Chemical Senses最新文献

Persistent 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 subject's 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 PLCβ2-dependent taste qualities (sweet, umami, bitter) was significantly more common and was correlated with reduced expression of PLCβ2 and Tas1R3 mRNAs. Histological analysis revealed generally preserved taste bud structure and innervation, but with occasional disorganized taste buds and abnormal, isolated PLCβ2-positive cells in the epithelium. Our findings suggest long-term taste dysfunction after COVID-19 occurs rarely -- more frequently involving PLCβ2-dependent taste qualities -- but is not due to wholesale disruption of the taste periphery.

Post-infectious olfactory dysfunction (PIOD) is common in COVID-19 patients. This two-arm double-blinded randomised controlled trial aimed to establish proof-of-concept for Vitamin A versus placebo as a treatment modality for patients with PIOD. This study compared 9000 IU daily self-administered vitamin A intranasal drops versus peanut oil drops over 12 weeks in COVID-19 patients with PIOD. Outcome measures included: olfactory bulb volume (OBV), olfactory sulcus depth, cerebral functional MRI Blood Oxygen Level Dependent (BOLD) signal, Sniffin' Sticks TDI score, SSParoT, Olfactory Disorder Questionnaire (ODQ) score and Brain Derived Neurotropic Factor (BDNF) levels were collected from participants at baseline and after trial intervention at 12 weeks. Fifty-seven PIOD were recruited in the trial and allocated to Vitamin A or placebo arm at a 2:1 ratio. After withdrawals and exclusions, 30 participants in the Vitamin A arm and 15 in the placebo arm were analysed. There was no significant difference in the change in OBV between both groups. Aside from an improvement in quality-of-life component of ODQ questionnaire scores (p = 0.01), there were no significant differences in any of the other secondary outcome measures. This proof-of-concept trial has demonstrated no significant effect of intranasal Vitamin A on olfactory function in COVID-19 PIOD patients. Further work is required to identify other therapeutic agents in the management of PIOD or evaluate a different PIOD cohort with non-COVID aetiology.

The mechanisms that contribute to CRSwNP-related olfactory loss are poorly characterized. We have previously shown in middle meatus mucus that levels of C3, a component of the complement system, are elevated and correlate with worse disease severity. Excessive complement activation has been shown to impact the severity and progression of injury in the visual and auditory sensory systems but has yet to be investigated in the context of olfaction and thus is the focus of this study. Mucus from the olfactory cleft was sampled from CRSwNP patients (n=22) undergoing endoscopic sinus surgery. Olfactory status was determined by UPSIT. Patients were categorized into two groups: normosmic/mild microsmic (n=10) and moderate microsomia/total anosmia (n=12). Mucus concentrations of classical (C1q), lectin (MBL), alternative pathways (fB, Adipsin), complement proteins (C2, 4, 3, and 5), activation fragments (C4b, C3a, C3b, C5a), and soluble regulators (Factor I and H) were assessed by multiplex or ELISA. With regards to findings, CRSwNP patients with olfactory dysfunction had higher MBL, C4, C3, fB, and Adipsin levels, suggesting lectin and alternative pathway involvement. Complement activation was present and significantly increased in microsomia/total anosmia patients as determined by the presence C3a and C3b complement cleavage fragments. No differences in terminal pathway proteins, C5 or C5a, were noted. Fluid phase complement inhibitor, factor H, was elevated, representative of increased complement activity. In conclusion, Elevated complement activation is linked to more severe olfactory dysfunction. These findings highlight the potential role of complement pathways in the pathogenesis of olfactory impairment related to CRSwNP.

Both poor olfaction and diabetes are common in older adults. It is biologically plausible that they may be related and interact to affect the health of older adults. We examined the association between poor olfaction and diabetes and their joint associations with mortality among 2,416 older adults from the Health, Aging, and Body Composition Study. Olfaction was assessed at year 3 (1999 to 2000) using the Brief Smell Identification Test (B-SIT). We used year 4 (2000 to 2001) as the study baseline and followed participants to year 11 (2007 to 2008) to identify incident diabetes and year 14 (2010 to 2011) to assess mortality. We used logistic regression to analyze the association of poor olfaction with prevalent diabetes and Cox proportional hazard models to assess its relationship to incident diabetes and its joint association with diabetes on mortality. Of the 2,416 participants, 611 (25.3%) had diabetes at baseline and 138 (7.6%) developed incident diabetes during 6.4 ± 1.7 yr of follow-up. Compared to those with good olfaction, the odds ratio of prevalent diabetes was 1.11 (95% confidence interval/CI: 0.87 to 1.42) for those with poor olfaction, and the corresponding hazard ratio (HR) for incident diabetes was 1.01 (95%CI: 0.66 to 1.57). During 8.2 ± 2.8 yr of follow-up, 1007 (41.7%) participants died. Compared with participants without poor olfaction and diabetes, those with both were twice likely to die during the follow-up (HR = 2.16, 95%CI: 1.71 to 2.73). However, we found no evidence for synergistic interaction (P = 0.97). In conclusion, poor olfaction is not associated with the risk of diabetes, and these two conditions independently predict mortality in older adults.

Successful social interactions require the identification of conspecifics and their traits. Often, individuals do not directly interact with conspecifics, but rather with their secretions. Among bodily secretions, urine plays a primary role in social communication across species. Urine provides a wealth of social information, and accordingly, several species, including mice, use it to advertise and mark territories. Here, we asked if kinship relations are reflected by the subject's marking patterns. Specifically, we studied counter-marking patterns of outbred ICR male mice following presentation of urinary cues from conspecifics with varying degrees of kinship. Examination of more than 1000 individual marking patterns from 10 mice reveals a high degree of variability. Variability is apparent across different mice and across single marking bouts of any given individual. Yet, we identify consistent effects of stimulus kinship, and, somewhat unexpectedly, even more robust differences among individuals. Individual-specific marking patterns are also evident in an empty arena, prior to the introduction of an external stimulus. Stimulus presentation gives rise to further changes in marking patterns, reflecting the relationship between the subject and donor mice. Notably, while stimuli representing highly distinct kinship relations induce robust differences at the population level, finer distinctions, including discrimination of same-strain conspecifics and self-urine, are only displayed by a subset of mice. Thus, while counter marking patterns are determined by a variety of factors, some of which cannot be easily controlled or measured, they ultimately reflect the identity of the marker and the kinship relation with the stimulus donor.

Insect-borne diseases kill > 0.5 million people annually. Currently available repellents for personal or household protection are limited in their efficacy, applicability, and safety profile. Here, we describe a machine-learning-driven high-throughput method for the discovery of novel repellent molecules. To achieve this, we digitized a large, historic dataset containing ~19,000 mosquito repellency measurements. We then trained a graph neural network (GNN) to map molecular structure and repellency. We applied this model to select 317 candidate molecules to test in parallelizable behavioral assays, quantifying repellency in multiple insect vectors of the pathogens of disease and in follow-up trials with human volunteers. The GNN approach outperformed a chemoinformatic model and produced a hit rate that increased with training data size, suggesting that both model innovation and novel data collection were integral to predictive accuracy. We identified > 10 molecules with repellency similar to or greater than the most widely used repellents. We analyzed the neural responses from the mosquito antennal (olfactory) lobe to selected repellents and found strong responses to many of the tested compounds, including those predicted to be strong repellents. Results from the antennal lobe recordings also demonstrated a correlation between the evoked responses to strong repellents and our GNN representation. This approach enables computational screening of billions of possible molecules to identify empirically tractable numbers of candidate repellents, leading to accelerated progress towards solving a global health challenge.

Hundreds of bitter substances, synthetic or natural, toxic or health beneficial, chemically complex organic molecules or simple inorganic metal salts, surround us and other vertebrates. Their detection is mediated by bitter taste receptors present in the oral cavity and beyond. The present review article summarizes the current knowledge about these highly versatile receptors in humans and other vertebrates. Following the introductory description of taste anatomy and canonical taste signal transduction, a brief section about bitter compounds provides a flavor of their chemical diversity. The main part of the article is devoted to the human bitter taste receptors, their agonist profiles, structures, and sensitivities. For comparison, a section of bitter taste receptors in other species is added, and, to highlight the functional complexity of these molecules, nongustatory bitter taste receptors and their functions are described.

The ability to discern nutritious food from harmful substances is critical for animal survival, with the gustatory system playing a pivotal role. In insects, including the genetic model Drosophila melanogaster, taste perception involves more than the established valence-based labeled line model, where distinct populations of taste neurons encode appetitive versus aversive stimuli and their activation promotes either attraction or rejection behaviors. A growing body of evidence reveals that sophisticated opponent coding mechanisms operate at multiple levels to modulate responses of taste neurons, enabling dynamic integration between competing taste modalities. These processes significantly expand the informational capacity and behavioral flexibility of the taste system, allowing animals to make appropriate feeding decisions in complex chemical environments where tastants of multiple modalities are simultaneously present.

Animals, including humans, exhibit caution when encountering novel foods, a phenomenon known as food neophobia. This hesitancy decreases with repeated exposures, provided the food is perceived as safe. While extensive research has established rodent models of food neophobia using fluid consumption tasks, studies using solid foods, particularly in mice, are relatively limited. We investigated food neophobia in mice using an olfactory-based task in which the mice were given chow odorized with isoamyl acetate. We quantified several behaviors associated with novelty response and found that the time to begin eating is the most reliable measure of neophobia. Similar levels of neophobia were found using other monomolecular odorants, suggesting that the effect is not odor specific. Further, as some reports of food neophobia in humans have suggested sex differences, we compared food neophobia behaviors in male and female mice. We observed no significant differences between the 2 groups, suggesting that the behavioral expression of food neophobia is similar across sexes. Finally, we found that food neophobia is attenuated upon a second exposure, as mice consume the odorized food as quickly as nonodorized food. Overall, our findings highlight a simple, single-test session approach for exploring olfactory-driven food neophobia.

Gustatory dysfunction (GD), or taste dysfunction, is associated with poor quality of life. Recent literature has demonstrated an association between olfactory dysfunction (OD) and mortality in older adults. However, the association between GD and mortality has not been rigorously studied in a large national cohort. This study helps characterize this relationship and explore underlying mechanisms. Cross-sectional study of the 2013 to 2014 National Health and Nutrition Examination Survey linked to the National Death Index (NDI) through 2019. GD was assessed through self-report and psychometric recognition of quinine and salt, excluding participants with self-reported and psychometric OD. Cox proportional hazards regression models examined associations between GD and mortality, adjusting for demographics, history of cardiovascular comorbidities, diabetes, and malignancy, nutritional status, cognitive function, and depression. Subgroup analysis was also performed based on age and sex. The analytical cohort consisted of 1,136 adults aged 40 and older with complete data, subsequently weighted to create a nationally representative cohort. Isolated psychometric GD is associated with an 87% increased risk of 5-year all-cause mortality after adjusting for all covariates (HR = 1.87, 95% CI = 1.09 to 3.21, P = 0.023). This relationship remains robust among a subgroup of younger participants age 40 to 64 (HR = 18.89, 95% CI = 1.73 to 205.96, P = 0.016) and among male participants (HR = 2.53, 95% CI = 1.34 to 4.76, P = 0.004). Isolated self-reported GD is not statistically significantly associated with mortality. This is one of the first studies to demonstrate an association between GD and mortality, supporting the growing body of literature linking chemosensory dysfunction with unhealthy aging, a finding that warrants more clinical scrutiny.