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Finger, T. E.

Publications and source records attributed to Finger, T. E..

7 recordsLinked to original sources

Taste dysfunction in Long COVID

AbstractPersistent taste dysfunction is frequently reported in individuals with post-acute sequelae of infection by SARS-CoV-2 (Long COVID). The mechanisms and pathological correlates underlying this taste dysfunction are unknown. This study investigates the underlying pathology in 28 non-hospitalized subjects diagnosed with COVID-19 and who experienced taste disturbances more than 12 months after testing positive for SARS-CoV-2. To objectively establish the nature of taste deficit, we used the WETT taste test, which quantifies the subjects ability to taste each of the five taste qualities: sweet, umami, bitter, sour, and salty. We then biopsied five to eight fungiform taste papillae (FP) in 20 of the 28 subjects. The FPs were analyzed histologically for overall taste bud structure and innervation, and by quantitative PCR (qPCR) for mRNA expression of markers for different taste receptor cells. Although all subjects had reported taste dysfunction, only three showed overall taste scores below the 10th percentile for a normal population adjusted for age and sex. However, 11 of the 28 subjects exhibited total loss of one or more taste qualities. Loss of PLC{beta}2-dependent taste qualities (sweet, umami, bitter) was significantly more common and was correlated with reduced expression of PLC{beta}2 and Tas1R3 mRNAs. Histological analysis revealed generally preserved taste bud structure and innervation, but with occasional disorganized taste buds and abnormal, isolated PLC{beta}2-positive cells in the epithelium. Our findings suggest long-term taste dysfunction after COVID-19 occurs rarely -- more frequently involving PLC{beta}2-dependent taste qualities -- but is not due to wholesale disruption of the taste periphery.

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Death in the taste bud: Morphological features of dying taste cells and engulfment by Type I cells

Taste buds comprise 50-100 epithelial derived cells, including glial-like cells (Type I) and two types of receptor cells (Types II and III). All of these taste cells are renewed throughout the life of an organism from a pool of uncommitted basal cells. Immature cells enter the bud at its base, maturing into one of the three mature cell types. How taste cells die and/or exit the bud, as well as the role of the glial-like cells in this process, remains unclear. Here we present morphological data obtained through Serial Blockface Scanning Electron Microscopy of murine circumvallate taste buds, revealing taste cells at the end of their life. Cells we identify as dying share morpholowgical features typical of apoptosis: swollen endoplasmic reticulum, large lysosomes, degrading organelles, distended outer nuclear membranes, heterochromatin reorganization, cell shrinkage, and cell and/or nuclear fragmentation. Most early stage dying cells have Type II cell morphologies, while a few display Type III cell features. Many dying cells maintain contacts with nerve fibers, but those postsynaptic fibers often appear to be detached from the main trunk of an afferent nerve. Dying cells, like mature Type II and III taste cells, are surrounded by glial-like Type I cells. In many instances Type I cells appear to be engulfing their dying neighbors, suggesting for them a novel, phagocytic role. Surprisingly, virtually no Type I cells display features of apoptosis, although they reportedly have the shortest residence time in taste buds. The ultimate fate of Type I cells therefore remains unknown. Table of Contents EntryO_ST_ABSMain PointsC_ST_ABSO_LIDying taste cells display morphologies consistent with apoptosis. C_LIO_LIGlial-like Type I cells engulf dying neighbors, perhaps acting as "undertakers." C_LIO_LIWe find no dying Type I cells--all early dying cells are taste transducing Type II or III cells. C_LI

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Structural comparisons of human and mouse fungiform taste buds

Taste buds are commonly studied in rodent models, but some differences exist between mice and humans in terms of gustatory mechanisms and sensitivities. Whether these functional differences are reflected in structural differences between species is unclear. Using immunofluorescent image stacks, we compared morphological and molecular characteristics of mouse and human fungiform taste buds. The results suggest that while the general features of fungiform taste buds are similar between mice and humans, several characteristics differ significantly. Human taste buds are larger and taller than those of mice, yet they contain similar numbers of taste cells. Taste buds in humans are more heavily innervated by gustatory nerve fibers expressing the purinergic receptor P2X3 showing a 40% higher innervation density than in mice. Like Type II cells of mice, a subset (about 30%) of cells in human taste buds is immunoreactive for PLC{beta}2. These PLC{beta}2-immunoreactive cells display CALHM1-immunoreactive puncta closely apposed to gustatory nerve fibers suggestive of channel-type synapses described in mice. These puncta, used as a measure of synaptic contact, are however significantly larger in humans compared to mice. Altogether these findings suggest that while many similarities exist in the structural organization of murine and human fungiform taste buds, significant differences do exist in taste bud size, innervation density, and size of synaptic contacts that may impact gustatory signal transmission.

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Taste Bud Connectome: Implications for Taste Information Processes

Taste buds contain 3 types of morphologically identifiable mature cells, 2 of which mediate transduction of specific taste qualities: Type III cells transduce sour while Type II cells transduce either sweet, bitter or umami. A long-standing controversy is whether the nerve fibers innervating these cells are wired specifically, in a labeled-line fashion, or non-specifically, leading to broad responsiveness across taste qualities, the so-called across-fiber system of encoding. Using serial blockface scanning electron microscopy through 5 circumvallate mouse taste buds, we reconstructed the patterns of connectivity of nerve fibers as well as the degree of potential interaction between the two types of taste transducing cells. Type II and Type III cells share few points of contact with one another, and display no morphologically identifiable synapses, suggesting limited direct interaction between these cell types. Of the 127 nerve fibers that make synaptic contacts with taste cells in the sampling volume, about 70% (n=91) synapse with only one taste cell. Of the remaining 36 fibers, 4 synapse with both Type II and Type III cells, the remainder synapsing exclusively with multiple Type II taste cells or multiple Type III cells. Since Type II and Type III cells transduce different taste qualities, the few mixed fibers do not follow a labeled-line organization according to taste quality information and show that connectional specificity in taste buds is not absolute. Significance StatementTaste buds, the sensory end organs for the sense of taste, contain multiple types of sensory cells, with each responding to one of the primary tastes: salt, sweet, sour, bitter and umami. A long-standing question is whether each type of taste cell is wired specifically to a unique set of nerve fibers conveying a "labeled-line" message to the brain. Using serial sections, we determined the neural connectivity in mouse circumvallate taste buds. The majority of individual nerve fibers connect to a single type of taste cell, but 3.1% of the fibers branch to receive input from taste cells known to have different specificities. Thus taste cannot entirely be carried along nerve fibers dedicated to single taste qualities.

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Genetic Deletion of TrpV1 and TrpA1 Does not Alter Avoidance of or Patterns of Brainstem Activation to Citric Acid in Mice

Exposure of the oral cavity to acidic solutions evokes not only a sensation of sour, but also of sharp or tangy. Acidic substances potentially stimulate both taste buds and acid-sensitive mucosal free nerve endings. Mice lacking taste function (P2X2/P2X3 double-KO mice) refuse acidic solutions similarly to wildtype mice and intraoral infusion of acidic solutions in these KO animals evokes substantial c-Fos activity within orosensory trigeminal nuclei as well as of the nucleus of the solitary tract (nTS) (Stratford et. al 2017). This residual acid-evoked, non-taste activity includes areas that receive inputs from trigeminal and glossopharyngeal peptidergic (CGRP-containing) nerve fibers that express TrpA1 and TrpV1 both of which are activated by low pH. We compared avoidance responses in wildtype (WT) and TrpA1/V1 double KO (TRPA1/V1Db1-/-) mice in brief-access behavioral assay (lickometer) to 1, 3, 10, 30 mM citric acid, along with 100 M SC45647 and H2O. Both WT and TRPA1/V1Db1-/- show similar avoidance, including to higher concentrations of citric acid (10 and 30 mM; pH 2.62 and pH 2.36 respectively), indicating that neither TrpA1 nor TrpV1 is necessary for the acid avoidance behavior in animals with an intact taste system. Similarly, induction of c-Fos in the nTS and dorsomedial spinal trigeminal nucleus was similar in the WT and TRPA1/V1Db1-/-animals. Taken together these results suggest non-TrpV1 and non-TrpA1 receptors underlie the residual responses to acids in mice lacking taste function.

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A Subset of Olfactory Sensory Neurons Express Forkhead Box J1-Driven eGFP

Forkhead box protein J1 (Foxj1), a member of the forkhead family transcription factors, is a transcriptional regulator of motile ciliogenesis. The nasal respiratory epithelium, but not olfactory epithelium, is lined with FOXJ1-expressing multiciliated epithelial cells with motile cilia. Using a Foxj1-eGFP reporter mouse, we find robust eGFP expression not only in the multi-ciliated cells of the respiratory epithelium, but in a distinctive small subset of olfactory sensory neurons in the olfactory epithelium. These eGFP-positive cells lie at the extreme apical part of the neuronal layer and are most numerous in dorsal-medial regions of olfactory epithelium. Interestingly, we observed a corresponding small number of glomeruli in the olfactory bulb wherein eGFP-labeled axons terminate, suggesting that the population of eGFP+ receptor cells expresses a limited number of olfactory receptors. Similarly, a subset of vomeronasal sensory neurons express eGFP but these distribute throughout the full height of the vomeronasal sensory epithelium. In keeping with this broad distribution of labeled vomeronasal receptor cells, eGFP labeled axons terminate in many glomeruli of the accessory olfactory bulb. These findings suggest that Foxj1-driven eGFP marks a specific population of olfactory and vomeronasal sensory neurons although neither receptor cell population possess motile cilia.

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Three-Dimensional Reconstructions of Mouse Circumvallate Taste Buds Using Serial Blockface Scanning Electron Microscopy: I. Cell Types and the Apical Region of the Taste Bud

Taste buds comprise four types of taste cells: 3 mature, elongate types: Type I, Type II, Type III; and basally-situated, immature post-mitotic Type IV cells. We employed serial blockface scanning electron microscopy to delineate the characteristics and interrelationships of the taste cells in the circumvallate papillae of adult mice. Type I cells have an indented, elongate nucleus with invaginations, folded plasma membrane, and multiple apical microvilli in the taste pore. Type I microvilli may be either restricted to the bottom of the pore or extend outward reaching midway up into the taste pore. Type II cells (aka receptor cells) are characterized by a large round or oval nucleus, a single apical microvillus extending through the taste pore, and specialized \"atypical\" mitochondria at functional points of contact with nerve fibers. Type III cells (aka \"synaptic cells\") are elongate with an indented nucleus, possess a single, apical microvillus extending through the taste pore and are characterized by a small accumulation of synaptic vesicles at points of contact with nerve fibers. About one-quarter of Type III cells also exhibit an atypical mitochondrion amidst the presynaptic vesicle clusters at the synapse. Type IV cells (non-proliferative \"basal cells\") have a nucleus in the lower quarter of the taste bud but have a foot process extending to the basement membrane often contacting nerve processes along the way. Type I cells represent just over 50% of the population, whereas Type II, Type III, and Type IV (basal cells) represent 19%, 15%, and 14% respectively.

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