Chemical Senses最新文献

Eating behavior is shaped by genetic, psychological, and physiological factors, with nutrient sensing playing a central role in modulating intake. The tongue, as the primary gustatory organ, initiates this process by influencing hedonic preferences, food choices, and feeding behavior. Recent sensory research has highlighted the potential role of an emerging class of taste modalities known as alimentary tastes. This concept refers to the gustatory detection of compounds that produce weak or subtle taste perceptions but elicit strong postoral effects. While most studies have focused on umami and fat taste in that category, growing interest surrounds newly characterized modalities such as kokumi- and complex carbohydrate-associated tastes. Basic and alimentary taste stimulus influence behavior and physiological processes both pre- and postingestion. Their receptors, present in enteroendocrine cells, detect specific nutrients and regulate gut feedback mechanisms. Emerging research is investigating not only their involvement in metabolic disorders and conditions such as malnutrition, but also their potential as therapeutic targets for modulating appetite, nutrient absorption, and endocrine responses. This narrative review aims to identify and characterize the functions of these postoral receptors along the gastrointestinal tract in the regulation of food intake and to evaluate their therapeutic potential in metabolic conditions such as obesity and type 2 diabetes.

Enzymes exemplify the adaptability of biological systems through their multifunctional roles across tissues. Thus, xenobiotic metabolizing enzymes, traditionally recognized for their contributions to detoxification, biosynthesis, and signaling, also play specialized roles in the nasal cavity, where they encounter volatile compounds on a daily basis. In olfactory tissues, xenobiotic metabolizing enzymes act as odorant metabolizing enzymes, influencing not only volatile xenobiotic clearance but also sensory perception. These enzymes operate within a coordinated network of phase I, II, and III reactions, and are distributed across epithelial and neuronal cell types in both the olfactory and respiratory regions of the nasal cavity. Their expression patterns, activity, and regulatory dynamics suggest that xenobiotic metabolism can modulate olfactory function, with potential implications for toxicity, protection, and sensory modulation. This review first considers the risks posed by airborne xenobiotics and their impact on olfaction, then examines the function, expression, and regulation of odorant metabolizing enzymes, and finally highlights current experimental models and methodological advances that provide insights into xenobiotic and odorant metabolism in the nasal cavity.

Odors are often considered to be powerful memory cues, yet early olfactory paired-associate (PA) studies suggested that they are less effective than other sensory cues and particularly prone to proactive interference (PI). Research with other modalities indicates semantic similarity increases retroactive interference (RI). Two experiments compared olfactory PA memory to verbal and auditory PA memory, focusing on the role of semantic congruency. In Experiment 1, a mixed design tested the efficiency of odors as a PA cue under semantically congruent versus incongruent conditions. One hundred one participants were randomly assigned to 4 groups, each experiencing one of the following cross-modal pairs: olfactory-visual and verbal-visual (as a control group for olfactory-visual), auditory-visual, and verbal-visual (as a control group for auditory-visual). Replicating prior work, odors were less effective than verbal or auditory cues. However, semantic congruency enhanced performance across modalities, with a greater effect for olfactory PAs. Experiment 2 employed a mixed design to assess PI and RI in olfactory versus verbal PA memory. Thirty-eight participants were randomly assigned to one of two cross-modal pair groups (olfactory-visual and verbal-visual). RI was more pronounced than PI for both modalities, with RI levels increasing when the second pair of associations was semantically congruent, but the first was not. Semantic congruency consistently enhanced olfactory retrieval cues, supporting its role in mitigating interference effects. These findings demonstrate that while odors are less effective associative cues than verbal or auditory stimuli, semantic congruency significantly improves their utility, highlighting the nuanced interplay between modality and memory processes.

We investigated the effects of coding single-nucleotide polymorphisms (SNPs) in bitter taste receptors TAS2R43 and TAS2R46 on their predicted structural stability, cellular functions, and human threshold for bitterness of caffeine. We found differences in the cell surface expression and reaction to caffeine among the haplotypes of TAS2R43 and -46 protein. Ancestral haplotypes of the proteins showed higher response to caffeine than derived haplotypes both for TAS2R43 and -46, which were also predicted to be less structurally stable and showed lower expression at the cell surface membrane. There was a significant difference in human bitter perception of caffeine between people with different TAS2R43 genotypes. Considering the functional differences based on their genotypes and the distribution of the haplotypes in the regions, these SNPs may relate to the sensitivity to several bitter compounds, which correlated with human evolution spread from Africa.

Olfactory perception, mediated by G protein-coupled receptors (GPCRs) such as odorant receptors (ORs) and trace amine-associated receptors (TAARs), plays a pivotal role in human health, influencing behaviors like food choices and serving as early biomarkers for neurodegenerative diseases. Despite their importance, olfactory GPCRs are among the least understood members of the GPCR superfamily, and most ORs and TAARs are still orphan receptors. This review provides a comprehensive overview of recent advancements in the structural bioinformatics of olfactory GPCRs. We outline how computational, structure-based strategies have succeeded in identifying novel modulators for olfactory receptors. By discussing recent breakthroughs in GPCR structural biology, such as the first resolved experimental structures of ORs and TAARs, and the transformative impact of AI-driven structure prediction tools for olfactory receptors, this review offers a roadmap for future olfaction pharmacology research.

Mechanosensory neurons play a crucial role in determining the location of stimuli on the receptor surface, movement, as well as the identification and discrimination of textures. To date, little is known about mechanosensory neuron types that innervate the oral cavity. Here, we recorded from mechanosensitive neurons innervating the oral cavity, to examine their diversity and function mediating touch. We first recorded a rough topographical map to aid in locating mechanosensory neuron types innervating the oral cavity. Electrophysiological mapping indicated that neurons innervating the tongue were located within and between maxillary (V2) and mandibular (V3) receptive fields, resembling a "strip" similar to the anatomical position of the tongue. We found that both rapidly adapting and slowly adapting neurons innervate the anterior tongue and lips. Conduction velocity experiments showed that all the lip-innervating neurons were classified as C-fibers, whereas there was a broader range for the tongue-innervating neurons, ranging from C-fibers to A-fast. Interestingly, we found that rapidly adapting and slowly adapting neurons were present at all 3 conduction velocity classifications. The majority of pressure-sensitive neurons also responded to brush stimulation (91%); however, there was a small subset of neurons that only responded to pressure stimulation (9%). The majority of the A-fibers had receptive fields on the anterior tip of the tongue. Furthermore, we found that when a mechanically sensitive neuron innervated a fungiform papilla, its receptive field did not include the surrounding filiform papillae. Our findings provide important contributions to understanding some of the coding features of mechanosensory neurons that innervate the oral cavity.

Early childhood is a critical developmental period for the establishment of flavor preferences that in turn affect food and beverage consumption and health into adulthood. Flavor is a multisensory experience, combining taste and retronasal odor signals. However, while early life development of taste perception has received ample attention, there is limited knowledge of retronasal odor perception in early life. In the present cross-sectional study, we tested the hypothesis that hedonic perception of retronasal smell differs between children and adults. We used video analysis of facial expressions to taste and retronasal odor solutions in children and adults. Children ages 3 to 6 and one of their parents (n = 112 dyads) were asked to sample solutions containing either a taste or an odor compound. A subset of subjects (n = 84 dyads) also explicitly rated each solution on a pictorial liking scale. No differences between the 2 age groups were observed in responses to taste solutions. In contrast, responses to retronasal odor stimuli were less stimulus-specific in children compared with adults. Children showed fewer negative facial expressions to broccoli and pumpkin odors, and more negative facial expressions to apple and mango odors. Similar differences between the 2 age groups were observed in explicit hedonic ratings. These findings support our hypothesis that the hedonic value of retronasal odor components of flavor is not innate but differ between young children and adults.

In cancer chemotherapy, the development of taste disorders is a serious problem because it not only reduces quality of life but also deteriorates patients' nutritional status, sometimes resulting in cessation of chemotherapy. Doxorubicin (DOX), a widely used anticancer anthracycline, reportedly alters patients' taste perception. However, little information exists on the detailed characteristics of DOX-induced taste disorders. In this study, we investigated whether taste responsiveness was altered in DOX-administered mice using a brief-access test and examined the underlying mechanisms. DOX-administered mice exhibited decreased responsiveness to sweet taste, but not to umami, bitter, salty, or sour tastes, on day 7, with recovery by day 14. Although there was no detectable alteration in the number of type II-taste cell marker-immunoreactive cells in the circumvallate papillae (CP), expression of mRNA for sweet taste receptors T1R2, T1R3, and α-gustducin in the CP was greater in DOX-administered mice than in control mice on day 7. Interestingly, in DOX-administered mice on day 7, the lick ratios for a 300-mM sucrose solution showed a significant correlation with the relative expression of T1R3 mRNA in the CP and a trend toward a correlation with food consumption. Together, these findings suggest that the decrease in sweet taste sensitivity in DOX-administered mice might result from dysfunction in signaling downstream of taste perception, with increased sweet taste receptor expression potentially representing a compensatory response to decreased energy intake.

Olfactory training (OT), a structured exposure to odors, is commonly used by otorhinolaryngologists to treat olfactory dysfunction. However, OT has been shown to improve cognition of people with cognitive or olfactory impairments and slow the age-related cognitive decline. This study investigated whether OT could enhance cognitive functions in older adults with an intact sense of smell, compared with younger adults. We hypothesized that OT would improve semantic verbal fluency and working memory in the experimental group, with no significant changes in the placebo group (PG). The final sample comprised 184 participants aged 24 to 94 years (Mage = 51.84 ± 23.25 years), including 83 young adults (53% women, Mage = 26.71 ± 2.62 years) and 101 older adults (88% women, Mage = 72.49 ± 5.40 years). For the semantic verbal fluency task, they listed as many items as possible within one of 2 semantic categories: (i) grocery products or (ii) fragrant items, within a 60-s time limit. To measure working memory, participants completed a digit span task where they repeated sequences of digits aloud. In older adults performing OT, it led to a marginal increase in semantic verbal fluency, regardless of semantic category, while no significant changes were observed in the older PG or in young adults. This effect was mainly driven by individuals with lower scores at baseline. Our findings suggest that OT can benefit semantic verbal fluency in the healthy geriatric population with lower baseline scores, but these results urge similar testing in clinical groups with compromised verbal functions.

Although animals can reliably locate and recognize odorants embedded in complex environments, the neural circuits for accomplishing these tasks remain incompletely understood. Adaptation is likely to be important as it could allow neurons in a brain area to adjust to the broader sensory environment. Adaptive processes must be flexible enough to allow the brain to make dynamic adjustments, while maintaining sufficient stability so that organisms do not forget important olfactory associations. Processing within the mouse olfactory bulb is likely involved in generating adaptation, although there are conflicting models of how it transforms the glomerular output of the mouse olfactory bulb. Here we performed 2-photon Ca2+ imaging from mitral/tufted glomeruli in awake mice to determine the time course of recovery from adaptation, and whether it acts broadly or selectively across the glomerular population. Individual glomerular responses, as well as the overall population odor representation were similar across imaging sessions. However, odor-concentration pairings presented with interstimulus intervals upwards of 30-s evoked heterogeneous adaptation that was concentration-dependent. We demonstrate that this form of adaptation is unrelated to variations in respiration, and olfactory receptor neuron glomerular measurements indicate that it is unlikely to be inherited from the periphery. Our results indicate that the olfactory bulb output can reliably transmit stable odor representations, but recent odor experiences can selectively shape neural responsiveness for upwards of 30 seconds. We propose that neural circuits that allow for non-uniform adaptation across mitral/tufted glomeruli could be important for making dynamic adjustments in complex odor environments.