Biology of Taste Buds and the Clinical Problem of Taste Loss
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70 THE ANATOMICAL RECORD (NEW ANAT.)
FEATURE ARTICLE
Biology of Taste Buds and the Clinical Problem
of Taste Loss
GINA M. NELSON
Taste buds are the anatomical structures that mediate the sense of taste. They comprise taste cells and nerve fibers
within specialized epithelial structures. Taste cells are traditionally described by histologic methods as basal, dark,
intermediate, and light cells, with the nerve fibers surrounding and infiltrating the taste buds. By means of
immunohistochemical methods, taste cells and gustatory nerve fibers can be classified in functional groups based on
the expression of various cell adhesion molecules and other proteins. When taste buds become damaged, the loss of
the ability to taste results. This loss is not uncommon and can impact health and quality of life. Patients who receive
radiation therapy for head and neck cancer often experience taste loss, which leads to compromised nutritional intake
and a worse outcome than patients who do not experience taste loss. The mode of radiation damage to taste cells and
nerve fibers has been investigated using cell adhesion molecules, synaptic vesicle proteins, and other cell markers.
The light and intermediate cells are preferentially affected by ionizing radiation, whereas the nerve fibers remain
structurally intact. Experimental studies of radiation-induced taste loss are performed via a unique animal/human
model. Anat. Rec. (New Anat.) 253:70–78, 1998. r 1998 Wiley-Liss, Inc.
KEY WORDS: taste buds; taste loss; head/neck cancer; radiation therapy; radiation model; cancer therapy
WHAT MAKES UP THE SENSE plants, as they have a very bitter taste which come in four varieties. Filliform
OF TASTE? due to the presence of various alkaloid papillae are the most numerous and
compounds. appear as short, rough structures cov-
Of the five senses, taste is the sense What happens when our sense of ered with thick keratinized epithelium
which is least thought about by most taste goes awry? The understanding of (they feel particularly rough on a cat’s
people. Unlike the senses of vision and the mechanisms of vision and hearing tongue). They do not contain taste
hearing, taste does not have much is far ahead of the understanding of buds. The fungiform papillae are dis-
impact on our day-to-day life—or does the mechanisms of taste. Glasses and persed across the surface of the tongue.
it? Taste buds play a greater role in our artificial lenses are available to correct They are more box-like, with a connec-
lives than we might imagine. In combi- vision deficits, and hearing aids are tive tissue core and a thin covering of
nation with our sense of smell, we are available for those with diminished epithelium. Most of the fungiform pa-
able to enjoy the aroma and taste of hearing, but what corrective aids are pillae contain a single taste bud on the
our food and drink. More importantly, available for the loss of taste? Have tip. The larger circumvallate papillae
we recognize spoiled food, if not by you ever known a person, a relative or are located on the posterior aspect of
the smell then by the terrible taste. For a friend perhaps, who cannot taste? the dorsal surface, appearing as pin-
our ancestors more than for modern What is the world of taste like for that
cushions with a surrounding trough,
humans, taste warned of poisonous person? What causes taste loss? Is the
called a crypt. The crypt is lined by an
ability to taste affected by illness or by
epithelium, called the gustatory epithe-
therapies designed to treat these ill-
lium, which contains several taste buds.
nesses?
Dr. Nelson has long had an interest in The pores of the taste buds open into
chemoreceptive sciences, beginning
with invertebrate chemoreception. She
the crypt. In humans there are 12–15
has an MD and PhD from the University WHERE ARE MY TASTE BUDS? circumvallate papillae, but in rodents
of Colorado Health Sciences Center, (as in mice or rats) there is only one.
where she developed an animal model Taste buds are the anatomical struc-
of radiation-induced taste loss. Dr. Nel- tures which contain the receptor cells Foliate papillae lie on the lateral sides
son is currently a resident in anatomic that mediate the sense of taste. Taste of the tongue and appear like slits.
pathology at the University of Iowa Hos-
pitals and Clinics and plans to continue buds are found in the oral cavity, pri- These are less developed in rats and
work on the animal model and human marily on the tongue but also on the humans than they are in other species.
studies in taste loss through the Depart- Each taste bud is oval (Fig. 2) and
ment of Anatomy and Cell Biology after
palate, back of the mouth, pharynx,
residency. epiglottis, and larynx. The tongue (Fig. opens to the epithelial surface via a
1) is covered with numerous papillae small opening called a taste pore. From
r 1998 Wiley-Liss, Inc.REVIEW THE ANATOMICAL RECORD (NEW ANAT.) 71
bud, and perigemmal fibers are those
around the taste bud. The intragem-
mal nerve fibers are the nerve fibers
which receive synaptic contacts from
all three types of taste cells.4 While the
perigemmal fibers are generally
thought to be outside of the taste bud,
some perigemmal nerve fibers enter
the taste bud from the side. Some
perigemmal nerve fibers reach the sur-
face of the epithelium; others reach
around the taste pore. In addition,
both Type II and III cells form two
types of synaptic contacts with the
intragemmal nerve fibers, thought to
represent efferent (efferent 5 nerve
fibers carrying information from the
brain) and afferent synaptic contacts.5
It has been proposed that the sub-
Fig. 1. Dorsal surface of tongue. Pictured is the upper surface of the tongue showing the stance P–containing fibers within the
location of the pincushion–shaped circumvallate papillae on the very back of the tongue and taste bud may mediate oral pain.6
the fungiform papillae over the surface between the circumvallate papillae and the tip of the A nutritional, or trophic, interaction
tongue.
(i.e., one cell emits a substance that a
second cell needs to grow) between
this pore protrudes the microvilli aris- and dark cells. Which taste cell type is the nerve fiber and taste buds exists.
ing from the tips of the individual actually the receptor has not been Interruption of the nerve fiber by ei-
taste cells. Each taste bud contains proven, although every type has been ther cut or crush injury results in the
50–100 taste receptor cells and sup- proposed. Taste cells have also been
port cells. Taste cells are described as designated as Type I, II, III, and IV, Taste buds play a greater
basal, dark, intermediate, and light, with Type I being similar to dark cells,
based on electron microscopic charac- Type II similar to light cells, and Type role in our lives than we
teristics1 (Fig. 2). The basal cells are at IV being the basal cells. In this schema, might imagine.
the base of the taste bud and consti- the Type III cells are like intermediate
tute a proliferative population of cells. cells and are thought to be the gusta-
They divide to produce postmitotic tory receptor cells,2 primarily due to
light, intermediate, and dark taste cells the presence of what are believed to be disappearance of the taste buds (Fig.
with a life span of 10–11 days. Dark afferent synaptic contacts* (afferent 5 3). If the nerve fiber is allowed to grow
cells are defined by a dark cytoplasm nerve fibers carrying information to back, the taste buds will reappear. This
(electron-dense), dense-core granules the brain). The dense-core vesicles are indicates that there is an unknown
(small vesicles with a dark center) at located in dark cells and to a lesser molecule originating from the nerve
the tip of the cell, indentations in the extent in intermediate cells1 in associa- fiber that is required for the taste buds
nuclear membrane, and collections of tion with both the tip of the cells and to retain their form. The mechanisms
heterochromatin (the DNA) along the the presynaptic regions. These vesicles of sensory transduction of various taste
inner edge of the nucleus. Light cells are thought to contain serotonin.3 stimuli across the taste cell membrane
are characterized by a light cytoplasm Fungiform taste buds are inner- is a topic worthy of its own review, and
(electron-lucent), clear vesicles and mi- vated by the chorda tympani branch of the reader is referred to excellent pa-
tochondria in the tip of the cell, and a cranial nerve VII, while the circumval- pers on this topic.7
round to oval nucleus with less hetero- late taste buds are innervated by cra-
chromatin (DNA) along the inner edge. nial nerve IX. Taste buds in the phar-
ANATOMICAL CONCEPTS BASED
Intermediate cells have characteristics ynx are innervated by cranial nerve X.
that are intermediate between the light In the region of the taste buds, nerve ON CELL MARKERS
fibers are described by anatomical lo- Until recently, the elements of the taste
*Authors vary in their use of the differ- cation (refer to Fig. 2). The subepithe- system have been described anatomi-
ent systems of nomenclature. While lial plexus are the nerve fibers in the cally and histologically. An alternative
some correlations have been made connective tissue beneath the gusta- method is to describe the components
between the two systems, they are not tory epithelium (the epithelium con- of the taste system based on their
totally equivalent. The information taining the taste buds). The basal function, which makes sense biologi-
here is given in relation to the article plexus nerve fibers are in the basal cally. By comparison, vision receptors
in which it was originally presented, portion of each bud, forming a kind of are the rods and cones, and the vestibu-
maintaining the system by which it a nest around the basal cells. Intragem- lar and cochlear nerves transmit spe-
was described. mal fibers are those within the taste cific sensory information in the ear.72 THE ANATOMICAL RECORD (NEW ANAT.) REVIEW Fig. 2. Schematic of a normal taste bud. All of the elements of a taste bud are illustrated. The taste bud contains basal cells (B) in the lower portion of the bud and all three types of taste cells extending upward to the opening at the top, the taste pore. The light cells (L), intermediate cells (I), and dark cells (D) are pictured with some of the features that characterize each cell type. In addition, the intragemmal and perigemmal nerve fibers are seen. The nerve fibers are present in the subepithelial connective tissue and enter each bud from the base. The red fibers represent the nerve fibers which contain synaptic vesicle proteins, and the black fibers represent nerve fibers which contain peptides. S, synapse. Fig. 3. Damage to the taste bud following nerve injury. After crushing or cutting the nerve (e.g., glossopharyngeal) that innervates the taste buds, the taste buds degenerate. Small, atrophic buds remain, as seen in the illustration. If the nerve fiber regenerates, the taste buds will grow back.
REVIEW THE ANATOMICAL RECORD (NEW ANAT.) 73
nerve fibers classified in this manner
can be studied in various experimental
situations. Often the expression of a
particular protein is found primarily
in a histologically designated type of
taste cell (i.e., light cells), although
only a few of the light cells contain the
protein. Sometimes a few cells from
two groups will express a particular
protein (i.e., a few of the light and
intermediate cells). This suggests that
the histological classifications of light,
intermediate, and dark do not corre-
late with function.
Examples of various proteins ex-
pressed by taste cells include the blood
group antigens,8 the transmembrane
G protein gusducin9 neural cell adhe-
sion molecule (NCAM),10 the calcium
binding protein calbindin,11 and kerat-
ins.12 Some are located in specific taste
cell types; others are not. Many other
examples are described in the litera-
ture.
Using light and electron micro-
scopic immunohistochemistry, we
Fig. 4. The technique of immunohistochemistry. The protein of interest (pentagon in the
illustration), termed the antigen, is isolated and purified and then injected into the host mouse. demonstrated the presence of NCAM10
The mouse’s immune system sees the antigen as a foreign molecule and makes antibodies and a form of growth associated pro-
against it. The antibodies are then taken from the mouse’s serum. A thin piece of tissue from a tein (GAP) in taste cells recognized by
second animal is put on a glass slide, and the antibody is applied to it. The antibody will the antibody designated B5013 (Fig. 5).
recognize the antigen in the tissue (the pentagon) and stick to it. In order to visualize where the NCAM appears as smooth, continuous
antibody is located, a secondary antibody is applied which recognizes the first. The secondary
antibody has a tag on the end (star) which can be seen in a microscope equipped for
outlines on long, thin, distinct taste
fluorescence microscopy. cells identified as light or intermediate
cells. The B50 antibody produces a
diffuse label throughout taste cells
identified as intermediate or dark cells,
These descriptors are related to the from the animal being investigated
located in the mid to apical portion of
function of the anatomical structure. (usually not a mouse) are put on slides,
the taste bud. These cells appear differ-
It would be logical to take the same and the anti-X antibodies are added.
ent from the thin, elongated cells la-
approach for the sense of taste and The antibodies attach to the X mol-
beled by the NCAM antibody. Not all
designate a salt receptor or a bitter- ecules in the tissue. Then a secondary
of the intermediate and dark cells la-
taste fiber. However, the details are not antibody with a fluorescent tag is at-
bel. Experiments with NCAM and B50
known at a sufficient level to always tached to the first antibody. A micro-
together indicate that these proteins
determine the functional designations. scope equipped to view the fluorescent
occur on separate populations of taste
Investigators in many laboratories are tag is then used to visualize where the
cells. No cell in normal taste buds ever
improving on the knowledge of the anti-X antibodies attached. The corre-
showed reactivity to both of these anti-
taste system, so this descriptive sys- lation can be made that protein X
bodies together.
tem may be realized in the future. resides in the location where fluores-
One way to approach this is to iden- cent patterns are seen.
tify groups of taste cells or nerve fibers The markers used to identify cells
ANATOMICAL CONCEPTS BASED
based on the expression of a particular and nerve fibers can be cell surface
protein. With a technique called immu- molecules, neurotransmitters, struc- ON NERVE FIBER MARKERS
nohistochemistry, an antibody is made tural proteins, synaptic vesicle pro- Nerve fibers can also be described in a
which recognizes a particular pro- teins, peptides, blood group markers, similar fashion. In the construct of a
tein—for example, protein X (Fig. 4). enzymes, lectins, or many other types sensory system, there are nerve fibers
Simply, an amount of protein X is of proteins. The identification of a to bring the signal of the perceived
injected into a mouse, the host animal. group of taste cells or nerve fibers that stimulus to the brain (the nerve fibers
The immune system of the host gener- share a given histochemical property which are postsynaptic to the taste
ates antibodies directed against pro- suggests that these cells or nerve fibers cells, the afferent fibers) and nerve
tein X. The serum is removed from the have a common biological characteris- fibers to bring modulating informa-
animal, and the new anti-X antibodies tic which may be more closely related tion to the sensory cells (efferent fi-
are purified. Thin sections of tissue to a common function. Taste cells or bers). There may also be nerve fibers74 THE ANATOMICAL RECORD (NEW ANAT.) REVIEW Fig. 5. Taste bud with antibody-labeled taste cells. After application of an antibody which recognizes NCAM, some of the light to intermediate taste cells appear bright, having a long, thin outline (taste cells with white dots in illustration). The application of the B50 antibody labels some of the dark cells with a more diffuse pattern (bright taste cell without dot). In this example, the nerve fibers are not labeled. Fig. 6. The effects of radiation on taste buds. At the peak of radiation damage (approximately 7 days), some of the light to intermediate taste cells are degenerating, but the dark cells and all subtypes of nerve fibers remain intact. The nerve fibers containing synaptic vesicle proteins (red) and the nerve fibers containing peptides (black) remain as they were in the normal taste bud. The overall pattern of degeneration is different than that seen in the taste buds affected by nerve cut (refer to Fig. 3).
REVIEW THE ANATOMICAL RECORD (NEW ANAT.) 75
to carry visceral information (hot, cold, group of fibers that contain SV2 only rule out that the taste loss is caused by
pain, etc.) which may or may not be and CGRP only. All synaptophysin the underlying disease process. Most
located within the taste bud. In an nerve fibers are also PGP 9.5 nerve of the drugs associated with taste loss
effort to identify these various types of fibers, but the reverse is not true. Even affect the turnover of cells, as is seen
nerve fibers, much like the taste cells, though there is some overlap in the in other systems, but other mecha-
immunohistochemical techniques described categories of gustatory nerve nisms are possible. Drugs usually in-
were utilized to demonstrate that dif- fibers, the results of examining the duce a temporary effect which dimin-
ferent nerve fibers express different distribution of these proteins in the ishes after the drug is discontinued.
proteins. For example, many perigem- gustatory nerve fibers allows their divi- Chemotherapy employs drugs associ-
mal fibers contain the peptide sub- sion into functional groups: postsynap- ated with taste loss. A few examples
stance P, while others contain calcito- tic intragemmal (labeled with synaptic include methotrexate and dexametha-
nin gene-related peptide (CGRP). The vesicle proteins), nonpostsynaptic in- sone, antihypertensives, antimicrobial
intragemmal nerve fibers contain syn- tragemmal (labeled with peptides), agents, and antiproliferative agents.18
aptic vesicle proteins, like synaptophy- perigemmal (labeled with peptides),
sin.14 (Of note, even though all of the and nerve fibers around the taste pore
types of taste cells, light, intermediate, (labeled with SV2). This gives us a tool RADIATION THERAPY–INDUCED
and dark, make synaptic contacts with to follow what happens to these catego- TASTE LOSS
the intragemmal nerve fibers,4 none of ries of nerve fibers during experimen-
Radiation is often used either alone or
the synaptic vesicle proteins to date tal manipulation, as described below.
in addition to surgery to treat various
have been found to label the presynap- types of cancers. The typical dose for
tic vesicles located within the taste patients with head and neck cancer or
cells). TASTE LOSS IN HUMANS oral cancer is 5,000–7,000 cGy. (A cen-
Numerous basal plexus nerve fibers While not discussed widely in the bio- tiGrey (cGy) is the deposition of 1 erg
and nerve fibers in the dermis or in the chemical literature, ageusia (taste loss) of energy per 100 g of tissue.) It is
core of the fungiform papillae also and hypogeusia (decrease in taste) and administered in divided doses of about
contain the synaptic vesicle proteins dysgeusia (abnormal taste) are wide- 180 cGy/week until the desired dose is
and peptides. Electron micrographs spread and associated with a variety of achieved. Radiation is composed of
show that small vesicles within these illnesses, from common to obscure. charged particles that disrupt the elec-
nerve processes, measuring 40–60 nm Taste loss occurs as a natural phenom- tron orbital structure of the atoms in
in diameter, are the same size as the enon of aging and also in response to the tissue, causing tissue destruc-
vesicles described as containing the normal changes such as pregnancy tion.19 The theory behind the therapy
synaptic vesicle proteins in other loca- and menopause.17 Poor dentition and is to disrupt the proliferative capacity
tions. The nerve fibers that label with hygiene are common oral conditions of the tumor, thus destroying it, while
synaptic vesicle proteins are postsyn- that affect taste. Patients with xerosto- doing as little damage as possible to
aptic to some taste cells.14 All of the mia (dry mouth), Sjögren syndrome the normal tissue. Since the tissue
nerve fibers, both intragemmal and (inflammation of the salivary glands lining the mouth and the gastrointesti-
perigemmal, can be identified with resulting in a dry mouth), and zinc nal tract divides at a faster rate than
proteins common to most neurons, deficiency may also experience taste tissues of other organs (e.g., liver),
like protein gene product 9.5 (PGP loss. Other conditions in which taste they are more susceptible to radiation
9.5) and S100.15 loss may occur include liver and kid- damage. The resulting side effects to
When the synaptic vesicle protein- ney disorders, diabetes mellitus, de- the oral cavity include mucositis (swell-
containing nerve fibers are compared pression, and surgical procedures ing and tenderness of the oral mucosa
with those containing peptides or PGP around the chorda tympani or glosso- with sloughing off of dead cells), xero-
9.5 using double labeled fluorescence pharyngeal nerve. Patients with head stomia, and taste loss.
immunohistochemistry, the two types trauma and epilepsy may also experi- Of particular interest is the taste
of nerve fibers are not distinct groups, ence taste loss. Taste loss can range loss that occurs with the administra-
and the location of the proteins does from mild to severe, resulting in subse- tion of radiation therapy, termed post-
not correlate exactly with the anatomi- quent decrease in nutritional intake. irradiation gustatory dysfunction. It
cal classifications. The nerve fibers (Many investigators contributed to the occurs following administration of ra-
containing synaptophysin have a small accumulation of this knowledge. The diation to the region of the oral cavity
subset that also contain CGRP. There reader is referred to the many chap- and thus the taste buds. In some pa-
are occasional intragemmal nerve fi- ters that cover these topics in more tients, the taste loss can be severe. The
bers that contain CGRP only. Most detail in Getchell et al.18) loss of taste has been reported in the
perigemmal nerve fibers show labeling Various types of therapy can also literature only as case reports and as
with either synaptophysin or CGRP. induce taste loss. Numerous drugs are occasional small studies. The loss of
Analysis of SV2 (another synaptic associated with taste loss. However, an taste due to radiation therapy is a
vesicle protein16) and CGRP gives incomplete understanding of how the common problem which is underrep-
slightly different results. For both the taste system works and the interaction resented in the literature. In patients
intragemmal and perigemmal nerve of drug compounds with the taste who lose their sense of taste, one re-
fibers, there is a group of fibers that system make it difficult to assign the sult is a marked decrease in the ability
contain both proteins, and there is a taste loss to a drug alone. One cannot to eat and thus a decrease in nutrition76 THE ANATOMICAL RECORD (NEW ANAT.) REVIEW
intake. These patients experience two possible sites of radiation damage possibly associated to depleted zinc
greater weight loss than those patients leading to taste loss: (1) the intragem- stores.20
who do not report a change in taste,20 mal nerve fibers and (2) the taste cells. In an attempt to test these various
and it has been well documented that If the nerve fibers are the site of dam- hypotheses, the projects described
these patients have a worse outcome age, one possibility could be a signifi- herein use a novel approach of combin-
than the patients who do not lose their cant physical loss in the population of ing histological evaluation with behav-
sense of taste and are able to maintain postsynaptic intragemmal nerve fi- ioral assessment in an effective model
their food intake and nutritional sup- bers. Since the neurons are a nondivid- of radiation-induced taste loss in rats,
port.21 Nutritional supplements have ing population of cells, they are as well as extending the studies to
been shown to positively impact can- thought to be generally radioresistant. human cancer patients receiving radia-
cer therapy when administered in ad- However, disruption of the functional tion therapy. In this model, hypoth-
dition to the therapy for the disease.22 integrity of the neuron could lead to eses about the function of taste cells
The changes in the taste thresholds the symptom of taste loss. Synaptic and nerve fibers can be formulated
for all tastes (sweet, sour, bitter, salty) uncoupling or disruption of mem- based on quantitative behavioral data.
varies among treated patients. Qui- brane integrity leading to a disruption The tool we have designed to direct
nine taste (bitter) is most consistently in the contact between the taste cells the radiation to the surface of the
lost, but the loss of sugar and salt taste and nerve fibers, resulting in the inabil- tongue results in a method of radia-
varies considerably among patients. ity to conduct action potentials, is a tion which eliminates the problematic
Decreases in taste thresholds begin possibility. A similar finding was dem- side effects encountered with conven-
from treatment with as little as 200– onstrated in the disruption of neuro- tional radiation, typically mucositis
400 cGy.23 Also, a discrepancy is noted muscular junctions in mouse tongues and xerostomia. In addition, the labels
between the speed with which taste following a single dose of radiation.28 for the various subpopulations of taste
sensation is lost and the deterioration Other investigators have actually pro- cells and nerve fibers make it possible
of the taste cells. The taste buds degen- posed the nerve fiber as the site of to follow what happens to each of
erate 6–7 days after irradiation, but damage leading to taste loss but mostly these components of the taste system
taste alteration is seen as early as 2–3 incidentally.24,25 following radiation. The eventual goal
days after irradiation. In mice, follow- of this model is to understand the
ing a single radiation dose between biological mechanisms underlying ra-
1,000 and 4,000 cGy, taste buds are diation-induced taste loss so that meth-
Radiation affects ods to prevent taste loss can be devel-
either entirely destroyed or, if they
remain, lose 30–50% of their cells. The elements of cells that oped and thus improve the quality of
life and treatment outcome of these
taste bud degeneration peaks at 9 days cannot easily be cancer patients.
after injury, and then the taste buds
begin to regenerate.24 In another
repaired or replaced,
study,25 single doses of 850 cGy cause namely the DNA. RADIATION-INDUCED TASTE LOSS
a smaller number of taste buds to
degenerate, and recovery begins IN ANIMALS
sooner. At a single dose of 2,200 cGy, In studies described previously,29 the
the taste buds degenerate much faster. The second possible site of damage effects of radiation on the taste system
This illustrates that the number of is the taste cells. Previously it has been were examined in rats given a single
taste buds that degenerate is related to demonstrated that following irradia- dose (1,700 cGy) of radiation to the
the size of the dose. When permanent tion the cells within the taste bud lose oral cavity. Behavioral measurements
damage occurs, it is usually with accu- their characteristic histological appear- were made based on the consumption
mulated doses exceeding 6,000 cGy. ances (light, intermediate, and dark) of either a 1.8% NaCl (salt) solution
Long-term effects include lowered and all appear as intermediate cells.25 or a quinine-HCl (bitter) solution
taste detection and threshold levels as The disruption of the proliferative ca- and correlated with the histological
well as xerostomia. The maximum tol- pacity of the taste cells would cause changes in two groups of nerve fibers
erance dose giving a 50% complica- stem cells to stop dividing, and, once and two groups of taste cells at various
tion rate is approximately 4,000–6,500 the current receptors die off, no new time points after radiation. The nerve
cGy for xerostomia and 5,000–6,500 ones would be there to replace them. fibers followed were labeled with ei-
cGy for taste loss.26 The loss of taste This would be experienced as a loss of ther synaptophysin or CGRP, and the
does not vary by type of radiation (i.e. taste. It does not, however, account for taste cells followed were labeled with
neutron vs. photon radiation).27 the changes in taste measured at 2–3 either NCAM antibodies or B50.
Radiation affects elements of cells days following irradiation in both ani- Briefly, following irradiation, two
that cannot easily be repaired or re- mals and humans. This is more likely changes in the consumption of 1.8%
placed, namely the DNA. As a conse- to be a disruption of the current recep- NaCl are noted: (1) a decrease in the
quence, proliferative cells are most tor cells, possibly via membrane dam- total volume of fluid consumed and (2)
sensitive to the effects of radiation. age causing loss of structural integrity, an increase in the amount of NaCl
Inside the taste buds are the nondivid- or loss of the synaptic contacts. Other consumed. Both of these changes be-
ing nerve fibers and a proliferative possibilities suggested include radia- gin to occur on day 4 (day 0 is the day
population of taste cells. This suggests tion-induced changes in metabolism, the animals received radiation), peakREVIEW THE ANATOMICAL RECORD (NEW ANAT.) 77
at days 7–8, and return to preirradia- will this information impact taste loss a compound is only theoretical at the
tion levels by day 11. The statistical in human cancer patients? Psycho- present.
analysis showed no significant differ- physical measurements of taste acuity In summary, radiation-induced taste
ence prior to radiation between the and taste thresholds have been re- loss is a real problem that has a signifi-
two groups of animals (experimental viewed extensively in the literature cant effect on the treatment of cancer.
and control). Following irradiation, a (see Bartoshuk30) Detection thresh- With information gathered from the
significant difference was seen for the olds are stable over time (M. Linscho- animal model and human studies, we
NaCl consumption on days 7 and 8. ten, personal communication) and can hope to achieve a better understand-
Following the dose of radiation, the be measured using a two alternative ing of the function of the taste system
distribution of the nerve fibers labeled forced choice procedure.31 The pre- and to positively impact the treatment
with synaptophysin or CGRP does not mise is to offer the subject two solu- outcome of cancer patients receiving
change. However, the NCAM-labeled radiation therapy.
tions (one water, one containing a
cells show a dramatic change in ap- tastant) to taste, and the subject
pearance. At 6 days, the NCAM cells chooses which one has a taste differ-
appear normal, with one or possibly ent from water. When the patient can- ACKNOWLEDGMENTS
two cells demonstrating label only in not distinguish between correct and I would like to thank Drs. Mary J.C.
small patches. At day 7 there is a Hendrix, Richard Lynch, and Thomas
incorrect for a given tastant concentra-
dramatic change. Only rare, abnormal- E. Finger for their support and encour-
tion, the patient is believed to be at his
appearing cells labeled with NCAM agement. Also thanks to Jolene Red-
or her threshold for that tastant. As
remain. Also, the rare cells with any vale for review of the manuscript and
patients receive radiation or chemo-
NCAM are also immunoreactive with especially Ken Nelson for the invalu-
therapy, the changes that occur in the
the GAP antibody B50. The normal able assistance with the computer
taste thresholds of any or all of the
pattern of NCAM labeling begins to graphics. The clip art in Figures 1 and
four tastants (sweet, sour, bitter, salty)
return at 11 days, and NCAM-labeled 4 was provided by the Corel Corpora-
cells are more numerous by 16 days. can be followed. It is even possible to
monitor the recovery, or lack thereof, tion.
The change in the pattern of label-
ing for antibody B50 is different from of taste thresholds in these patients
that observed for NCAM. Unlike NCAM over long periods of time.
The purpose of this entire area of LITERATURE CITED
antibody labeling, B50 labeling retains
its normal pattern until 11 days. At study is twofold: to improve on the 1 Kinnamon JC, Taylor BJ, Delay RJ, Roper
this time, the B50-labeled cells begin quality of life of cancer patients receiv- SD (1985) Ultrastructure of mouse vallate
ing radiation therapy and to improve taste buds. I. Taste cells and their associ-
to appear irregular in shape and re- ated synapses. J Comp Neurol 235:48–60.
main so throughout 21 days. Again, the outcome of therapy by maximiz-
2 Kanazawa H, Yoshie S (1996) The taste
the two proteins begin to appear in the ing the patients’ ability to eat and bud and its innervation in the rat as studied
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