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#213
Life Satisfaction In Cancer Patients With And Without Chemosensory Dysfunction
Victoria Esparza1, Vicente Ramirez1, Alissa Nolden2, Kara Stromberg 3, Valentina Parma 1
1Monell Chemical Senses Center, Philadelphia , PA, United States
2University of Massachusetts Amherst , Amherst , MA, United States
3Fox Chase Cancer Center , Philadelphia , PA, United States
Chemosensory dysfunctions (CD) are symptoms often experienced by cancer patients. Albeit common, these symptoms lack guidelines for management and are rarely addressed by healthcare providers, and therefore, how taste and smell dysfunctions affect quality of life in cancer patients is understudied. To address this gap, we analyzed data from the 2021 National Health Interview Survey (NHIS). The sample included 3,654 subjects (mean±SD: 68±13 years, range:18-99 years; 58% F; 85% non-hispanic white) who self-reported having cancer and self-assessed whether they had difficulty tasting, difficulty smelling, and reported life satisfaction (binary) in the last 12 months. 20.3% reported smell dysfunction (n=741; 70±12 years; 49% F) and 11.9% reported taste dysfunction (n=435; 70±12 years; 52% F), and 9% reported both smell and taste dysfunction (n=330; 71±12 years; 51% F). After adjusting for age and sex, a logistic regression revealed that cancer patients reporting difficulty tasting had 64% decreased odds of reporting life satisfaction compared to those who did not report difficulty tasting (z=-6.3, p<0.0001, CI[.27,.50]). Similarly, cancer patients reporting difficulty smelling had 43% decreased odds of reporting life satisfaction compared to those who did not report trouble smelling (z=-3.7, p<0.0001, CI[.43,.77]). Considering that the prevalence of CD is often underestimated when measured with self-reports, we consider this a conservative scenario to test the hypothesis that CD is associated with decreased life satisfaction in cancer. These findings call for a serious assessment of CD in cancer patients to improve quality of life.
#214
Reports of Smell and Taste Adverse Events from GLP-1 RA’s
Ryann Kolb1, Emmanuel Nartey2, Alicia Lozano2, Alexandra Hanlon2, Vicente Ramirez1, Valentina Parma1
1Monell Chemical Senses Center, Philadelphia, PA, United States
2Center for Biostatistics and Health Data Science, Virginia Tech, Roanoke, VA, United States
Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed for treating type 2 diabetes and obesity by regulating appetite, a function heavily influenced by taste and smell. Post-marketing surveillance data from the FDA Adverse Event (AE) Reporting System was used to evaluate the effects of GLP-1 RAs on taste and smell. Methods: We analyzed AE reports (01/01/2019–09/30/2024) on taste disorders (dysgeusia, ageusia, hypogeusia, non-specified taste disorder) and smell disorders (anosmia, hyposmia, parosmia, phantosmia) for GLP-1 RAs (semaglutide, dulaglutide, exenatide, liraglutide, lixisenatide; N=113,452) and non-GLP-1 RA drugs with known chemosensory adverse effects [i.e., metformin (non-GLP-1 RA drug for diabetes), nirmatrelvir (Paxlovid), and terbinafine (antifungal); N=257,356] using a standard disproportionality approach. Results: As expected, non-GLP-1 RA drugs exhibited high (>2.0) Reporting Odds Ratios (ROR) for one or more chemosensory AEs, with the largest effects for taste dysfunction. Examples include metformin for parosmia (ROR=4.8; 95% CI 3.8-6.0), nirmatrelvir for dysgeusia (ROR=83.0; 95% CI 80.3-85.7), and terbinafine for ageusia (ROR=39.0; 95% CI 32.8-46.3). Although GLP-1 RAs overall demonstrated high associations among non-specified taste disorders (ROR=2.1; 95% CI 1.9-2.3) and parosmia (ROR=2.5; 95% CI 2.0-3.1), these effects are lower than observed for the non-GLP-1 RA drugs. Among GLP-1 RAs, semaglutide demonstrates the strongest associations, with an ROR=3.6 [95% CI 3.2-4.1] for taste disorder and ROR=4.4 [95% CI 3.3-5.8] for parosmia. Conclusion: GLP-1 RAs show significant associations with taste and smell disorders, the nature of which requires further study.
#111
Umami taste detection in children versus adults
Claudia M. Asensio1, Jessica G. Nicanor Carreon 1, Julie A. Mennella2, M. Yanina Pepino1
1University of Illinois Urbana-Champaign, Urbana, IL, United States
2Monell Chemical Senses Center, Philadelphia, PA, United States
Adults and children live in different sensory worlds. While children are less sensitive to detecting sweetness and more sensitive to detecting bitterness than adults, there is surprisingly little research using the same methods to compare their sensitivities for other tastes—particularly for umami. Here, we conducted a secondary analysis of data from children (8-14 years; n=85) and adults (21-67 years; n=71) to determine whether there are age-related changes in taste sensitivity for monosodium glutamate (MSG). Using identical procedures for both groups, MSG detection thresholds were determined via a two-alternative, forced-choice paired comparison tracking procedure previously validated for use in children. Because obesity is associated with reduced MSG sensitivity in adults, we also examined MSG thresholds as a function of body adiposity. Body fat percentage was estimated using bioimpedance electrical analysis in the majority (75%) of participants and dual-energy X-ray absorptiometry in a subset of adults. We found that, like sweet taste, children were less sensitive to detecting MSG than adults (log means of -2.74±0.04 vs. -2.86±0.04 in children vs. adults, respectively; ~2.4mM vs. 1.9mM MSG P<.05). Additionally, we observed a trend for age group to interact with adiposity (P=0.08). Adults with excess adiposity were less sensitive to MSG than those without excess adiposity (-2.79±0.06 vs. -3.03±0.10; ~2.3mM vs. 1.3mM MSG P<.05). However, no such differences were observed among children. While the mechanisms behind children’s reduced sensitivity to detect the nutritive tastes of umami and sweet—and the lack of an association with adiposity— remain unknown, we hypothesize that higher metabolic demands for growth during development interact with the taste system. Future studies are needed.
#160
Olfactory Bulb Activity And Active Sniffing During Naturalistic Foraging In Freely Moving Mice
Jesse A. Smith1, Kevin Bolding2, Jiayue Tai3, Ian Davison1
1Boston University, Boston, MA, United States
2Monell Chemical Senses center, Philadelphia, PA, United States
3Tufts University, Medford, MA, United States
Understanding the critical role of the olfactory system in guiding naturalistic foraging behaviors promises to provide fundamental insights into sensory perception and ecological adaptations. Mice rely heavily on their olfactory senses to navigate complex environments and locate potential food sources. Although odor-evoked activity has been intensively studied in head-fixed animals, little is known about the dynamic sensory signals acquired by freely moving animals when actively sampling their environment. To address the gap in knowledge about real-time olfactory sensory-motor strategies, we engineered a novel large-area miniscope allowing us to image glomerular activity across both hemispheres of the main olfactory bulb (MOB). MOB imaging in freely moving animals revealed that sensory information was largely confined to distances within 10 cm of the odor source. Average glomerular activation increased with proximity to odor sources, allowing us to map well-studied concentration-dependent coding onto spatial measures. Interestingly, glomerular activity often showed directional tuning near the odor source, and these signals predicted future turning behavior. We used implanted thermistors to directly relate sniffing activity to behavior and neural activity, revealing that animals only obtain sensory information on a relatively sparse subset of sniff samples. Integrating sniff and imaging measurements should help reveal how active sampling strategies inform moment-to-moment navigational decisions during odor source localization.
#193
Chronic olfactory inflammation: its impact on the olfactory epithelium, olfactory bulb and brain cognitive function
Derek Cox, Morning Dove Rose, Kaitlyn Taylor-Cox, Diego Rodriguez-Gil, Russell Brown, Cuihong Jia
Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University , Johnson City, TN, United States
Olfactory deficits positively correlate to cognitive dysfunction and are proposed as an early predictor for neurodegenerative diseases. Chronic olfactory inflammation following viral nose infection, including COVID-19, leads to loss of the sense of smell. Whether chronic olfactory inflammation impairs brain function, such as COVID-related cognition and memory decline, is not fully understood. Using an inducible olfactory inflammation (IOI) mouse model that induces TNFα expression under Cyp2g1, a marker for the olfactory epithelium (OE), we investigated the effect of chronic olfactory inflammation on OE, olfactory bulb (OB) and brain cognitive function. Six weeks after induction of TNFα, a massive inflammatory response was observed in the OE, including upregulation of IL-1β, IFNγ, IL-6, and CCL2. Olfactory sensory neurons were lost in a patchy pattern that matches the differential expression of Cyp2g1 in the OE. Basal stem cell proliferation was absent in injured and intact regions. Smell function, measured by buried food and olfactory habituation/dishabituation tests, was also impaired. In the OB, IOI elevated IL-1β and IL-6 mRNA, activated microglia and enhanced leukocyte infiltration. These data indicate that chronic OE inflammation disrupts the OE and its regenerative capacity, which then causes an inflammatory pathology in the OB. Importantly, hippocampus-mediated learning and memory, tested by Barnes maze and novel object recognition, was also compromised in the IOI mice. The IOI-induced hippocampal pathology is under investigation. Together, this study reveals an OE-OB-hippocampal pathway that might be correlated to cognitive decline following COVID-19-induced chronic olfactory inflammation.
#3
Characterizing olfactory brain responses in young infants
Laura Shanahan1, Leena Mithal2, Marci Messina3, Emma Office2, Lauren Wakschlag2, Patrick Seed2, Thorsten Kahnt4
1Rhodes College, Memphis, TN, United States
2Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
3Northwestern Memorial Hospital, Chicago, IL, United States
4National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, United States
Odor perception plays a critical role in early human development, but the underlying neural mechanisms are not fully understood. To investigate these, we presented two appetitive and two aversive odors to infants at one month of age while recording functional magnetic resonance imaging (fMRI) and nasal airflow data. To enable MRI scanning at this early age, infants slept during odor presentation. Whole brain analyses revealed that compared to clean air, odors evoke fMRI activity in bilateral olfactory cortex (encompassing piriform cortex and amygdala) as well as thalamus. Analysis of odor-evoked fMRI responses in anatomically defined regions of interest further showed significant responses in piriform cortex, amygdala, olfactory tubercle, and entorhinal cortex, whereas no significant responses were found in anterior olfactory nucleus. Moreover, fMRI response magnitudes in piriform cortex and amygdala differed across odors. However, in contrast with prior work in adults, we did not find evidence that odor stimuli evoke discriminable fMRI activity patterns using two different multivariate pattern analysis techniques. Finally, the average inhale airflow rate was higher for appetitive odors than aversive odors, suggesting that, similar to adults, infants may modulate their respiration to reflect odor valence. Overall, these results show strong neural responses to odors at this early developmental stage and highlight nasal airflow as a behavioral metric for assessing odor preferences in infants.
#108
GLP-1 Receptor Agonists Significantly Impair Taste Function
Richard Doty & Rafa Khan
University of Pennsylvania, Philadelphia, PA, United States
Over 10% of the US population are prescribed glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to combat obesity. Although they decrease cravings for foods, their influence on chemosensory function is unknown. We employed state-of-the-art quantitative taste and smell tests to address this issue. The 53-item Waterless Empirical Taste Test (WETT®) and the 40-item University of Pennsylvania Smell Identification Test (UPSIT®) were completed by 46 persons taking GLP-1 RAs and 46 controls matched on age, sex, smoking behavior, and COVID-19 infection histories. Data were analysed using analyses of variance. The WETT® scores were significantly diminished in the GLP-1 RA group relative to controls [total means (95% CIs)=28.61 (25.66,31.56) and 40.63 (38.35,42.91), p<0.001, η2=0.37]. Eighty five percent of the GLP-1 subjects scored worse than their individually matched controls. All 5 WETT® subtest scores were similarly affected (ps<0.001). Smell function, although slightly decreased on average, was not significantly impacted (p=0.076). Women outperformed men on all tests. Remarkably, UPSIT® and WETT® scores were higher, i.e., better, in those reporting nausea, diarrhoea, and other GLP-1-related side effects. This study demonstrates, for the first time, that GLP-1 RAs alter the function of a major sensory system, significantly depressing the perception of all five basic taste qualities. The physiologic basis of this effect is unknown but may involve GLP-1 receptors in the brainstem and afferent taste pathways, as well as vagus nerve-related processes.
#55
Premotor inputs modulate preparatory activity in the gustatory cortex
John Chen1,2 & Alfredo Fontanini1,2
1Program in Neuroscience, Stony Brook, NY, United States
2Department of Neurobiology and Behavior, Stony Brook, NY, United States
Studies have demonstrated multiple roles for the gustatory cortex (GC) in processing cognitive signals related to a gustatory experience. Importantly, GC represents the progression of taste sensory coding into preparatory signals predicting lick decisions in the context of a delayed-response task where taste guides directional licking. While decision-related activity was observed in GC, the neural mechanisms underlying this representation have not been studied. Given the connections between GC and frontal cortices involved in guiding goal-directed actions, external inputs may modulate preparatory activity in GC during the motor planning of lick decisions. A probable candidate in coordinating GC activity in the context of a delayed-response task is the anterior-lateral motor cortex (ALM). This subregion of the mouse frontal cortex is involved in the planning and execution of goal-directed licking. In this study, we investigated the coordination between GC and ALM in a taste-based, directional licking task with a delay period. Simultaneous electrophysiological recordings were performed to compare the temporal coding of task variables between the two regions. Preparatory activity for licking was found to begin earlier in ALM than in GC. Analysis of trial-type selectivity revealed distinct representations in decision-related coding between the two regions. To determine if ALM is a source of preparatory signals to GC, we performed transient optogenetic inhibition of ALM during the delay period while recording GC activity. Inactivation of ALM reduced direction selective preparatory activity in GC, supporting a role for ALM as a source of such signals to GC. Our findings demonstrate that cortical premotor inputs significantly contribute to GC activity during taste-guided decision making.
#144
Deficits in Olfactory Behaviors in Mice After Subchronic E-Cigarette Exposure
Sean O'Sullivan1, Janae Gordon1, Saheedat Odetayo1, Kafui Ameko1, Mufaro Chiduza1, Agnes Koodaly1, Ashkon Hazrati1, Michael Ack1, Virginia Murray1, Leyla Aydin1,2, Tatsuya Ogura1, Weihong Lin1
1University of Maryland, Baltimore County, Baltimore, MD, United States
2University of Maryland, College Park, College Park, MD, United States
Electronic cigarettes (e-cigarettes) are used daily by millions of people worldwide. However, e-cigarette vapor contains various volatile organic compounds, such as formaldehyde, and heavy metals. Previously published studies established a relationship between environmental exposure to these toxicants and olfactory dysfunction. However, the synergistic effects of vaping these compounds and olfactory-guided behavioral impairment has not been investigated. This project aims to investigate the effect of e-cigarette vapor components on the olfactory system. A cohort of mice were split into three treatment groups and one control group: propylene glycol/vegetable glycerin (PG/VG) only, PG/VG + flavorants, PG/VG + flavorants + heavy metals, and air exposure. Groups were exposed twice daily for 8 weeks to simulate subchronic e-cigarette use. Olfactory-guided behavioral assays were performed before and after the exposure to determine potential behavioral effects. We employed a buried food test and a urine/water preference T-Maze to explore if vaping disrupts foraging and odor-guided discrimination. Videos from each group were recorded and analyzed using tracking software from Bonsai. Our findings show that e-cigarette exposure increases the latency to discover buried food, with worse performance in our PG/VG + flavorants and the PG/VG + flavorants + heavy metals groups. We observed lowered preference for a known attractive odor (urine of the opposite sex) in the PG/VG + flavorant + heavy metals group as indicated by decreased time spent with urine compared to the water control. The results suggest that repeated exposure to the flavorants and heavy metals found in e-cigarette vapors may lead to impaired olfactory detection and discrimination, and may precede further vaping induced olfactory dysfunction.
