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Acute anosmia in the mouse: behavioral discrimination among the four basic taste substances.

The importance of taste and smell in discrimination of tastes was examined in normal and anosmic mice. We studied the influence of olfaction on taste sensation using behavioral and electrophysiological methods in both normal animals and animals made anosmic mice by destroying their olfactory receptor cells with zinc sulfate (ZnSO(4)) solution. Electrophysiological responses from chorda tympani nerves showed that peripheral taste receptor cells transmitted taste signals normally to the central nervous system, even when the olfactory senses were abnormal. Behavioral observations showed that mice with abnormal olfaction could not differentiate tastes.

Animals↗

Olfactory dysfunction in humans with deficient guanine nucleotide-binding protein.

The guanine nucleotide-binding stimulatory protein (Gs) couples hormone-receptor interaction to the activation of adenylate cyclase and the generation of cyclic AMP. Studies using frog neuroepithelium indicate that the sense of smell is mediated by a Gs-adenylate cyclase system, and this prompted us to test olfaction in the only known model of Gs deficiency in the animal kingdom, Gs-deficient (type 1a) pseudohypoparathyroidism (PHP), which occurs in humans. Such patients are resistant to the cAMP-mediated actions of several hormones. (Although Henkin has reported disturbances in the sense of smell in six patients with PHP, currently available biochemical measurements such as the cAMP response to parathyroid hormone (PTH) and determination of Gs activity were not reported and olfactory testing was limited.) In the present study, we found that all Gs-deficient patients had impaired olfaction when compared with PHP patients who had normal Gs activity (type 1b PHP, in which patients are resistant only to the action of PTH in the kidney). This is the first evidence of human olfactory impairment which can be related to Gs deficiency and suggests that Gs-deficient PHP patients may be resistant to cAMP-mediated actions in other non-endocrine systems.

Cyclic AMP↗

Impaired sense of smell in patients with nasal surgery.

The aim of the study was to determine the incidence of olfactory disorders before and following nasal and paranasal sinus surgery. It was a prospective observational study. Over a 6-month period, all patients who had been listed for nasal and paranasal sinus surgery underwent preoperative and postoperative evaluation of their sense of smell. A questionnaire and the 'Smell Diskettes Test' were used to assess olfaction. One hundred and eighty-four patients were studied. Preoperatively, 19 patients (10.3%) had an impaired sense of smell (8.1% before septoplasty, 6.1% before rhinoplasty and 17.1% before endoscopic sinus surgery). Only 16 (84%) of these patients were aware of their impaired sense of smell. Following surgery, four patients (2.5%) who were normal preoperatively developed impaired olfaction on questioning, and this was supported by testing it. In the subgroup that had a septoplasty, no patient developed hyposmia compared to one patient (2.6%) after rhinoplasty and one patient (3%) after endoscopic sinus surgery. No patient developed anosmia. Preoperatively, 10.3% of patients had an altered sense of smell, making it desirable that this is documented in order to avoid postoperative claims that this was caused by surgery. It also helps to audit the results of surgery.

Female↗

An impairment in sniffing contributes to the olfactory impairment in Parkinson's disease.

Although the presence of an olfactory impairment in Parkinson's disease (PD) has been recognized for 25 years, its cause remains unclear. Here we suggest a contributing factor to this impairment, namely, that PD impairs active sniffing of odorants. We tested 10 men and 10 women with clinically typical PD, and 20 age- and gender-matched healthy controls, in four olfactory tasks: (i) the University of Pennsylvania smell identification test; (ii and iii) detection threshold tests for the odorants vanillin and propionic acid; and (iv) a two-alternative forced-choice detection paradigm during which sniff parameters (airflow peak rate, mean rate, volume, and duration) were recorded with a pneomatotachograph-coupled spirometer. An additional experiment tested the effect of intentionally increasing sniff vigor on olfactory performance in 20 additional patients. PD patients were significantly impaired in olfactory identification (P < 0.0001) and detection (P < 0.007). As predicted, PD patients were also significantly impaired at sniffing, demonstrating significantly reduced sniff airflow rate (P < 0.01) and volume (P < 0.002). Furthermore, a patient's ability to sniff predicted his or her performance on olfactory tasks, i.e., the more poorly patients sniffed, the worse their performance on olfaction tests (P < 0.009). Finally, increasing sniff vigor improved olfactory performance in those patients whose baseline performance had been poorest (P < 0.05). These findings implicate a sniffing impairment as a component of the olfactory impairment in PD and further depict sniffing as an important component of human olfaction.

Adult↗

Social evolution and diminished olfactory function in larval honey bees.

Social evolution made larval honey bees dependent on adult colony members for feeding; they are confined to cells in waxen honeycombs and visited about 100 times per day by adult "nurse" bees. Based on organismal resource conservation theory, we predicted larvae have diminished olfactory capabilities at both the molecular and behavioral levels. Consistent with theory, larvae expressed very low levels of Orco, an essential gene for olfactory receptor (OR) function. By contrast, they showed higher expression of Ir25a, essential for other forms of sensory perception including gustation. Also consistent with theory, behavioral assays demonstrated that larvae cannot find food via olfaction, suggesting they use taste for feeding. By contrast, it is known that adult honey bees use OR-based olfaction extensively for a variety of behavioral functions, and the honey bee genome contains many OR-encoding genes. Comparative transcriptomic analyses of social and nonsocial insects suggest that this developmentally regulated suppression of olfactory function is related to social evolution, especially systems of offspring care.

Animals↗

Correspondence between three olfactory tests and suprathreshold odor intensity ratings.

OBJECTIVES: The capability of three olfactory tests (European Test of Olfactory Capabilities, Sniffin' Sticks and Cross-Cultural Smell Identification Test) to similarly classify subjects as normosmics, hyposmics and anosmics as well as the relation between test performance and suprathreshold ortho- and retronasal odor intensity ratings were examined. MATERIAL AND METHODS: A total of 48 subjects (age range 15-84 years; mean age 49.5 years) completed the 3 olfactory tests, rated aqueous solutions of vanilla (0-0.31%) and lemon aroma (0-0.17%) for odor and flavor intensity and filled in a background questionnaire. Ten subjects had case histories indicating anosmia, with the remainder having subjectively normal olfaction. RESULTS: The test results were highly correlated and differentiated anosmic, hyposmic and normosmic subjects. At an individual level, some discrepancy was seen in the olfactory diagnoses given by the three tests. In principal component analysis, olfactory measurements were loaded on three components: (i) odor detection, discrimination and identification; (ii) suprathreshold intensity ratings; and (iii) threshold for n-butanol. Advanced age was related to impaired olfactory performance. CONCLUSIONS: Although the three olfactory tests diagnosed the individuals slightly differently, all were considered to be valid for clinical evaluation of olfactory capabilities. The tests separated anosmics and normosmics highly significantly, and permitted an assessment of hyposmia. The suprathreshold odor intensity ratings reflected a different dimension of olfaction than the three olfactory tests.

Adolescent↗

Screening of olfactory function using the Biolfa olfactory test: investigations in patients with dysosmia.

OBJECTIVE: To present a statistical evaluation of a new olfactory test, Biolfa. MATERIAL AND METHODS: The olfactory test was carried out in individuals with normal olfactory function (n=67; 31 males; mean age 27.4 years) and in patients with mild, moderate or severe hyposmia (n=155; 61 males; mean age 54.6 years). The main diagnoses of the hyposmic patients were upper respiratory tract infection (32%), nasal polyposis (24%), head trauma (8%), idiopathic (8%), old age (5%) and chronic rhinitis (5%). In the first part of the test, olfactory thresholds were measured for three different substances (eugenol, aldehyde C14 and phenyl ethyl alcohol). The second part comprised an odor identification test for determining olfactory function for a large panel of common odors of Southern European countries. RESULTS: Mean olfactory thresholds were determined for subjects with normal olfaction and hyposmic patients; there was a statistically significant relationship between olfactory thresholds and degree of olfaction (mild to moderate hyposmia versus severe hyposmia). For the odor identification test, a global score was determined to allow the differentiation of normosmic subjects from patients with mild, moderate or severe hyposmia. The principles of decision theory (i.e. analysis of the receiver operating characteristic curve) were applied to the problem of evaluating the ability of Biolfa to distinguish subnormal subjects from hyposmic subjects. CONCLUSION: This study provides a basis for the routine clinical use of Biolfa.

Adult↗

Olfactory testing: rules for odor identification.

Neurology manuals generally recommend odor identification for simple assessment of olfaction. Nevertheless, even patients with normal olfaction (normosmics) often perform only poorly. Three experiments demonstrate that such an ambiguous outcome will disappear if the test incorporates highly familiar substances and, more important, a procedure to circumvent the olfactory-verbal gap that frequently separates an odor from its name. One multiple-choice procedure, for instance, led to 100% accuracy among normosmics. Another led to 99% accuracy among normosmics and 0% accuracy among anosmics. The investigation also reveals that scratch-and-sniff labels could possibly replace customary odorants in the clinical test.

Adult↗

The minimum number of neurons in the central olfactory pathway in relation to its function: a retrograde fiber tracing study.

The present study was aimed at determining the functionally essential size of the neuronal population in the central olfactory nervous system. Using conditioned rats who had learnt to avoid repellent (cycloheximide) solution by olfaction, varying degrees of injuries were made to the lateral olfactory tract, a major central olfactory pathway connecting the olfactory bulb to the olfactory cortex. After examining their olfactory ability to discriminate cycloheximide solution from water, intact bulbar projection neurons (mitral cells) with fiber connections to the olfactory cortex were quantified using a retrograde fiber tracing technique. The numbers of retrogradely labeled mitral cells from the rats with normal olfaction ranged between 20 and 92% of the control value, while those numbers from the anosmic rats ranged between 0 and 22%. We conclude that the functionally essential neuronal population is approximately one-fifth of the total in the central olfactory pathway, a presumed threshold value in terms of the ability to avoid cycloheximide solution by olfactory discrimination.

Animals↗

Longitudinal changes in smell identification.

BACKGROUND: Cross-sectional studies have demonstrated that olfactory function diminishes with increasing age, which may impact on the safety and quality of life of older persons. To date, however, there have been no published longitudinal studies on olfaction. The purpose of this study was to examine the influence of age and gender on smell identification over a 3-year period in a group of generally healthy men and women. METHODS: Males (n = 85) and females (n = 76) between the ages of 19 and 95 years were administered the University of Pennsylvania Smell Identification Test (SIT) over a 3-year span as part of the oral physiology component of the Baltimore Longitudinal Study of Aging. A linear mixed-effects regression model was used to determine how longitudinal changes in SIT scores differ with respect to gender, history of medical problems, and use of prescription medications. RESULTS: Over the 3-year period, SIT scores diminished progressively with increased age. Women and men in the eighth decade of life experienced a decline of greater than one SIT point per year. Females consistently performed better than males in smell identification. Similar results were obtained regardless of medical problems or medication usage. CONCLUSIONS: These results extend the conclusions of previous cross-sectional olfactory studies and indicate that smell identification deteriorates progressively with greater age. Furthermore, age-related declines in olfaction occur even in the absence of overt medical problems.

Adult↗

Evolutionary Process Underlying Receptor Gene Expansion and Cellular Divergence of Olfactory Sensory Neurons in Honeybees.

Olfaction is crucial for animals' survival and adaptation. Unlike the strict singular expression of odorant receptor (OR) genes in vertebrate olfactory sensory neurons (OSNs), insects exhibit complex OR gene expression patterns. In honeybees (Apis mellifera), a significant expansion of OR genes implies a selection preference for the olfactory demands of social insects. However, the mechanisms underlying receptor expression specificity and their contribution to OSN divergence remain unclear. In this study, we used single-nucleus multiomics profiling to investigate the transcriptional regulation of OR genes and the cellular identity of OSNs in A. mellifera. We identified three distinct OR expression patterns, singular OR expression, co-expression of multiple OR genes with a single active promoter, and co-expression of multiple OR genes with multiple active promoters. Notably, &#x223c;50% of OSNs co-expressed multiple OR genes, driven by polycistronic transcription of tandemly duplicated OR genes via a single active promoter. In these OSNs, their identity was determined by the first transcribed receptor. The divergent activation of the promoter for duplicated OR genes ensures the coordinated increased divergence of OSN population. By integrating multiomics data with genomic architecture, we illustrate how fundamental genetic mechanisms drive OR gene expansion and influence flanking regulatory elements, ultimately contributing to the cellular divergence of OSNs. Our findings highlight the interplay between gene duplication and regulatory evolution in shaping OSN diversity, providing new insights into the evolution and adaptation of olfaction in social insects. This study also sheds light on how genetic innovations contribute to the evolution of complex traits.

Animals↗

Prevalence of olfactory dysfunction: the skövde population-based study.

OBJECTIVES/HYPOTHESIS: Patients with olfactory dysfunction appear repeatedly in ear, nose, and throat practices, but the prevalence of such problems in the general adult population is not known. Therefore, the objectives were to investigate the prevalence of olfactory dysfunction in an adult Swedish population and to relate dysfunction to age, gender, diabetes mellitus, nasal polyps, and smoking habits. STUDY DESIGN: Cross-sectional, population-based epidemiological study. METHODS: A random sample of 1900 adult inhabitants, who were stratified for age and gender, was drawn from the municipal population register of Skövde, Sweden. Subjects were called to clinical visits that included questions about olfaction, diabetes, and smoking habits. Examination was performed with a smell identification test and nasal endoscopy. RESULTS: In all, 1387 volunteers (73% of the sample) were investigated. The overall prevalence of olfactory dysfunction was 19.1%, composed of 13.3% with hyposmia and 5.8% with anosmia. A logistic regression analysis showed a significant relationship between impaired olfaction and aging, male gender, and nasal polyps, but not diabetes or smoking. In an analysis of a group composed entirely of individuals with anosmia, diabetes mellitus and nasal polyps were found to be risk factors, and gender and smoking were not. CONCLUSION: The sample size of the population-based study was adequate, with a good fit to the entire population, which suggests that it was representative for the Swedish population. Prevalence data for various types of olfactory dysfunction could be given with reasonable precision, and suggested risk factors analyzed. The lack of a statistically significant relationship between olfactory dysfunction and smoking may be controversial.

Aged↗

A study on the frequency of olfactory dysfunction.

OBJECTIVES/HYPOTHESIS: Goals of the study were to evaluate the frequency of olfactory dysfunction in a large representative population without sinonasal complaints and to investigate the extent to which general pathological conditions, medications, and aging influence olfaction. STUDY DESIGN: Prospective. METHODS: Results based on an odor identification test ("Sniffin' Sticks") were reported from 1240 subjects. The subjects presented themselves to an otorhinolaryngology outpatient clinic with relatively mild and transitory complaints unrelated to the upper airways. A detailed otorhinolaryngological examination in combination with a standardized interview further ascertained that these patients had no rhinological problems or symptoms relating to sinonasal disease. RESULTS: Apart from the confirmation of the effects of age, gender, and certain otorhinolaryngological diseases on the sense of smell, the study results revealed that certain general diseases (liver diseases, nonotolaryngological cancers) appear to influence olfactory function, whereas other diseases or disorders have little or no impact on olfaction (hypertension, cardiovascular problems). CONCLUSION: The data in the study revealed that olfactory dysfunction among subjects under 65 years of age is more frequent than previously reported.

Adolescent↗

Effect of surgical treatment of olfactory disturbance caused by localized ethmoiditis.

Twenty patients who had disturbance of the sense of smell caused by localized inflammation of the ethmoid sinus were studied to determine the effects of endonasal ethmoidectomy on olfaction. The patients were evaluated pre and post-operatively regarding their subjective olfaction, and with the T&T olfactometry and the Alinamine intravenous administration test, both of which are widely used in Japan. The improvement rate was 70.0% subjectively and 80.0% with T&T olfactometry 6 months after surgery. It is concluded that surgery is worthwhile treatment for olfactory disturbances caused by localized ethmoiditis.

Adult↗

Chemical senses.

In the last decade, studies using approaches from molecular biology have substantially advanced our understanding of the early events in olfaction and taste. The many odorants that we can recognize may well interact with many distinct receptor proteins. Of the four taste qualities that we recognize, studies on salty and sour suggest that these tastes involve ion channels in the membrane of receptor cells while sweets and bitters bind to receptor proteins. Some volatiles (pheromones) play special roles in reproductive behavior via the vomeronasal organ (VNO) and the accessory olfactory system. Initial belief that humans lack a VNO has been questioned recently, thus raising the fascinating possibility of human pheromones. The roles that taste and smell play in the world of the newborn are very different. Acceptance of sweet and rejection of bitter appear to be hard-wired while the affect associated with odors depends much more on experience. Genetic variation may produce total losses (Kallman's syndrome produces anosmia and familial dysautonomia produces ageusia) or losses specific to certain stimuli. The best known of the specific anosmias is that for androstenone, which has no smell to some, a urinous smell to others, and a smell like sandalwood to still others. Analogous to the specific anosmias, some individuals are unable to taste PROP while others, supertasters, perceive PROP to be exceedingly bitter. Clinical studies reveal pathologies responsible for total or partial losses. The olfactory system, dependent on one cranial nerve, is more vulnerable than taste, and total anosmia is a relatively common clinical problem. Three cranial nerves carry taste and two of those nerves inhibit one another such that damage to one disinhibits the other and preserves over-all taste function. Total ageusia is very rare. Throughout these studies we see that taste and olfaction have different properties and often different functions (e.g. odor and reproduction). Yet taste and smell can also be integrated to determine what does or does not enter the body. In Adrian's words, "we are dealing with the sense organs which signal the quality of the air we breathe and that of the food and drink we propose to swallow."

Ageusia↗

Olfactory dysfunction and extent of white matter abnormalities in multiple sclerosis: a clinical and MR study.

BACKGROUND: The relative contribution to the olfactory dysfunction of the lesions in the specific brain regions involved in olfaction compared with the lesions scattered all over the rest of the brain has not been fully clarified yet in patients with multiple sclerosis (MS). The concurrent use of Magnetic Resonance Imaging (MRI) and a standardized test of odor identification ability now permits to study the relation between smell loss and the extent of white matter abnormalities. METHODS: We tested the olfactory function of 40 patients with definite MS and of 40 age-sex- and smoking-habit-matched healthy controls by using the Cross Cultural Smell Identification Test. We measured also the lesion load on T2-weighted images in the inferior-frontal and temporal lobes and in the rest of the brain in MS patients. Therefore, we tried to correlate measures of lesion load and smell test scores. RESULTS: A robust correlation was demonstrated between MR measures of lesion load in the white matter of the olfactory brain region and smell loss (r=-0. 739, P<0.0001). A significant relationship has been found even after taking potential confounding factors, such as sex, age, disease duration, disability, anxiety and depression, into account (r=-0.90, P<0.0001). CONCLUSIONS: Our findings show, in MS patients with stable neurological impairment and no recent disease exacerbation, a correlation between smell loss and the lesion load in the regions of the brain involved in olfaction and support the theory that the extent and severity of MRI abnormalities in specific brain regions are related to the presence of selective neurologic and neuropsychologic impairment.

Adult↗

Acute hyposmia in type 2 diabetes.

During treatment for type 2 diabetes with a diabetic diet (without medication), a 61-year-old Japanese man suddenly developed hyposmia. The fasting plasma glucose was 208 mg/dl and haemoglobin A1c was 8.6%. On investigation, there were no indications of disease of the brain, or the nasal or paranasal sinuses. The intravenous olfaction test yielded no response, indicating suspected neural hyposmia. After 6 months, the symptoms of hyposmia improved without medication, and the intravenous olfaction test results were normal. This clinical course is very similar to that seen with diabetic neuropathy of the third and sixth cranial nerves. We speculate that hyposmia in this case may have been caused by diabetic mononeuropathy of the first cranial nerve.

Blood Glucose↗

Olfactory impairments in patients with unilateral cerebellar lesions are selective to inputs from the contralesional nostril.

Functional imaging studies of olfaction have consistently reported odorant-induced activation of the cerebellum. However, the cerebellar role in olfaction remains unknown. We examined the olfactory and olfactomotor abilities of patients with unilateral cerebellar lesions, comparing performance within subjects across nostrils, as well as between subjects with age-matched and young controls. Regarding olfactory performance, initial testing revealed that patients had a contralesional impairment in olfactory identification but not olfactory detection threshold. However, when tested under conditions that prevented compensatory sniffing strategies, the patients also exhibited a contralesional olfactory detection impairment. Regarding olfactomotor function, a healthy olfactomotor system generates sniffs that are (1) sufficiently vigorous and (2) inversely proportional to odorant concentration in sniff mean airflow velocity, maximum airflow velocity, volume, and duration. Patients' sniffs were lower in overall airflow velocity and volume in comparison with control participants. Furthermore, reduced sniff velocity predicted poorer detection thresholds in patients. Finally, whereas young controls used concentration-dependent sniffs, there was a trend in that direction only for age-matched controls. Patients used sniffs that were concentration invariant. In conclusion, cerebellar lesions impacted olfactory and olfactomotor performance. These findings strongly implicate an olfactocerebellar pathway prominent in odor identification and detection that functionally connects each nostril primarily to the contralateral cerebellum.

Acoustic Stimulation↗