewal of mature taste buds.

Mammalian Taste Cells Express Functional Olfactory Receptors.

The peripheral taste and olfactory systems in mammals are separate and independent sensory systems. In the current model of chemosensation, gustatory, and olfactory receptors are genetically divergent families expressed in anatomically distinct locations that project to disparate downstream targets. Although information from the 2 sensory systems merges to form the perception of flavor, the first cross talk is thought to occur centrally, in the insular cortex. Recent studies have shown that gustatory and olfactory receptors are expressed throughout the body and serve as chemical sensors in multiple tissues. Olfactory receptor cDNA has been detected in the tongue, yet the presence of physiologically functional olfactory receptors in taste cells has not yet been demonstrated. Here we report that olfactory receptors are functionally expressed in taste papillae. We found expression of olfactory receptors in the taste papillae of green fluorescent protein-expressing transgenic mice and, using immunocytochemistry and real-time quantitative polymerase chain reaction experiments, the presence of olfactory signal transduction molecules and olfactory receptors in cultured human fungiform taste papilla (HBO) cells. Both HBO cells and mouse taste papilla cells responded to odorants. Knockdown of adenylyl cyclase mRNA by specific small inhibitory RNA and pharmacological block of adenylyl cyclase eliminated these responses, leading us to hypothesize that the gustatory system may receive olfactory information in the periphery. These results provide the first direct evidence of the presence of functional olfactory receptors in mammalian taste cells. Our results also demonstrate that the initial integration of gustatory and olfactory information may occur as early as the taste receptor cells.

Hedgehog Signaling Regulates Taste Organs and Oral Sensation: Distinctive Roles in the Epithelium, Stroma, and Innervation.

The Hedgehog (Hh) pathway has regulatory roles in maintaining and restoring lingual taste organs, the papillae and taste buds, and taste sensation. Taste buds and taste nerve responses are eliminated if Hh signaling is genetically suppressed or pharmacologically inhibited, but regeneration can occur if signaling is reactivated within the lingual epithelium. Whereas Hh pathway disruption alters taste sensation, tactile and cold responses remain intact, indicating that Hh signaling is modality-specific in regulation of tongue sensation. However, although Hh regulation is essential in taste, the basic biology of pathway controls is not fully understood. With recent demonstrations that sonic hedgehog (Shh) is within both taste buds and the innervating ganglion neurons/nerve fibers, it is compelling to consider Hh signaling throughout the tongue and taste organ cell and tissue compartments. Distinctive signaling centers and niches are reviewed in taste papilla epithelium, taste buds, basal lamina, fibroblasts and lamellipodia, lingual nerves, and sensory ganglia. Several new roles for the innervation in lingual Hh signaling are proposed. Hh signaling within the lingual epithelium and an intact innervation each is necessary, but only together are sufficient to sustain and restore taste buds. Importantly, patients who use Hh pathway inhibiting drugs confront an altered chemosensory world with loss of taste buds and taste responses, intact lingual touch and cold sensation, and taste recovery after drug discontinuation.

Sophorolipid Biosurfactants Activate Taste Receptor Type 1 Member 3‐Mediated Taste Responses and Block Responses to Bitter Taste In Vitro and In Vivo

AbstractSophorolipids (SL) are typically produced and secreted by select nonpathogenic yeast species (i.e., Candida) from renewable substrates. They are currently being used by industry on a limited basis in formulations for cleaning solutions as well as laundry and dishwashing detergents. Due to the nature of their chemical structure, it was hypothesized that SL would demonstrate taste‐sensory properties. In this study, SL were produced via fermentation on a mixed substrate platform with glucose and either palmitic acid, stearic acid, or oleic acid using Candida (currently reclassified as Starmerella) bombicola ATCC 22214. The taste properties of SL were determined using a single‐cell manual calcium imaging technique on cultured human fungiform taste papillae (HBO) cells. The results of those studies demonstrated that sweetener‐responsive HBO cells also respond to SL, and these responses are mediated by the type 1 taste receptors 3 (T1R3), because they were blocked by lactisole (a T1R3 receptor‐specific blocker). The involvement of the T1R3 receptor in SL recognition was confirmed via the chorda tympani nerve recording (CTNR) study in a (−/−) T1R3 knockout (KO) mouse model. We further demonstrated that SL are capable of blocking the bitter stimuli‐elicited responses both in HBO cells and in the CTNR study. This is the first report demonstrating that SL have taste‐sensory properties, which opens up numerous possibilities for practical applications of SL to ameliorate bitter tastes in foods and drugs and understand the potential source of dysgeusia in some patients.

Obesity is associated with altered gene expression in human tastebuds.

The role of taste perception in the development and persistence of obesity is currently unclear due to conflicting results from psychophysical and other studies. No study to date has assessed whether there is an underlying fundamental difference in the physiology of taste tissue between lean and obese individuals. We analysed the transcriptomic profile (RNA-seq) of human fungiform taste papillae biopsied from lean (n = 23) and obese (n = 13) Caucasian females (age range 18-55) to identify differences in gene expression. Obesity status was the major contributor to variance in global gene expression between individuals. A total of 62 genes had significantly different gene expression levels between lean and obese (P < 0.0002), with the specific taste associated genes phospholipase C beta 2 (PLCβ2) and sonic hedge-hog (SHH) having significantly reduced expression in obese group. Genes associated with inflammation and immune response were the top enriched biological pathways differing between the lean and the obese groups. Analysis of a broader gene set having a twofold change in expression (2619 genes) identified three enriched theme groups (sensory perception, cell and synaptic signalling, and immune response). Further, analysis of taste associated genes identified a consistent reduction in the expression of taste-related genes (in particular reduced type II taste cell genes) in the obese compared to the lean group. The findings show obesity is associated with altered gene expression in tastebuds. Furthermore, the results suggest the tastebud microenvironment is distinctly different between lean and obese persons and, that changes in sensory gene expression contribute to this altered microenvironment. This research provides new evidence of a link between obesity and altered taste and in the future may help design strategies to combat obesity.

SU55 - FETAL ALCOHOL EXPOSURE IN RATS LEADS TO LONG-TERM CHANGES IN DNA METHYLATION PATTERNS OF TASTE-RELATED GENES IN POSTNATAL TONGUE

Background Considerable evidence indicates that there are potential long-term consequences of maternal alcohol consumption. Such exposures can lead to postnatal changes in the formation and function of brain circuits involved in learning, memory, and reward processing, and increase subsequent risks of alcohol abuse in later life. Although much interest has focused on the central areas affected by such exposures, less attention has been paid to the effects such exposures produce in the peripheral gustatory system. Here, we studied the potential molecular adaptations produced by fetal alcohol exposure in the postnatal chemosensory system by studying DNA methylation changes in Circumvallate Papillae (CV) taste cells in postnatal rats. Methods Pregnant Long Evans rats were divided into two weight-matched groups. Within each group the dams were randomly assigned to one of two dietary treatments (ET: ethanol, FCL: free choice liquid). Dams in the ET group were given ad libitum access to a liquid ethanol containing diet, with increasing amounts of ethanol between gestational (G) days 6–10, and full strength dose during G11-20. In the full strength diet, ethanol provided 35% of an animal's daily calories. Moreover, the timing of these administrations also exposed the fetus to ethanol during the developmental period (G11–20) of olfactory and orosensory systems. After delivery, rats born to dams in the ET group or the FCL group were chosen at random and sacrificed during mid-adolescence at P42. DNA samples were isolated from the CV of tongues, followed by genome-wide differential methylation analysis using the Rat Methyl-Seq DMR Capture kit (Agilent) and Illumina NexteraXT sequencing protocol. Results Differentially methylated cytosine residues were observed within and at the promoter regions of a large amount of olfactory receptor, taste receptor, oral-irritation, and gustatory signal transduction genes. Detailed examination of the methylation patterns of oro-sensory genes revealed interesting features of alternation. We also tested the ability of Partial Least Squares Discriminant Analysis (PLS-DA) to identify specific cytosine residues that could separate the two groups of ET and FCL prenatal-exposed rats. This indicated that cytosine resides with the most distinguishing power appeared to be located in close proximity to each other, corroborating the Runs test results. Thus, prenatal ET exposure could lead to the formation of cis-acting methylation blocks that strongly regulate or coordinate the expression of chemosensory-related genes, and fundamentally alter taste perception and taste preferences. Furthermore, pathway analysis revealed enrichment of genes involved in signal transduction pathways and epigenetic modification pathways, including genes such as Grm3, S1pr1, Prkacb, Hdac7 and Kcnmb4. Discussion Our results are the first evidences indicating that in addition to central nerves system effects, fetal alcohol exposure induced alcohol preference in later life could also be produced by altered patterns of DNA methylation in the peripheral gustatory system, via dysregulated expression of oro-sensory-related genes.

Bones, Glands, Ears and More: The Multiple Roles of FGF10 in Craniofacial Development.

Members of the fibroblast growth factor (FGF) family have myriad functions during development of both non-vertebrate and vertebrate organisms. One of these family members, FGF10, is largely expressed in mesenchymal tissues and is essential for postnatal life because of its critical role in development of the craniofacial complex, as well as in lung branching. Here, we review the function of FGF10 in morphogenesis of craniofacial organs. Genetic mouse models have demonstrated that the dysregulation or absence of FGF10 function affects the process of palate closure, and FGF10 is also required for development of salivary and lacrimal glands, the inner ear, eye lids, tongue taste papillae, teeth, and skull bones. Importantly, mutations within the FGF10 locus have been described in connection with craniofacial malformations in humans. A detailed understanding of craniofacial defects caused by dysregulation of FGF10 and the precise mechanisms that underlie them offers new opportunities for development of medical treatments for patients with birth defects and for regenerative approaches for cancer patients with damaged gland tissues.

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.

Macroscopic and microscopic study of the tongue of the aardvark (Orycteropus afer, Orycteropodidae).

The aim of this study was to describe the morphology of the tongue in the aardvark (Orycteropus afer). The tongues from one adult and one three-week old aardvark females and one neonate aardvark were studied. The tongue was elongated in the adult and young aardvarks and had a triangular apex in the rostral part of the tongue. Its dorsal surface was covered by numerous papillae divided into mechanical papillae, present in the form of abundant conical or drop-like filiform papillae, and taste papillae in the form of numerous fungiform papillae and three vallate papillae arranged in a V-shape in the caudal part of the tongue (one papilla was located centrally and caudally with respect to the remaining two papillae). The vallate papillae were round with conical pseudopapillae on their surface. They were surrounded by an annular pad, which was formed by filiform papillae with conical tip. Numerous openings of barrel-shaped taste buds were present in the epithelium covering the surface of fungiform papillae, and in the epithelium of inner walls of the vallate papillae. The serous von Ebner`s glands were located beneath the vallate papillae. The mucoserous Weber`s glands were PAS, AB pH2.5, pH1.0 and AB/PAS positive and HDI-weakly positive.

Taste Exam: A Brief and Validated Test.

The emerging importance of taste in medicine and biomedical research, and new knowledge about its genetic underpinnings, has motivated us to supplement classic taste-testing methods in two ways. First, we explain how to do a brief assessment of the mouth, including the tongue, to ensure that taste papillae are present and to note evidence of relevant disease. Second, we draw on genetics to validate taste test data by comparing reports of perceived bitterness intensity and inborn receptor genotypes. Discordance between objective measures of genotype and subjective reports of taste experience can identify data collection errors, distracted subjects or those who have not understood or followed instructions. Our expectation is that fast and valid taste tests may persuade researchers and clinicians to assess taste regularly, making taste testing as common as testing for hearing and vision. Finally, because many tissues of the body express taste receptors, taste responses may provide a proxy for tissue sensitivity elsewhere in the body and, thereby, serve as a rapid, point-of-care test to guide diagnosis and a research tool to evaluate taste receptor protein function.

Ultrastructure of the tongue and histochemical features of the lingual salivary glands in buzzards

The macroscopic characteristics of the tongues of 8 long-legged buzzards are described and scanning electron microscopy was used to examine the epithelial tissue of the tongue?s surface. Crossman?s modified triple staining method and hematoxylin and eosin dye were used to determine the locations and general histological features of the lingual salivary glands. The nature of the glandular secretions was examined by staining with PAS, AB pH 1.0, AB pH 2.5, and PAS-AB pH 1.0 and pH 2.5, and diastase enzyme digestion. PAS staining and weak, moderate, and strong methylation procedures as well as sialidase and hyaluronidase applications were performed. We report the finding of focal accumulations of the anterior lingual salivary glands at the tongue?s base with numerous duct openings in this area. This finding, in conjunction with the absence of taste papillae in the tongue epithelium, suggests that the role of the tongue in buzzards is to mix food with saliva and to move the food bolus rapidly to the back of the oral cavity. The acidic secretions of the lingual salivary glands not only have antimicrobial effects but also facilitate the swallowing process and may influence the digestive process in the distal parts of the alimentary tract.

Tongue Cleaning Increases the Perceived Intensity of Salty Taste.

Tongue coating, which refers to a greyish white deposit on the tongue surface, often covers the taste papillae on the dorsal tongue surface, decreasing taste sensitivity. This study investigated whether mechanical removal of the tongue coating affected the intensity of salt taste perception. This cross-sectional single blind study included 90 subjects (29 males, 61 females) with a mean age of 45 years (range 25-70 years). The presence and the amount of coating on the six sextants of the tongue were scored using the Winkel Tongue Coating Index (WTCI); the 90 included subjects had total WTCI scores ≥ 3. The intensity of the salt taste was tested using a drop of prepared tomato soup applied to the middle of the dorsal surface of the tongue before and then after tongue cleaning. The salt taste intensity was measured using a general Labeled Magnitude Scale (gLMS). The mean salt taste intensity was significantly different (p value = 0.0002) after the intervention versus before it, with the taste intensity increasing after tongue cleaning. The results indicated that the salt taste intensity increased after removal of the tongue coating. This study indicates that tongue cleaning, a simple technique used for oral hygiene, may be an effective way to reduce excess salt intake. Tongue cleaning could help individuals adhere to the WHO recommendations on dietary salt intake.

Expression of N-cadherin and cell surface molecules in the taste buds of mouse circumvallate papillae

ObjectivesCadherins are a type of adhesion molecule involved in cell–cell recognition and morphogenesis. N-cadherin is predominantly expressed in the nervous system, and is localized at synapses, where it not only plays an adhesive role, but also participates in the regulation of synaptic function and plasticity. Taste cells within taste buds have a limited lifespan, and are replaced on a regular basis. However, little is known regarding the expression pattern of cadherins in taste bud cells. In this study, we examined whether taste bud cells in mouse taste papillae express N-cadherins, and if so, which cell type(s) the N-cadherins are found in. MethodsWe examined the expression of N-cadherins by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and in situ hybridization. ResultsRT-PCR results demonstrated that N-cadherins are expressed in the taste bud-containing epithelium of the circumvallate papilla in mice. Based on immunohistochemical analyses, N-cadherins were found to be expressed in a subset of taste bud cells of gustatory papillae. Double-labelling studies showed that N-cadherin co-localizes with α-gustducin, aromatic L-amino acid decarboxylase (AADC), carbonic anhydrase IV (CA4), and phospholipase C β2 (PLCβ2). ConclusionsOur study indicated that N-cadherins are expressed in type II and III taste cells. Taken together with results from previous studies, we propose that N-cadherins might play a functional role in the establishment of nerve terminal connections.

Differences in the Density of Fungiform Papillae and Composition of Saliva in Patients With Taste Disorders Compared to Healthy Controls.

This study investigated the relation of the fungiform taste papillae density and saliva composition with the taste perception of patients suffering from diagnosed taste disorders. For this purpose, 81 patients and 40 healthy subjects were included. Taste was measured by means of regional and whole mouth chemosensory tests, and electrogustometry. Olfaction was assessed using the Sniffin Sticks. Fungiform papillae were quantified using the "Denver Papillae Protocol for Objective Analysis of Fungiform Papillae". In addition, salivary parameters [flow rate, total proteins, catalase, total anti-oxidative capacity (TAC), carbonic anhydrase VI (caVI), and pH] were determined and the Beck Depression Inventory was administered. Patients showed less taste papillae compared to healthy subjects. The number of papillae correlated with total taste strip score and salivary flow rate. Regarding salivary parameters, the flow rate, protein concentration, and TAC of patients were higher compared to controls. In addition, salivary flow rate, protease, caVI, and catalase values correlated with the summed taste strip score. Regarding various taste disorders, salty-dysgeusia patients showed the lowest taste test scores compared to those with bitter or metal-dysgeusia. Olfactory function of patients was significantly worse compared to healthy controls. This difference was most pronounced for ageusia patients. Compared to controls, patients also exhibited higher depressive symptoms. The density of fungiform papillae seemed to be positively associated with taste perception. Furthermore, patients exhibited changes in saliva composition (higher salivary flow rate, increased protein concentration, proteolysis, and TAC) compared to controls indicating that assessment of saliva may be critical for the diagnostic procedure in taste disorders.