Chemical Senses最新文献

Taste perception, initiated by activation of taste receptors in taste bud cells, is crucial for regulating nutrient intake. Genetic polymorphisms in taste receptor genes cannot fully explain the wide individual variations of taste sensitivity. Alternative splicing (AS) is a ubiquitous posttranscriptional mode of gene regulation that enriches the functional diversity of proteins. Here, we report the identification of a novel splicing variant of sweet taste receptor gene Tas1r2 (Tas1r2_∆e4) in mouse taste buds and the mechanism by which it diminishes sweet taste responses in vitro and in vivo. Skipping of Tas1r2 exon 4 in Tas1r2_∆e4 led to loss of amino acids in the extracellular Venus flytrap domain, and the truncated isoform reduced the response of sweet taste receptors (STRs) to all sweet compounds tested by generating nonfunctional T1R2/T1R3 STR heterodimers. The splicing factor PTBP1 (polypyrimidine tract-binding protein 1) promoted Tas1r2_∆e4 generation through binding to a polypyrimidine-rich splicing silencer in Tas1r2 exon 4, thus decreasing STR function and sweet taste perception in mice. Taken together, these data reveal the existence of a regulated AS event in Tas1r2 expression and its effect on sweet taste perception, providing a novel mechanism for modulating taste sensitivity at the posttranscriptional level.

The brain forms robust associations between odors and emotionally salient memories, making odors especially effective at triggering fearful or traumatic memories. Using Pavlovian olfactory fear conditioning (OFC), a variant of the traditional tone-shock paradigm, this study explored the changes involved in its processing. We assessed the expression of neuronal plasticity markers phosphorylated cyclic adenosine monophosphate response element binding protein (pCREB) and phosphorylated mitogen-activated protein kinase (pMAPK) 24 h and 14 days following OFC, in newborn neurons (EdU+) and in brain regions associated with olfactory memory processing; the olfactory bulb, piriform cortex, amygdale, and hippocampus. Here, we show that all proliferating neurons in the dentate gyrus of the hippocampus and glomerular layer of the olfactory bulb were colocalized with pCREB at 24 h and 14 days post-conditioning, and the number of proliferating neurons at both time points were statistically similar. This suggests the occurrence of long-term potentiation within the neurons of this pathway. Finally, OFC significantly increased the density of pCREB- and pMAPK-positive immunoreactive neurons in the medial and cortical subnuclei of the amygdala and the posterior piriform cortex, suggesting their key involvement in its processing. Together, our investigation identifies changes in neuroplasticity within critical neural circuits responsible for olfactory fear memory.

Flavor compounds provide aroma and sensations in the oral cavity. They are not present alone in the oral cavity, but rather in combination with several other food ingredients. This study aimed to clarify the relationship between the mixing of pungent flavor compounds and the response of pungent receptors, TRPV1 and TRPA1 channels. We focused on lactones that activate TRPV1 despite their presence in bland foods, such as dairy products and fruits, and analyzed their interaction with receptors using TRPV1- and TRPA1-expressing HEK293 cells. We found that γ-octalactone, γ-nonalactone, and δ-nonalactone activated TRPA1. When mixed with pungent components, some γ- and δ-lactones inhibited capsaicin-mediated TRPV1 responses, and δ-dodecalactone inhibited allyl isothiocyanate-mediated TRPA1 responses. Furthermore, the dose-response relationship of capsaicin and γ-nonalactone to TRPV1 suggests that γ-nonalactone acts as an agonist or antagonist of TRPV1, depending on its concentration. Conversely, γ-nonalactone and δ-dodecalactone were found to act only as agonists and antagonists, respectively, against TRPA1. These results suggest that lactones in foods may not only endow food with aroma, but also play a role in modulating food pungency by acting on TRPV1 and TRPA1. The dose-response relationships of a mixture of flavor compounds with TRPV1 and TRPA1 provide insights into the molecular physiological basis of pungency that may be the cornerstone for developing new spice mix recipes.

Sensory cells that specialize in transducing olfactory and gustatory stimuli are renewed throughout life and can regenerate after injury unlike their counterparts in the mammalian retina and auditory epithelium. This uncommon capacity for regeneration offers an opportunity to understand mechanisms that promote the recovery of sensory function after taste and smell loss. Immune responses appear to influence degeneration and later regeneration of olfactory sensory neurons and taste receptor cells. Here we review surgical, chemical, and inflammatory injury models and evidence that immune responses promote or deter chemosensory cell regeneration. Macrophage and neutrophil responses to chemosensory receptor injury have been the most widely studied without consensus on their net effects on regeneration. We discuss possible technical and biological reasons for the discrepancy, such as the difference between peripheral and central structures, and suggest directions for progress in understanding immune regulation of chemosensory regeneration. Our mechanistic understanding of immune-chemosensory cell interactions must be expanded before therapies can be developed for recovering the sensation of taste and smell after head injury from traumatic nerve damage and infection. Chemosensory loss leads to decreased quality of life, depression, nutritional challenges, and exposure to environmental dangers highlighting the need for further studies in this area.

Measures of behavioral sensitivity provide an important guide for choosing the stimulus concentrations used in functional experiments. This information is particularly valuable in the olfactory system as the neural representation of an odorant changes with concentration. This study focuses on acetate esters because they are commonly used to survey neural activity in a variety of olfactory regions, probe the behavioral limits of odor discrimination, and assess odor structure-activity relationships in mice. Despite their frequent use, the relative sensitivity of these odorants in mice is not available. Thus, we assayed the ability of C57BL/6J mice to detect seven different acetates (propyl acetate, butyl acetate, pentyl acetate, hexyl acetate, octyl acetate, isobutyl acetate, and isoamyl acetate) using a head-fixed Go/No-Go operant conditioning assay combined with highly reproducible stimulus delivery. To aid in the accessibility and applicability of our data, we have estimated the vapor-phase concentrations of these odorants in five different solvents using a photoionization detector-based approach. The resulting liquid-/vapor-phase equilibrium equations successfully corrected for behavioral sensitivity differences observed in animals tested with the same odorant in different solvents. We found that mice are most sensitive to isobutyl acetate and least sensitive to propyl acetate. These updated measures of sensitivity will hopefully guide experimenters in choosing appropriate stimulus concentrations for experiments using these odorants.

Odor stimuli are widely reported to promote relaxation and reduce anxiety in humans and rodents. However, it remains unclear if this anxiolytic efficacy can be further enhanced by association with positive experiences. Therefore, we compared the effects of a novel odor to a familiar odor previously paired with a positive experience on anxiety-like behaviors in rats. One group of Wistar-Imamichi female and male pups was exposed to an odor stimulus with their dams during postnatal days (PNDs) 8-12, whereas another control group was exposed to perfused air during the same period. Starting on PND 42, all animals were examined in the open field test (OFT) and elevated plus maze (EPM) test during exposure to scent-free air (vehicle), a novel odor, or the positive-familiar odor from postnatal exposure. In the EPM, female rats entered open arms with all 4 paws (complete entry) more frequently and spent more time on open arms during exposure to the positive-familiar odor than during exposure to air or a novel odor, whereas partial open arm entries with forepaws only were increased during exposure to both novel and positive-familiar odors compared to air. In contrast, male rats demonstrated no significant increase in open arm activity during positive-familiar odor exposure, but did show equally reduced grooming frequency during novel and familiar-positive odor exposure in the OFT. Exposure to positive-familiar odors may be an effective and safe method for anxiety reduction, especially in females.

Detection of early and reliable symptoms is important in relation to limiting the spread of an infectious disease. For COVID-19, the most specific symptom is either losing or experiencing reduced olfactory functions. Anecdotal evidence suggests that olfactory dysfunction is also one of the earlier symptoms of COVID-19, but objective measures supporting this notion are currently missing. To determine whether olfactory loss is an early sign of COVID-19, we assessed available longitudinal data from a web-based interface enabling individuals to test their sense of smell by rating the intensity of selected household odors. Individuals continuously used the interface to assess their olfactory functions and at each login, in addition to odor ratings, recorded their symptoms and results from potential COVID-19 test. A total of 205 COVID-19-positive individuals and 156 pseudo-randomly matched control individuals lacking positive test provided longitudinal data which enabled us to assess olfactory functions in relation to their test result date. We found that odor intensity ratings started to decline in the COVID-19 group as early as 6 days prior to the test result date (±1.4 days). Symptoms, such as sore throat, aches, and runny nose appear around the same point in time; however, with a lower predictability of a COVID-19 diagnosis. Our results suggest that olfactory sensitivity loss is an early symptom but does not appear before other related COVID-19 symptoms. Olfactory loss is, however, more predictive of a COVID-19 diagnosis than other early symptoms.

Our goal in this article is to provide a perspective on how to understand the nature of responses to chemical mixtures. In studying responses to mixtures, researchers often identify "mixture interactions"-responses to mixtures that are not accurately predicted from the responses to the mixture's individual components. Critical in these studies is how to predict responses to mixtures and thus to identify a mixture interaction. We explore this issue with a focus on olfaction and on the first level of neural processing-olfactory sensory neurons-although we use examples from taste systems as well and we consider responses beyond sensory neurons, including behavior and psychophysics. We provide a broadly comparative perspective that includes examples from vertebrates and invertebrates, from genetic and nongenetic animal models, and from literature old and new. In the end, we attempt to recommend how to approach these problems, including possible future research directions.

Many widely used psychophysical olfactory tests have limitations that can create barriers to adoption. For example, tests that measure the ability to identify odors may confound sensory performance with memory recall, verbal ability, and prior experience with the odor. Conversely, classic threshold-based tests avoid these issues, but are labor intensive. Additionally, many commercially available tests are slow and may require a trained administrator, making them impractical for use in situations where time is at a premium or self-administration is required. We tested the performance of the Adaptive Olfactory Measure of Threshold (ArOMa-T)-a novel odor detection threshold test that employs an adaptive Bayesian algorithm paired with a disposable odorant delivery card-in a non-clinical sample of individuals (n = 534) at the 2021 Twins Day Festival in Twinsburg, OH. Participants successfully completed the test in under 3 min with a false alarm rate of 7.5% and a test-retest reliability of 0.61. Odor detection thresholds differed by sex (~3.2-fold lower for females) and age (~8.7-fold lower for the youngest versus the oldest age group), consistent with prior studies. In an exploratory analysis, we failed to observe evidence of detection threshold differences between participants who reported a history of COVID-19 and matched controls who did not. We also found evidence for broad-sense heritability of odor detection thresholds. Together, this study suggests the ArOMa-T can determine odor detection thresholds. Additional validation studies are needed to confirm the value of ArOMa-T in clinical or field settings where rapid and portable assessment of olfactory function is needed.