Molecular and Genetic Factors Involved in Olfactory and Gustatory Deficits and Associations with Microbiota in Parkinson's Disease.
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ABSTRACT:
SUBMITTER: Melis M
PROVIDER: S-EPMC8074606 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Vision is a physical sense, whereas olfaction and gustation are chemical senses. Active sensing might function in vision, olfaction, and gustation, whereas passive sensing might function in vision and olfaction but not gustation. To investigate whether each sensory property affected synchrony perception, participants in this study performed simultaneity judgment (SJ) for three cross-modal combinations using visual (red LED light), olfactory (coumarin), and gustatory (NaCl solution) stimuli. We calculated the half-width at half-height (HWHH) and point of subjective simultaneity (PSS) on the basis of temporal distributions of simultaneous response rates in each combination. Although HWHH did not differ significantly among three cross-modal combinations, HWHH exhibited a higher value in cross-modal combinations involving one or two chemical stimuli than in combinations of two physical stimuli, reported in a previous study. The PSS of the olfactory-visual combination was approximately equal to the point of objective simultaneity (POS), whereas the PSS of visual-gustatory, and olfactory-gustatory combinations receded significantly from the POS. In order to generalize these results as specific to chemical senses in regard to synchrony perception, we need to determine whether the same phenomena will be reproduced when performing SJ for various cross-modal combinations using visual, olfactory, and gustatory stimuli other than red LED light, coumarin, and NaCl solution.
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Project description:Background: Olfactory dysfunction often occurs before motor onset in Parkinson's disease (PD) and can be detected with the University of Pennsylvania Smell Identification Test (UPSIT). Based on the Braak hypothesis, the olfactory bulb is one of two sites where disease pathology may start and spread to deeper brain structures. Objective: To evaluate whether a specific pattern of odorant identification on the UPSIT discriminated Parkinson's disease patients with and without freezing of gait. Methods: One hundred and twenty four consecutive participants (33 controls, 31 non-freezers, and 60 freezers) were administered the UPSIT. Using the chi-square test, each odorant on the UPSIT was ranked based on the differential ability of freezers and non-freezers to identify them correctly. Using predictive statistics and confusion matrices, the best combination of odorants and a cut-off score was determined. Results: Freezers had a shift toward a more severe hyposmia classification based on age and sex based normative values. The correct identification of nine odors (bubblegum, chocolate, smoke, wintergreen, paint thinner, orange, strawberry, grass, and peanut) was significantly worse in freezers compared to non-freezers. Correctly identifying ≤ 2 out of 3-odorants (bubblegum, chocolate, and smoke) had a 77% sensitivity and 61% specificity for categorizing freezers. The 3-odorant score was not correlated with disease duration, motor or total UPDRS scores, MoCA scores or age at testing. The predictive statistics were similar when sexes were separately categorized. Conclusions: A 3-odorant score helped categorize freezers and non-freezers with similar sensitivity and specificity to short odorant Parkinson's disease identification batteries.
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Project description:Impaired olfaction is an early pre-motor symptom of Parkinson's disease. The neuropathology underlying olfactory dysfunction in Parkinson's disease is unknown, however ?-synuclein accumulation/aggregation and altered neurogenesis might play a role. We characterized olfactory deficits in a transgenic mouse model of Parkinson's disease expressing human wild-type ?-synuclein under the control of the mouse ?-synuclein promoter. Preliminary clinical observations suggest that rasagiline, a monoamine oxidase-B inhibitor, improves olfaction in Parkinson's disease. We therefore examined whether rasagiline ameliorates olfactory deficits in this Parkinson's disease model and investigated the role of olfactory bulb neurogenesis. ?-Synuclein mice were progressively impaired in their ability to detect odors, to discriminate between odors, and exhibited alterations in short-term olfactory memory. Rasagiline treatment rescued odor detection and odor discrimination abilities. However, rasagiline did not affect short-term olfactory memory. Finally, olfactory changes were not coupled to alterations in olfactory bulb neurogenesis. We conclude that rasagiline reverses select olfactory deficits in a transgenic mouse model of Parkinson's disease. The findings correlate with preliminary clinical observations suggesting that rasagiline ameliorates olfactory deficits in Parkinson's disease.
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Project description:The exact cause of Parkinson's disease (PD), the second most prevalent neurodegenerative disease in modern societies, is still unknown. Many scientists point out that PD is caused by a complex interaction between different factors. Although the main risk factor is age, there are other influences, genetic and environmental, that individually or in combination may trigger neurodegenerative changes leading to PD. Nowadays, research remains focused on better understanding which environmental factors are related to the risk of developing PD and why. In line with the knowledge on evidence on exposures that prevent/delay PD onset or that impact on disease progression, the aims of this review were: (i) to comment on the non-genetic risk factors that mainly affect idiopathic PD; and (ii) to comment on seemingly reliable preventive interventions. We discuss both environmental factors that may affect the central nervous system (CNS) or the intestinal tract, and the likely mechanisms underlying noxious or protective actions. Knowledge on risk, protective factors, and mechanisms may help to envisage why nigral dopaminergic neurons are so vulnerable in PD and, eventually, to design new strategies for PD prevention and/or anti-PD therapy. This article reviews the variety of the known and suspected environmental factors, such as lifestyle, gut microbiota or pesticide exposition, and distinguishes between those that are harmful or beneficial for the PD acquisition or progression. In fact, the review covers one of the most novel players in the whole picture, and we address the role of microbiota on keeping a healthy CNS and/or on preventing the "side-effects" related to aging.
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Project description:The integration of gustatory and olfactory information is essential to the perception of flavor. Human neuroimaging experiments have pointed to the gustatory cortex (GC) as one of the areas involved in mediating flavor perception. Although GC's involvement in encoding the chemical identity and hedonic value of taste stimuli is well studied, it is unknown how single GC neurons process olfactory stimuli emanating from the mouth. In this study, we relied on multielectrode recordings to investigate how single GC neurons respond to intraorally delivered tastants and tasteless odorants dissolved in water and whether/how these two modalities converge in the same neurons. We found that GC neurons could either be unimodal, responding exclusively to taste (taste-only) or odor (odor-only), or bimodal, responding to both gustatory and olfactory stimuli. Odor responses were confirmed to result from retronasal olfaction: monitoring respiration revealed that exhalation preceded odor-evoked activity and reversible inactivation of olfactory receptors in the nasal epithelium significantly reduced responses to intraoral odorants but not to tastants. Analysis of bimodal neurons revealed that they encode palatability significantly better than the unimodal taste-only group. Bimodal neurons exhibited similar responses to palatable tastants and odorants dissolved in water. This result suggested that odorized water could be palatable. This interpretation was further supported with a brief access task, where rats avoided consuming aversive taste stimuli and consumed the palatable tastants and dissolved odorants. These results demonstrate the convergence of the chemosensory components of flavor onto single GC neurons and provide evidence for the integration of flavor with palatability coding. SIGNIFICANCE STATEMENT:Food perception and choice depend upon the concurrent processing of olfactory and gustatory signals from the mouth. The primary gustatory cortex has been proposed to integrate chemosensory stimuli; however, no study has examined the single-unit responses to intraoral odorant presentation. Here we found that neurons in gustatory cortex can respond either exclusively to tastants, exclusively to odorants, or to both (bimodal). Several differences exist between these groups' responses; notably, bimodal neurons code palatability significantly better than unimodal neurons. This group of neurons might represent a substrate for how odorants gain the quality of tastants.
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Project description:PURPOSE:At the time of writing, there is a pandemic affecting virtually every country on Earth. There is considerable discussion amongst clinicians as well as lay people about anosmia and ageusia in COVID-19 sufferers. We aimed to report the results from comprehensive olfactory and gustatory testing in a series of hospital in-patients. METHODS:The prospective study evaluated 81 individuals with a COVID-19 infection, as confirmed by 2019 n-cov Real-Time PCR laboratory testing. The control group consisted of forty individuals with COVID-19 negative. Olfactory and gustatory testings were carried out by an examiner utilizing stringent safety standards and wearing full personal protective equipment. The results obtained in the case group were then compared with those obtained for the controls. RESULTS:In the case group, 41(50.6%) of patients were male and 40 (49.4%) were female, mean age of 54.16?±?16.98 years (18-95). In the control group, 21 (52.5%) of subjects were male and 19 (47.5%) were female, and mean age was 55?±?15.39 years (18-90). Fifty (61.7%) COVID-19-positive patients had complaints related to olfaction. The distribution of olfactory symptoms in the case group differed at the level of statistical significance from the control group (p?<?0.001). Turning to gustatory abnormalities, within the case group, 22 individuals (27.2%) had taste malfunction. A statistically significant difference was found in the distribution of gustatory abnormalities between cases and controls (p?<?0.001). CONCLUSIONS:Olfactory and gustatory dysfunctions are strongly associated with SARS-CoV-2 infection. Hyposmia with or without hypogeusia is potentially a reliable indicator of latent COVID-19.
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Project description:It is easier to detect mixtures of gustatory and olfactory flavorants than to detect either component alone. But does the detection of mixtures exceed the level predicted by probability summation, assuming independent detection of each component? To answer this question, we measured simple response times (RTs) to detect brief pulses of one of 3 flavorants (sucrose [gustatory], citral [olfactory], sucrose-citral mixture) or water, presented into the mouth by a computer-operated, automated flow system. Subjects were instructed to press a button as soon as they detected any of the 3 nonwater stimuli. Responses to the mixtures were faster (RTs smaller) than predicted by a model of probability summation of independently detected signals, suggesting positive coactivation (integration) of gustation and retronasal olfaction in flavor perception. Evidence for integration appeared mainly in the fastest 60% of the responses, indicating that integration arises relatively early in flavor processing. Results were similar when the 3 possible flavorants, and water, were interleaved within the same session (experimental condition), and when each flavorant was interleaved with water only (control conditions). This outcome suggests that subjects did not attend selectively to one flavor component or the other in the experimental condition and further supports the conclusion that (late) decisional or attentional strategies do not exert a large influence on the gustatory-olfactory flavor integration.
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Project description:The intestinal microbiota influence neurodevelopment, modulate behavior, and contribute to neurological disorders. However, a functional link between gut bacteria and neurodegenerative diseases remains unexplored. Synucleinopathies are characterized by aggregation of the protein ?-synuclein (?Syn), often resulting in motor dysfunction as exemplified by Parkinson's disease (PD). Using mice that overexpress ?Syn, we report herein that gut microbiota are required for motor deficits, microglia activation, and ?Syn pathology. Antibiotic treatment ameliorates, while microbial re-colonization promotes, pathophysiology in adult animals, suggesting that postnatal signaling between the gut and the brain modulates disease. Indeed, oral administration of specific microbial metabolites to germ-free mice promotes neuroinflammation and motor symptoms. Remarkably, colonization of ?Syn-overexpressing mice with microbiota from PD-affected patients enhances physical impairments compared to microbiota transplants from healthy human donors. These findings reveal that gut bacteria regulate movement disorders in mice and suggest that alterations in the human microbiome represent a risk factor for PD.
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Project description:BackgroundThe novel Coronavirus Disease-19 (COVID-19) continues to have profound effect on global health. Our aim was to evaluate the prevalence and characterize specific symptoms associated with COVID-19.MethodsThis retrospective study included 326 patients with confirmed SARS-CoV-2 infection evaluated at the Emergency Department of the Umberto I Polyclinic Hospital, Rome, Italy between March 6th and April 30th, 2020. In order to assess xerostomia, olfactory and gustatory dysfunctions secondary to COVID-19, a telephone-based a modified survey obtained from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 for taste and smell disorders and the Fox Questionnaire for dry mouth were administered to 111 patients (34%) after discharge between June 4th and June 12th.ResultsTaste dysfunction was the most common reported symptom (59.5%; n = 66), followed by xerostomia (45.9%; n = 51) and olfactory dysfunctions (41.4%; n = 46). The most severe symptom was olfactory dysfunction with a median severity score of 8.5 (range: 5-10). Overall 74.5% (n = 38) of patients with xerostomia, 78.8% (n = 52) of patients with gustatory dysfunctions and 71.1% (n = 33) of patients with olfactory dysfunctions reported that all symptoms appeared before COVID-19 diagnosis. Overall, the majority of patients reported one symptom only (45.9%, n = 51), 37 (33.3%) reported the association of two symptoms, and 23 (20.7%) patients reported the association of three symptoms at the same time.ConclusionXerostomia, gustatory and olfactory dysfunctions may present as a prodromal or as the sole manifestation of COVID-19. Awareness is fundamental to identify COVID-19 patients at an early stage of the disease and limit the spread of the virus.
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Project description:Animals such as bumblebees use chemosensory cues to both locate and evaluate essential resources. Increasingly, it is recognized that microbes can alter the quality of foraged resources and produce metabolites that may act as foraging cues. The distinct nature of these chemosensory cues however and their use in animal foraging remain poorly understood. Here, we test the hypothesis that species of nectar-inhabiting microbes differentially influence pollinator attraction and feeding via microbial metabolites produced in nectar. We first examined the electrophysiological potential for bumblebee (Bombus impatiens) antennal olfactory neurons to respond to microbial volatile organic compounds (mVOCs), followed by an olfactory preference test. We also assessed gustatory preferences for microbial-altered nectar through both no-choice and choice feeding assays. Antennal olfactory neurons responded to some mVOCs, and bees preferred nectar solutions inoculated with the bacterium Asaia astilbes over the yeast Metschnikowia reukaufii based on volatiles alone. However, B. impatiens foragers consumed significantly more Metschnikowia-inoculated nectar, suggesting distinct roles for mVOCs and non-volatile metabolites in mediating both attraction and feeding decisions. Collectively, our results suggest that microbial metabolites have significant potential to shape interspecific, plant-pollinator signalling, with consequences for forager learning, economics and floral host reproduction.
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