Cyclophosphamide induces the loss of taste bud innervation in mice
1
Citation
34
Reference
10
Related Paper
Citation Trend
Abstract:
Abstract Many common chemotherapeutics produce disruptions in the sense of taste which can lead to loss of appetite, nutritional imbalance, and reduced quality of life, especially if taste loss persists after treatment ends. Cyclophosphamide (CYP), an alkylating chemotherapeutic agent, affects taste sensitivity through its cytotoxic effects on mature taster receptor cells (TRCs) and on taste progenitor cell populations, retarding the capacity to replace TRCs. Mechanistic studies have focused primarily on taste cells, however, taste signaling requires communication between TRCs and the gustatory nerve fibers which innervate them. Here, we evaluate the effect of CYP on the peripheral gustatory nerve fibers that innervate the taste bud. Following histological analysis of tongue tissues, we find that CYP reduces innervation within the fungiform and circumvallate taste buds within 4-8 days after administration. To better understand the dynamics of the denervation process, we used 2-photon intravital imaging to observe the peripheral gustatory neuron arbors within individual fungiform taste buds before and after CYP treatment. We find that gustatory fibers retract from the taste bud proper but are maintained within the central papilla core. These data indicate that, in addition to TRCs, gustatory nerve fibers are also affected by CYP treatment. Because the connectivity between TRCs and gustatory neurons must be re-established for proper function, gustatory fibers should continue to be included in future studies to understand the mechanisms leading to chemotherapy-induced persistent taste loss.Keywords:
Taste bud
Lingual papilla
Taste receptor
Lingual papilla
Taste receptor
Taste bud
Cite
Citations (50)
Abstract Many common chemotherapeutics produce disruptions in the sense of taste which can lead to loss of appetite, nutritional imbalance, and reduced quality of life, especially if taste loss persists after treatment ends. Cyclophosphamide (CYP), an alkylating chemotherapeutic agent, affects taste sensitivity through its cytotoxic effects on mature taste receptor cells (TRCs) and on taste progenitor cell populations, retarding the capacity to replace TRCs. Mechanistic studies have focused primarily on taste cells, however, taste signaling requires communication between TRCs and the gustatory nerve fibers that innervate them. Here, we evaluate cyclophosphamide’s effects on the peripheral gustatory nerve fibers that innervate the taste buds. Following histological analysis of tongue tissues, we find that CYP reduces innervation within the fungiform and circumvallates taste buds within 4 days after administration. To better understand the dynamics of the denervation process, we used 2-photon intravital imaging to visualize the peripheral gustatory nerve fibers within individual fungiform taste buds up to 20 days after CYP treatment. We find that gustatory fibers retract from the taste bud properly but are maintained within the central papilla core. These data indicate that in addition to TRCs, gustatory nerve fibers are also affected by CYP treatment. Because the connectivity between TRCs and gustatory neurons must be re-established for proper function, gustatory fibers should continue to be included in future studies to understand the mechanisms leading to chemotherapy-induced persistent taste loss.
Taste bud
Cite
Citations (2)
The experiment, employing histochemical methods, was undertaken to discern the distribution of phosphatases in the taste buds of the fungiform papillae, foliate papillae and vallate papillae of normal rat's tongue. The phosphatase activity was compared with that in rats after exposuing the tongue to gymnemic acid, a taste modifier which suppresses sweetness and to that in rats with degenerating taste buds following bilateral transection of the chorda tympani and glossopharyngeal nerve. 1. Distribution of phosphatases in the normal papillae A. Alkaline phosphatase activity was not present on the superficial epithelium of fungiform papillae except on the top of some fungiform papillae. Intense alkaline phosphatase activity was present in the superficial layers of the taste bud-bearing epithelium of the foliate and vallate papillae. Taste bud cells had, in general, no activity but occasional cells did have a slight reaction. B. Acid phosphatase activity was present in the taste buds of all papillae. Intense reaction was localized in the supranuclear cytoplasm of the taste bud cells with a variation in each taste bud cell. C. Adenosine triphosphatase activity was present in the taste buds of all papillae. Intense activity was found on the cell membrane and at the taste pores. 2. Distribution of phosphatases in the papillae affected by gymnemic acid A. All papillae showed the same alkaline phosphatase activity at that in the normal papillae. B. All papillae showed the same acid phosphatase activity as that in the normal papillae. C. The foliate and vallate papillae showed the same adenosine triphoshatase activity, but it was found that the activity decreased on the taste cell membrane of the fungiform papillae and showed no clear boundary of the taste bud cells. This suggested that gymnemic acid might have an effect on adenosine triphosphatase activity, therefore, this might be one of the causes for suppression of sweet sensitivity by gymnemic acid. 3. Distribution of phosphatases in the papillae following bilateral chorda tympani and glossopharyngeal nerve transection The taste buds in foliate and vallate papillae were reduced in width four days after denervation and in length five days after denervation. In addition, the taste pores disappeared and the basal cells proliferated at the basal areas of the degenerated taste buds, following replacement by squamous epithelium. A. Alkaline phosphatase activity was not positive on the superficial epithelium of fungiform papillae on the fifth postoperative day. There was virtually an increase of reaction zone in width for the alkaline phosphatase activity of the superficial layers of the stratified squamous epithelium containing the taste buds of foliate and vallate papillae from three days to four days after denervation and there was a slow decrease in width for alkaline phosphatase activity. Alkaline phosphatase activity persisted even on the ninth day after denervation. B. Acid phosphatase activity increased in intensity following the progressive degeneration of the taste buds. Intense activity was found even in the infranuclear cytoplasm of the taste bud cells indicating the same intensity in the cells. C. Adenosine triphosphatase activity decreased in intensity on the cell membrane of the taste buds three days after denervation and showed the same activity in the taste buds. Thereafter, the activity decreased in intensity. This suggested that adenosine triphosphatase was most affected by denervation. The results of the present experiment showed that adenosine triphosphatase did play a significant role in the perception of taste-stimulus and maintenance of the taste buds. This might partially prove that the enzymes are related to the mechanism of taste.
Lingual papilla
Taste bud
Taste receptor
Cite
Citations (0)
Lingual papilla
Taste bud
Major duodenal papilla
Taste receptor
Cite
Citations (14)
The distribution of taste buds on the fungiform and circumvallate papillae of the cow tongue has been determined. The two tongues studied were from Holstein-Friesian cows four to six years of age; they contained 14,765 and 21,691 taste buds, respectively. The tip of the tongue is well supplied with fungiform papillae, and the posterior portion contains the circumvallate papillae. The midportion of the tongue contains relatively few taste papillae. The fungiform papillae contained 1,580 and 1,838 taste buds on the two tongues, respectively, and the circumvallate papillae were estimated to contain 13,185 and 19,853 taste buds. The highest concentration of taste buds therefore occurs in the circumvallate papillae; these relatively few papillae contain approximately 90% of the taste buds. On a circumvallate papilla, taste buds are found only on the papillary sidewall, with none either on the apical surface of the papilla or on the outer wall of the moat.
Lingual papilla
Major duodenal papilla
Taste receptor
Taste bud
Cite
Citations (44)
Abstract The sensitivity of taste in mammals varies due to quantitative and qualitative differences in the structure of the taste perception organs. Gustatory perception is made possible by the peripheral chemosensory organs, i.e., the taste buds, which are distributed in the epithelium of the taste papillae of the palate, tongue, epiglottis, throat and larynx. Each taste bud consists of a community of ~100 cells that process and integrate taste information with metabolic needs. Mammalian taste buds are contained in circumvallate, fungiform and foliate papillae and react to sweet, salty, sour, bitter and umami stimuli. The sensitivity of the taste buds for individual taste stimuli varies extensively and depends on the type of papillae and the part of the oral cavity in which they are located. There are at least three different cell types found in mammalian taste buds: type I cells, receptor (type II) cells and presynaptic (type III) cells. This review focuses on the biophysiological mechanisms of action of the various taste stimuli in humans. Currently, the best-characterized proteins are the receptors (GPCR). In addition, the activation of bitter, sweet and umami tastes are relatively well known, but the activation of salty and sour tastes has yet to be clearly explained.
Umami
Taste bud
Taste receptor
Lingual papilla
Aftertaste
Epiglottis
GPR120
Cite
Citations (42)
Abstract O akley , B. Reformation of taste buds by crossed sensory nervps in the rat's tongue . Acta physiol. scand. 1970. 79 . 88–94. Rat taste buds degenerate and disappear when their nerve supply is cut. Regeneration of the taste nerve fibres causes certain epithelial cells to differentiate into slender receptor cells comprising the taste bud. In this study by cross‐union the glossopharyngeal (IXth) nerve was made to innervate the front of the tongue, and in other rats the chorda tympani nerve was forced to grow to the back of the tongue. These cross‐regenerated sensory nerves were able to cause differentiation of epithelial cells into taste buds, whose number and distribution were histologically determined 15 weeks postoperatively. The cross‐innervating IXth nerve reestablished taste buds in the existing fungiform papillae in conformity with the normal number and distribution of taste buds at the front of the tongue. The chorda tympani, forced to innervate the hack of the tongue, reestablish in the foliae papillae more than 1.5 times as many taste buds as it normally innervates. The number of taste buds normally innervated by the chorda tympani must, therefore, be restricted by the capacity of the anterior tongue tissue to respond to this nerve's influence. This study indicates that the distribution and total number of taste buds in the rat tongue is limited by the inherent nature of the tongue region being innervated (tissue‐specific) rather than by the type of nerve supplying the taste buds (nerve‐specific).
Lingual papilla
Taste bud
Taste receptor
Glossopharyngeal nerve
Chorda
Lingual nerve
Cite
Citations (54)
Abstract Some hypotheses on taste reception have implicated lipids of taste cells as major receptor constitutents. This study reports detailed lipid profiles of the taste bud‐containing epidermis from circumvallate papillae and fungiform papillae as well as profiles from two non‐taste bud tissues: circumvallate papillae dermis and epidermis from the lateral posterior of the tongue. Differences in levels of triglycerides and phosphatidylcholines were observed but these were not directly related to the presence of taste buds. At this level of analysis, it is evident that there are no unusual distributions of phospholipid classes in the taste bud epidermis when compared with the non‐taste bud lingual epidermis.
Taste bud
Lingual papilla
Epidermis (zoology)
Taste receptor
Cite
Citations (9)
Taste buds on the mammalian tongue are confined to the epithelium of three types of gustatory papillae: the fungiform(FF), circumvallate(CV), and foliate(FL) . Because taste bud cells are periodically renewed, the morphogenesis, number and function of taste buds are changing with the age. Gustatory papillae are unique in the tongue in their ability to support the formation and to maintain taste buds. Evidence showed that the taste papillae play a major role in determining the number, location and size of taste buds, as well as their maintenance. Although several factors (signaling molecules, gustatory nerve fibers, etc. ) have many affinities with the development of the papillae and taste buds, the specific mechanism that regulate initiation, growth, and maintenance of the papillae and taste buds are still not clear yet.
Lingual papilla
Taste receptor
Taste bud
Cite
Citations (0)
Abstract Many common chemotherapeutics produce disruptions in the sense of taste which can lead to loss of appetite, nutritional imbalance, and reduced quality of life, especially if taste loss persists after treatment ends. Cyclophosphamide (CYP), an alkylating chemotherapeutic agent, affects taste sensitivity through its cytotoxic effects on mature taster receptor cells (TRCs) and on taste progenitor cell populations, retarding the capacity to replace TRCs. Mechanistic studies have focused primarily on taste cells, however, taste signaling requires communication between TRCs and the gustatory nerve fibers which innervate them. Here, we evaluate the effect of CYP on the peripheral gustatory nerve fibers that innervate the taste bud. Following histological analysis of tongue tissues, we find that CYP reduces innervation within the fungiform and circumvallate taste buds within 4-8 days after administration. To better understand the dynamics of the denervation process, we used 2-photon intravital imaging to observe the peripheral gustatory neuron arbors within individual fungiform taste buds before and after CYP treatment. We find that gustatory fibers retract from the taste bud proper but are maintained within the central papilla core. These data indicate that, in addition to TRCs, gustatory nerve fibers are also affected by CYP treatment. Because the connectivity between TRCs and gustatory neurons must be re-established for proper function, gustatory fibers should continue to be included in future studies to understand the mechanisms leading to chemotherapy-induced persistent taste loss.
Taste bud
Lingual papilla
Taste receptor
Cite
Citations (1)