Brain-derived neurotrophic factor overexpression in taste buds diminishes chemotherapy induced taste loss.

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

Omega 6 polyunsaturated fatty acids in red blood cell membrane are associated with xerostomia and taste loss in patients with breast cancer.

Chemosensory and physical complaints are common disorders in cancer patients under chemotherapy treatments that may affect the food intake, leading to a decreased quality of life. Lipid metabolism is a major pathway of cancer proliferation, where erythrocyte membrane phospholipids and their fatty acid composition are promising tools for monitoring metabolic pathways. Relationship between lipid profile in erythrocyte membrane phospholipids and chemosensory alterations in 44 newly diagnosed patients with breast cancer was here investigated. Smell changes and xerostomia were the most common complaints, with xerostomia as the main influencing factor on the development of other taste disorders. Lipid profiles revealed significant negative correlation between diminution of linoleic acid levels and xerostomia as well as positive correlation between increased arachidonic acid and salty taste. The involvement of these polyunsaturated lipids suggests the importance of oxidative and nutritional conditions of cancer patients, which can affect the molecular status for taste signals.

Possible Use of Phytochemicals for Recovery from COVID-19-Induced Anosmia and Ageusia.

The year 2020 became the year of the outbreak of coronavirus, SARS-CoV-2, which escalated into a worldwide pandemic and continued into 2021. One of the unique symptoms of the SARS-CoV-2 disease, COVID-19, is the loss of chemical senses, i.e., smell and taste. Smell training is one of the methods used in facilitating recovery of the olfactory sense, and it uses essential oils of lemon, rose, clove, and eucalyptus. These essential oils were not selected based on their chemical constituents. Although scientific studies have shown that they improve recovery, there may be better combinations for facilitating recovery. Many phytochemicals have bioactive properties with anti-inflammatory and anti-viral effects. In this review, we describe the chemical compounds with anti- inflammatory and anti-viral effects, and we list the plants that contain these chemical compounds. We expand the review from terpenes to the less volatile flavonoids in order to propose a combination of essential oils and diets that can be used to develop a new taste training method, as there has been no taste training so far. Finally, we discuss the possible use of these in clinical settings.

Gastrointestinal manifestations of COVID-19: results from a European centre.

BACKGROUND: Infection due to severe acute respiratory syndrome coronavirus 2 is typically associated with a respiratory syndrome, but gastrointestinal symptoms have been described in early reports from China. However, data from European centres are scarce. OBJECTIVES: We aimed to characterise the gastrointestinal manifestations of patients with coronavirus disease 2019 (COVID-19) and their disease course. METHODS: Patients admitted at our centre between March and April 2020 with diagnosis of COVID-19 were included. Asymptomatic patients or those without symptom information were excluded. Clinical features, laboratory data and disease severity (mechanical ventilation, intensive care admission or death) were analysed. RESULTS: Two-hundred one patients were included (median age 71 years; 56.2% male). Digestive symptoms were reported by 60 (29.9%) patients during the disease course, being part of the disease presentation in 34 (16.9%). The most frequent were diarrhoea in 36 patients (17.9%). Patients with gastrointestinal symptoms were younger (P = 0.032), had higher haemoglobin levels (P = 0.002) and lower C-reactive protein (P = 0.045) and potassium levels (P = 0.004). Patients with digestive symptoms had less severe disease (28.3 vs. 44.0%; P = 0.038). Regarding liver damage, aspartate aminotransferase (AST) was elevated in 65.2% of patients and alanine aminotransferase (ALT) in 62.7%, but these patients did not present a more severe disease (elevated AST P = 0.062; elevated ALT P = 0.276). CONCLUSION: A significant portion of COVID-19 patients have digestive symptoms, mostly at presentation. This should be taken into account in order to keep a high level of suspicion to reach an early diagnosis and setup infection control measures to control the transmission rate. This subgroup of patients appears to have a less severe disease course.

Pathogenesis of dysgeusia in COVID-19 patients: a scoping review.

OBJECTIVE: The novel coronavirus disease-19 (COVID-19) pandemic had intense social and economic effects. Patients infected with COVID-19 may present with a series of conditions. A considerable number of patients express taste and smell disturbances as a prodromal, coexistent, or as the only manifestation of COVID-19 infection. The objective of the present review is to review the hypothetical mechanisms of action and etiopathogenesis of dysgeusia in COVID-19 patients. MATERIALS AND METHODS: Multiple scientific databases were explored, including PubMed, Medline, Scopus, Cochrane-library, LILACS, Livivo and OpenGrey. All types of articles that discussed the pathogenesis of dysgeusia were included, while articles that described dysgeusia without detail about its mode of action were excluded. RESULTS: A total of 47 articles, with different designs, were included in this review. These articles suggested direct viral neural invasion to olfactory and gustatory nerves, viral cytotoxicity to taste buds, angiotensin II imbalance, augmented pro-inflammatory cytokines, and disturbances in salivary glands and sialic acid. COVID-19 induced-dysgeusia was also associated with systemic diseases, medications, zinc, chemicals, and disinfectants. CONCLUSIONS: The most likely cause of transient dysgeusia in COVID-19 is peripheral neurotropism and direct toxicity to taste buds or olfactory epithelium. Other factors may also play a contributory role in dysgeusia, such as a defect in the quality and quantity of saliva, pro-inflammatory cytokines, angiotensin II accumulation, systemic diseases, hypozincemia, and excessive use of chemicals.

Loss of sweet taste despite the conservation of sweet receptor genes in insectivorous bats.

The evolution of taste perception is usually associated with the ecology and dietary changes of organisms. However, the association between feeding ecology and taste receptor evolution is unclear in some lineages of vertebrate animals. One example is the sweet taste receptor gene Tas1r2 Previous analysis of partial sequences has revealed that Tas1r2 has undergone equally strong purifying selection between insectivorous and frugivorous bats. To test whether the sweet taste function is also important in bats with contrasting diets, we examined the complete coding sequences of both sweet taste receptor genes (Tas1r2 and Tas1r3) in 34 representative bat species. Although these two genes are highly conserved between frugivorous and insectivorous bats at the sequence level, our behavioral experiments revealed that an insectivorous bat (Myotis ricketti) showed no preference for natural sugars, whereas the frugivorous species (Rousettus leschenaultii) showed strong preferences for sucrose and fructose. Furthermore, while both sweet taste receptor genes are expressed in the taste tissue of insectivorous and frugivorous bats, our cell-based assays revealed striking functional divergence: the sweet taste receptors of frugivorous bats are able to respond to natural sugars whereas those of insectivorous bats are not, which is consistent with the behavioral preference tests, suggesting that functional evolution of sweet taste receptors is closely related to diet. This comprehensive study suggests that using sequence conservation alone could be misleading in inferring protein and physiological function and highlights the power of combining behavioral experiments, expression analysis, and functional assays in molecular evolutionary studies.

Depletion of bitter taste transduction leads to massive spermatid loss in transgenic mice.

Bitter taste perception is an important sensory input warning against the ingestion of toxic and noxious substances. Bitter receptors, a family of ~30 highly divergent G-protein-coupled receptors, are exclusively expressed in taste receptor cells that contain the G-protein α-subunit gustducin, bind to α-gustducin in vitro, and respond to bitter tastes in functional expression assays. We generated a taste receptor type 2 member 5 (T2R5)-Cre/green fluorescent protein reporter transgenic mouse to investigate the tissue distribution of T2R5. Our results showed that Cre gene expression in these mice was faithful to the expression of T2R5 in taste tissue. More surprisingly, immunostaining and X-gal staining revealed T2R5 expression in the testis. Ablation of T2R5 + cells led to a smaller testis and removed the spermatid phase from most of the seminiferous tubules. The entire taste transduction cascade (α-gustducin, Ggamma13, phospholipase Cß2) was detected in spermatogenesis, whereas transient receptor potential, cation channel subfamily M member 5 (Trpm5), was observed only in the later spermatid phase. In short, our results indicate that the taste transduction cascade may be involved in spermatogenesis.

Construction of a taste-blind medaka fish and quantitative assay of its preference-aversion behavior.

In vertebrates, the taste system provides information used in the regulation of food ingestion. In mammals, each cell group within the taste buds expresses either the T1R or the T2R taste receptor for preference-aversion discrimination. However, no such information is available regarding fish. We developed a novel system for quantitatively assaying taste preference-aversion in medaka fish. In this study, we prepared fluorescently labeled foods with fine cavities designed to retain tastants until they were bitten by the fish. The subjects were fed food containing a mixture of amino acids and inosine monophosphate (AN food), denatonium benzoate (DN food) or no tastant (NT food), and the amounts of ingested food were measured by fluorescence microscopy. Statistical analysis of the fluorescence intensities yielded quantitative measurements of AN food preference and DN food aversion. We then generated a transgenic fish expressing dominant-negative Galpha(i2) both in T1R-expressing and in T2R-expressing cells. The feeding assay revealed that the transgenic fish was unable to show a preference for AN food and an aversion to DN food. The assay system was useful for evaluating taste-blind behaviors, and the results indicate that the two taste signaling pathways conveying preferable and aversive taste information are conserved in fish as well as in mammals.

Brain gamma-aminobutyric acid levels are decreased in patients with phantageusia and phantosmia demonstrated by magnetic resonance spectroscopy.

BACKGROUND: Olfactory and gustatory hallucinations (phantosmias and phantageusias, respectively) are sensory distortions that commonly follow losses of olfactory and gustatory acuity (hyposmia and hypogeusia, respectively). The biochemical basis of these hallucinations is unclear. Functional magnetic resonance imaging has been used previously to demonstrate widespread and robust central nervous system (CNS) activation to memories of these sensory distortions in patients with these symptoms. In this study, possible CNS mechanisms responsible for these distortions were evaluated using magnetic resonance spectroscopy, because this technique has been used to measure various CNS metabolites in patients with neurologic disorders. METHODS: Forty-seven subjects were studied: 28 normal volunteers (13 men and 15 women) and 19 patients (8 men and 11 women) with persistent oral global phantageusia and/or birhinal phantosmia studied before any treatment. Four patients (1 man and 3 women) were studied before and after pharmacologic treatment that reduced the severity of their sensory distortions. All subjects were studied in a Signa 1.5-T magnetic resonance scanner with a quadrature head coil using a modified standard 2-dimensional J-point resolved excitation in the steady state (PRESS) sequence by which gamma-aminobutyric acid (GABA), glutamic acid, choline, N-acetylaspartate, and creatine (Cre) were measured in various CNS regions. Results were expressed using Cre as a denominator to determine ratios for each measurement. Differences were defined between normal subjects and patients before treatment and in patients before and after successful pharmacologic treatment. RESULTS: Before treatment, GABA levels in several CNS regions were lower in patients than in normal volunteers and were the only biochemical changes found; significantly lowered GABA levels were found in the cingulate, right and left insula, and left amygdala. No differences between patients and normal volunteers were found in any of the metabolites in the posterior occipital region. After treatment that inhibited sensory distortions, CNS GABA levels increased in the cingulate, insula, and amygdala but significantly only in the left insula and in the right and left amygdala. After this successful treatment, no change in any biochemical parameter was found in the posterior occipital region. CONCLUSIONS: These results indicate that decreased brain GABA levels can serve as biochemical markers of phantageusia and/or phantosmia in patients with these distortions and are the first biochemical changes in the CNS that reflect these sensory changes. After successful treatment of these distortions, CNS GABA levels increased to levels at or near normal, consistent with functional remission of these symptoms. These results substantiate a role for CNS GABA in the generation and inhibition of these sensory hallucinations. Although the underlying biochemical mechanism(s) for the generation of these decreased GABA levels are complex, because similar types of sensory hallucinations occur as auras or prodromata of epileptic seizure and migraine activity, these results suggest that there may be common biochemical changes among these disorders.

A histochemical study of APUD ability in the taste buds of experimentally induced zinc-deficient mice.

To explore the relationship between taste acuity and zinc deficiency, a histochemical investigation was made into the taste buds of mice fed a zinc-deficient diet. Nine weeks after the start of the diet, the average serum zinc level of the mice was 45% lower than that of a control group of mice. Moreover, growth was arrested significantly. Two-bottle preference tests revealed that the intake ratio of 10(-5) M quinine hydrochloride solutions had increased markedly in the zinc-deficient mice compared with the controls. The circumvallate taste buds showed no morphological changes. Fluorescent histochemical examination showed an uptake of a monoamine precursor (5-HTP) by the gustatory cells in the zinc-deficient mice after the 5-HTP treatment. Upon immunohistological examination, however, no serotonin immunoreactivity appeared in the gustatory cells of the zinc-deficient mice after the 5-HTP treatment. These results suggest that zinc-deficiency may induce hypogeusia and decrease the ability to transform a monoamine precursor to monoamine in the gustatory cells, albeit the monoamine precursor uptake ability is not affected.

Estimation of zinc concentration of parotid saliva by flameless atomic absorption spectrophotometry in normal subjects and in patients with idiopathic hypogeusia.

The concentraiton of zinc in parotid saliva was estimated by flameless atomic absorption spectrophotometry. As small a sample as 5 to 10 mul of whole paratid saliva can be analyzed quickly and reliably, without special sample handling and with littleinterference from other ions normally found in saliva. Parotid salivary zinc concentration in 34 subjects with normal taste acuity was 51 plus or minus 14 ppb(parts per billion)(mean plus or minus 1 S.D.); parotid salivary zinc concentration in 47 subjectswith idiopathic hypogeusia was 10 plus or minus 6 ppb (mean plus or minus 1 S.D.) which is significantly lower than that in normal subjects (p lessthan 0.001). This technique is a usual method by which to evaluate parotid salivary zinc, particulary inrelationship to problems of taste, appetite, and nutrition.