Olfactory Areas Research Articles

Measuring olfactory‐related brain region volume loss in MCI and AD using structural MRI

AbstractBackgroundAlzheimer disease (AD) is a chronic disorder that affects millions of individuals worldwide. Olfactory dysfunction is a common symptom of several neurological disorders including AD. Olfactory dysfunction can be an early alteration heralding the presence of AD. Studying the pattern of alterations in olfaction‐related brain regions might help detection of neurodegenerative diseases at an earlier stage. Objectives of this study are to assess the volume of olfactory areas associated with odour processing in healthy elderly, MCI and AD populations using structural MRI scans. To test whether there are any differences in the volume of olfactory related regions between patients and healthy controls. To determine whether there is an effect of sex on olfactory‐related brain regions’ volume loss.MethodNeurologically healthy participants aged 66‐85 (n = 95), MCI aged 58‐86 (n = 81) and mild probable AD aged 55‐88 (n = 37) participants were recruited. T1‐ weighted MRI scans acquired at 1.5T were processed using SPM12. Smoothed images were used to extract the volume of olfactory cortex, hippocampus, parahippocampus, amygdala, orbitofrontal cortex and entorhinal cortex.ResultOne‐way ANOVA analyses showed a significant reduction in all olfaction‐related brain regions (p≤0.0001). Post‐hoc multiple comparison tests showed a significant reduction in volume in the AD group in all olfaction‐related brain regions. In the MCI group, a significantly smaller volume than the healthy controls was found in four of the selected olfactory‐related brain regions (namely, hippocampus, parahippocampus, amygdala and entorhinal cortex) for the total and left volume in the female group only. Additionally in the female MCI, the volume of the right entorhinal cortex however, was also significantly smaller than that of the control group. When adjusting for MMSE, however, between group differences in all olfaction‐related brain regions were no longer significant.ConclusionThese preliminary data show a significant reduction in grey matter volume in all olfaction‐related brain regions. Grey matter volume loss in these regions appears to be a good proxy of disease severity.

Olfactory Loss and Brain Connectivity after COVID-19: Structural Follow-Up at One Year.

The structural connectivity from the primary olfactory cortex to the main secondary olfactory areas was previously reported as relatively increased in the medial orbitofrontal cortex in a cohort of 27 recently SARS-CoV-2-infected (COV+) subjects, of which 23/27 had clinically confirmed olfactory loss, compared to 18 control (COV-) normosmic subjects, who were not previously infected. To complement this finding, here we report the outcome of an identical high angular resolution diffusion MRI analysis on follow-up data sets collected in 18/27 COV+ subjects (10 males, mean age ± SD: 38.7 ± 8.1 years) and 10/18 COV- subjects (5 males, mean age ± SD: 33.1 ± 3.6 years) from the previous samples who repeated both the olfactory functional assessment and the MRI examination after ~1 year. By comparing the newly derived subgroups, we observed that the increase in the structural connectivity index of the medial orbitofrontal cortex was not significant at follow-up, despite 10/18 COV+ subjects were still found hyposmic after ~1 year from SARS-CoV-2 infection. We concluded that the relative hyperconnectivity of the olfactory cortex to the medial orbitofrontal cortex could be, at least in some cases, an acute or reversible phenomenon linked to the recent SARS-CoV-2 infection with associated olfactory loss.

Diffusion-weighted imaging measurements of central smell regions in COVID-19 patients: insular gyrus, corpus amygdala, and thalamus.

The aim of this study was to investigate central smell centers with cranial magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) in COVID-19. This retrospective study evaluated cranial MRI images of 54 adults. The experimental group (Group 1), consisting of 27 patients with positive COVID-19 real-time polymerase chain reaction (RT-PCR) assays, was compared to the control group (Group 2), comprising 27 healthy controls without COVID-19. The apparent diffusion coefficient (ADC) values were measured in the corpus amygdala, thalamus, and insular gyrus in both groups. Thalamus ADC values of the COVID-19 group were significantly lower compared to the control group bilaterally. However, no differences were found in the insular gyrus and corpus amygdala ADC values between the two groups. Positive correlations were observed between the insular gyrus and corpus amygdala ADC values and the thalamus ADC values. Insular gyrus ADC values (right) were higher in females. Left insular gyrus and corpus amygdala ADC values were higher in COVID-19 patients with smell loss. Right insular gyrus and left corpus amygdala ADC values were lower in COVID-19 patients with lymphopenia. Diffusion restriction in olfactory areas can be considered an obvious indicator that the COVID-19 virus affects and damages the immune system at the neuronal level. Given the urgency and lethality of the current pandemic, acute onset odor loss should be considered a high suspicion-adhesive index for patients with SARS-CoV-2 infection. Therefore, the sense of smell should be considered and evaluated simultaneously with other neurological symptoms. DWI should be widely used as an early imaging method for central nervous system (CNS) infections, especially in relation to COVID-19.

Aberrant olfactory network functional connectivity in people with olfactory dysfunction following COVID-19 infection: an exploratory, observational study

Olfactory impairments and anosmia from COVID-19 infection typically resolve within 2-4 weeks, although in some cases, symptoms persist longer. COVID-19-related anosmia is associated with olfactory bulb atrophy, however, the impact on cortical structures is relatively unknown, particularly in those with long-term symptoms. In this exploratory, observational study, we studied individuals who experienced COVID-19-related anosmia, with or without recovered sense of smell, and compared against individuals with no prior COVID-19 infection (confirmed by antibody testing, all vaccine naïve). MRI Imaging was carried out between the 15th July and 17th November 2020at the Queen Square House Clinical Scanning Facility, UCL, United Kingdom. Using functional magnetic resonance imaging (fMRI) and structural imaging, we assessed differences in functional connectivity (FC) between olfactory regions, whole brain grey matter (GM) cerebral blood flow (CBF) and GM density. Individuals with anosmia showed increased FC between the left orbitofrontal cortex (OFC), visual association cortex and cerebellum and FC reductions between the right OFC and dorsal anterior cingulate cortex compared to those with no prior COVID-19 infection (p<0.05, from whole brain statistical parametric map analysis). Individuals with anosmia also showed greater CBF in the left insula, hippocampus and ventral posterior cingulate when compared to those with resolved anosmia (p<0.05, from whole brain statistical parametric map analysis). This work describes, for the first time to our knowledge, functional differences within olfactory areas and regions involved in sensory processing and cognitive functioning. This work identifies key areas for further research and potential target sites for therapeutic strategies. This study was funded by the National Institute for Health and Care Research and supported by the Queen Square Scanner business case.

Age-Related In Vivo Structural Changes in the Male Mouse Olfactory Bulb and Their Correlation with Olfactory-Driven Behavior

Olfactory areas in mammalian brains are linked to centers that modulate behavior. During aging, sensitivity to odors decreases and structural changes are described in olfactory areas. We explored, in two groups of male mice (young and elderly, 6 and 19 months old, respectively), the link between the changes in olfactory bulb structure, detected with magnetic resonance imaging, and behavioral changes in a battery of tests on motor, olfactory, cognitive performance, and emotional reactivity. The behavioral pattern of elderly mice appears less anxious, being less scared by new situations. Additionally, the olfactory bulb of young and elderly mice differed in two variables derived from magnetic resonance imaging (fractional anisotropy and T2 maps). A random forest approach allowed to select the variables most predictive of the differences between young and elderly mice, and correlations were found between three behavioral variables indicative of anxious behavior and the two magnetic resonance variables mentioned above. These data suggest that in the living mouse, it is possible to describe co-occurring age-related behavioral and structural changes in the olfactory bulb. These data serve as a basis for studies on normal and pathological aging in the mouse, but also open new opportunities for in vivo human aging studies.

Organizational Principles of the Centrifugal Projections to the Olfactory Bulb.

Centrifugal projections in the olfactory system are critical to both olfactory processing and behavior. The olfactory bulb (OB), the first relay station in odor processing, receives a substantial number of centrifugal inputs from the central brain regions. However, the anatomical organization of these centrifugal connections has not been fully elucidated, especially for the excitatory projection neurons of the OB, the mitral/tufted cells (M/TCs). Using rabies virus-mediated retrograde monosynaptic tracing in Thy1-Cre mice, we identified that the three most prominent inputs of the M/TCs came from the anterior olfactory nucleus (AON), the piriform cortex (PC), and the basal forebrain (BF), similar to the granule cells (GCs), the most abundant population of inhibitory interneurons in the OB. However, M/TCs received proportionally less input from the primary olfactory cortical areas, including the AON and PC, but more input from the BF and contralateral brain regions than GCs. Unlike organizationally distinct inputs from the primary olfactory cortical areas to these two types of OB neurons, inputs from the BF were organized similarly. Furthermore, individual BF cholinergic neurons innervated multiple layers of the OB, forming synapses on both M/TCs and GCs. Taken together, our results indicate that the centrifugal projections to different types of OB neurons may provide complementary and coordinated strategies in olfactory processing and behavior.

Technique of flat-mount immunostaining for mapping the olfactory epithelium and counting the olfactory sensory neurons.

The pathophysiology underlying olfactory dysfunction is still poorly understood, and more efficient biomolecular tools are necessary to explore this aspect. Immunohistochemistry (IHC) on cross sections is one of the major tools to study the olfactory epithelium (OE), but does not allow reliable counting of olfactory sensory neurons (OSNs) or cartography of the OE. In this study, we want to present an easy immunostaining technique to compensate for these defects of IHC. Using the rat model, we first validated and pre-screened the key OSN markers by IHC on cross sections of the OE. Tuj-1, OMP, DCX, PGP9.5, and N-cadherin were selected for immunostaining on flat-mounted OE because of their staining of OSN dendrites. A simple technique for immunostaining on flat-mounted septal OE was developed: fixation of the isolated septum mucosa in 0.5% paraformaldehyde (PFA) preceded by pretreatment of the rat head in 1% PFA for 1 hour. This technique allowed us to correctly reveal the olfactory areas using all the 5 selected markers on septum mucosa. By combining the mature OSN marker (OMP) and an immature OSN marker (Tuj-1), we quantified the mature (OMP+, Tuj-1-), immature (OMP-, Tuj-1+), transitory (OMP+, Tuj-1+) and total OSN density on septal OE. They were respectively 42080 ± 11820, 49384 ± 7134, 14448 ± 5865 and 105912 ± 13899 cells per mm2 (mean ± SD). Finally, the same immunostaining technique described above was performed with Tuj-1 for OE cartography on ethmoid turbinates without flat-mount.

Ablation of AQP5 gene in mice leads to olfactory dysfunction caused by hyposecretion of Bowman's gland.

Smell detection depends on nasal airflow, which can make absorption of odors to the olfactory epithelium by diffusion through the mucus layer. The odors then act on the chemo-sensitive epithelium of olfactory sensory neurons (OSNs). Therefore, any pathological changes in the olfactory area, for instance, dry nose caused by Sjögren's Syndrome (SS) may interfere with olfactory function. SS is an autoimmune disease in which aquaporin (AQP) 5 autoantibodies have been detected in the serum. However, the expression of AQP5 in olfactory mucosa and its function in olfaction is still unknown. Based on the study of the expression characteristics of AQP5 protein in the nasal mucosa, the olfaction dysfunction in AQP5 knockout (KO) mice was found by olfactory behavior analysis, which was accompanied by reduced secretion volume of Bowman's gland by using in vitro secretion measure system, and the change of acid mucin in nasal mucus layer was identified. By excluding the possibility that olfactory disturbance was caused by changes in OSNs, the result indicated that AQP5 contributes to olfactory functions by regulating the volume and composition of OE mucus layer, which is the medium for the dissolution of odor molecules. Our results indicate that AQP5 can affect the olfactory functions by regulating the water supply of BGs and the mucus layer upper the OE that can explain the olfactory loss in the patients of SS, and AQP5 KO mice might be used as an ideal model to study the olfactory dysfunction.

Correlation analysis of flow parameters in the olfactory cleft and olfactory function

The olfaction is related to flow in the olfactory cleft. However, There is a lack of studies on the relationship between flow characteristics of the olfactory cleft and olfactory function. In this study, the anatomical structure of the olfactory cleft was reconstructed in three dimensions using the raw data obtained from the CT scans of sinuses of 32 enrolled volunteers. The Sniffin’ Sticks test was used to examine the olfaction. We investigated the correlation between airflow parameters and olfactory function of the olfactory cleft in healthy adults by the computational fluid dynamics method. We found that three parameters, airflow, airflow velocity, and airflow ratio, were highly positively correlated with olfactory function. The mean pressure was not correlated with the olfactory function. Furthermore, there is the strongest correlation between air flow through the olfactory cleft and olfactory function. The correlation between the mean velocity in the anterior olfactory cleft region and olfaction was relatively poor, while the airflow velocity at the posterior olfactory cleft region was enhanced gradually. The correlation between the airflow ratio and olfaction was optimal in the initial position of superior turbinate. The flow parameters in the posterior olfactory cleft area were more stable.

Effects of COVID-19 on the Human Central Olfactory System: A Natural Pre-Post Experiment.

Reduced olfactory function is the symptom with the highest prevalence in coronavirus disease 2019 (COVID-19) with nearly 70% of infected individuals experiencing partial or total loss of their sense of smell at some point during the disease. The exact cause is not known, but beyond peripheral damage, studies have demonstrated insults to both the olfactory bulb and central olfactory brain areas. However, these studies often lack both baseline pre-COVID-19 assessments and control groups, and the effects could, therefore, simply reflect pre-existing risk factors. Shortly before the COVID-19 outbreak, we completed an olfactory-focused study, which included structural MR brain images and a full clinical olfactory test. Opportunistically, we invited participants back 1 year later, including 9 participants who had experienced mild-to-moderate COVID-19 (C19+) and 12 who had not (C19-), creating a natural pre-post experiment with a control group. Despite C19+ participants reporting subjective olfactory dysfunction, few showed signs of objectively altered function. Critically, all except 1 individual in the C19+ group had reduced olfactory bulb volume (average reduction, 14.3%), but this did not amount to a significant statistical difference compared with the control group (2.3%) using inference statistics. We found no morphologic differences in olfactory brain areas but stronger functional connectivity between olfactory brain areas in the C19+ group at the postmeasure. Our data suggest that COVID-19 might cause long-term reduction in olfactory bulb volume and altered functional connectivity but with no discernible morphologic differences in cerebral olfactory regions.

RETRACTED: Health risks and respiratory intake of submicron particles in the working environment: A case study

Background: Powder-coating processes have been extensively used in various industries. The submicron particles generated during the powder-coating process in the workplace have complex compositions and can cause serious diseases. The purpose of this study was to better understand the health risks and respiratory intake of submicron particles during the powder coating process.Methods: The concentrations of and variations in submicron particles were measured using real-time instruments. The health risks of submicron particles were analyzed using the Stoffenmanager Nano model. A new computational fluid dynamics model was used to assess the respiratory intake of ultrafine particles (UFPs), which was indicated by the deposited dosage of UFPs in the olfactory area, nasal cavity, and lungs. The deposited doses of UFPs were used to calculate the average daily doses (ADDs) of workers, according to the method described by the Environmental Protection Agency.Results: The number concentration (NC), mass concentration, surface area concentration, personal NC, and lung-deposited surface area concentration of submicron particles were &amp;gt;105 pt/cm3, 0.2–0.4 mg/m3, 600–1,200 μm2/cm3, 0.7–1.4 pt/cm3, and 100–700 μm2/cm3, respectively. The size distribution showed that the submicron particles mainly gathered between 30 and 200 nm. The health risk of submicron particles was high. Upon respiratory intake, most UFPs (111.5 mg) were inhaled into the lungs, a few UFPs (0.272 mg) were trapped in the nasal cavity, and a small minority of UFPs (0.292 mg) were deposited in the olfactory area. The ADD of male workers with 10 years of exposure in the olfactory area, nasal cavity, and lung were 1.192 × 10–3 mg/kg·d−1, 1.11 × 10–3 mg/kg·d−1, and 0.455 mg/kg·d−1, respectively.Conclusion: Owing to the high concentrations of submicron particles, the workers involved in the powder-coating process are at a high health risk. Moreover, the respiratory intake of UFPs by workers is high, which is suggested by the highly deposited dosage of UFPs in the lungs and the corresponding high ADD in workers. Control measures, including engineering control, management control, and personal protective equipment, must be improved for the protection of workers.

Deficits in peripheric and central olfactory measurements in smokers: evaluated by cranial MRI.

Cigarette smoking remains a serious health problem all over the world. We investigated the peripheral and central olfactory pathways in young male smokers to determine whether there is a relationship between the amount of cigarettes smoked and duration of smoking and the dimensions of the olfactory areas. In this retrospective study, cranial Magnetic Resonance Imaging (MRI) images of adult male smokers aged ≤ 40years (n = 51) and 50 healthy male adults were analyzed. The olfactory bulbus (OB) volumes and olfactory sulcus (OS) depths, insular gyrus, and corpus amygdala areas were measured via cranial MRI. In the smoker group, the number of cigarettes smoked and duration of smoking were noted and the Brinkmann index was calculated. OB volume, OS depth, and the insular gyrus areas of the smokers were lower than in the control group (p < 0.05). There were no differences between the groups in terms of the corpus amygdala measurements (p > 0.05). No significant correlations were found between the number of cigarettes smoked daily, smoking duration, and the Brinkmann index and the peripheral and central olfactory measurements in our study (p > 0.05). In smokers, OB volumes, the OS, and the central areas decrease bilaterally, regardless of smoking duration and number of cigarettes smoked daily. This could be related to inflammatory mediators that may be harmful to the olfactory neuroepithelium, gray matter atrophy in the brain, or endothelial damage related to smoking and its effects on blood support to the brain and olfactory regions.

Pre-referral intranasal artesunate powder for cerebral malaria: a proof-of-concept study

BackgroundMalaria still kills young children in rural endemic areas because early treatment is not available. Thus, the World Health Organization recommends the administration of artesunate suppositories as pre-referral treatment before transportation to the hospital in case of severe symptoms with an unavailable parenteral and oral treatment. However, negative cultural perception of the rectal route, and limited access to artesunate suppositories, could limit the use of artesunate suppositories. There is, therefore, a need for an alternative route for malaria pre-referral treatment. The aim of this study was to assess the potential of intranasal route for malaria pre-referral treatment.MethodsThe permeability of artesunate through human nasal mucosa was tested in vitro. The Transepithelial Electrical Resistance (TEER) of the nasal mucosa was followed during the permeation tests. Beside, regional deposition of artesunate powder was assessed with an unidose drug delivery device in each nostril of a nasal cast. Artesunate quantification was performed using Liquid Chromatography coupled to tandem Mass Spectrometry.ResultsThe experimental model of human nasal mucosa was successfully implemented. Using this model, artesunate powder showed a much better passage rate through human nasal mucosa than solution (26.8 ± 6.6% versus 2.1 ± 0.3%). More than half (62.3%) of the artesunate dose sprayed in the nostrils of the nasal cast was recovered in the olfactory areas (44.7 ± 8.6%) and turbinates (17.6 ± 3.3%) allowing nose-to-brain and systemic drug diffusion, respectively.ConclusionArtesunate powder showed a good permeation efficiency on human nasal mucosa. Moreover it can be efficiently sprayed in the nostrils using unidose device to reach the olfactory area leading to a fast nose-to-brain delivery as well as a systemic effect. Taken together, those results are part of the proof-of-concept for the use of intranasal artesunate as a malaria pre-referral treatment.

Respiratory epithelial adenomatoid hamartomas of the sinonasal tract: A histopathological analysis of 50 patients.

Respiratory epithelial adenomatoid hamartoma (REAH) is a benign lesion of the nasal cavity and paranasal sinuses. Here, we report the clinicopathological characteristics of REAH identified in 2065 cases with nasal/paranasal polypoid lesions treated with endoscopic sinus surgery (ESS) at our hospital from 2008 to 2021. Cases including the olfactory area were reviewed and 50 patients of REAH were identified pathologically (50/2065, 2.4%). The average age was 58.9 years old and the male/female ratio was 45/5. Grossly, REAH showed a whitish surface and elastic firm consistency. The histopathological characteristics included proliferation of small to medium-sized glands composed of ciliated respiratory epithelium containing goblet cells; thickening of the basement membrane compared to that for inverted papilloma (9.6 ± 2.4 vs. 1.3 ± 1.6 µm, p < 0.001); and no intra-epithelial neutrophilic infiltration. Among the REAH cases, 81% were associated with sinonasal inflammatory polyps. Many olfactory cleft polyps were REAH (38/98, 39%). The rate of REAH found in ESS in the last 7 years was higher than that in the first 7 years (3.17% vs. 1.62%, p = 0.032). Our results in Japanese patients are similar to those found in other countries, including male predominance. REAH is relatively common and that 39% of polyps taken from olfactory clefts are REAH.

Biochemical and Neuropathological Findings in a Creutzfeldt-Jakob Disease Patient with the Rare Val180Ile-129Val Haplotype in the Prion Protein Gene.

Genetic Creutzfeldt–Jakob disease (gCJD) associated with the V180I mutation in the prion protein (PrP) gene (PRNP) in phase with residue 129M is the most frequent cause of gCJD in East Asia, whereas it is quite uncommon in Caucasians. We report on a gCJD patient with the rare V180I-129V haplotype, showing an unusually long duration of the disease and a characteristic pathological PrP (PrPSc) glycotype. Family members carrying the mutation were fully asymptomatic, as commonly observed with this mutation. Neuropathological examination showed a lesion pattern corresponding to that commonly reported in Japanese V180I cases with vacuolization and gliosis of the cerebral cortexes, olfactory areas, hippocampus and amygdala. PrP was deposited with a punctate, synaptic-like pattern in the cerebral cortex, amygdala and olfactory tract. Western blot analyses of proteinase-K-resistant PrP showed the characteristic two-banding pattern of V180I gCJD, composed of mono- and un-glycosylated isoforms. In line with reports on other V180I cases in the literature, Real-Time Quaking Induced Conversion (RT-QuIC) analyses did not demonstrate the presence of seeding activity in the cerebrospinal fluid and olfactory mucosa, suggesting that this haplotype also may result in a reduced seeding efficiency of the pathological PrP. Further studies are required to understand the origin, penetrance, disease phenotype and transmissibility of 180I-129V haplotype in Caucasians.

Larger gray matter volumes in neuropsychiatric long-COVID syndrome

Neuropsychiatric symptoms are the most common sequelae of long-COVID. As accumulating evidence suggests an impact of survived SARS-CoV-2-infection on brain physiology, it is necessary to further investigate brain structural changes in relation to course and neuropsychiatric symptom burden in long-COVID.To this end, the present study investigated 3T-MRI scans from long-COVID patients suffering from neuropsychiatric symptoms (n = 30), and healthy controls (n = 20). Whole-brain comparison of gray matter volume (GMV) was conducted by voxel-based morphometry. To determine whether changes in GMV are predicted by neuropsychiatric symptom burden and/or initial severity of symptoms of COVID-19 and time since onset of COVID-19 stepwise linear regression analysis was performed.Significantly enlarged GMV in long-COVID patients was present in several clusters (spanning fronto-temporal areas, insula, hippocampus, amygdala, basal ganglia, and thalamus in both hemispheres) when compared to controls. Time since onset of COVID-19 was a significant regressor in four of these clusters with an inverse relationship. No associations with clinical symptom burden were found.GMV alterations in limbic and secondary olfactory areas are present in long-COVID patients and might be dynamic over time. Larger samples and longitudinal data in long-COVID patients are required to further clarify the mediating mechanisms between COVID-19, GMV and neuropsychiatric symptoms.

Ecological constraints on highly evolvable olfactory receptor genes and morphology in neotropical bats.

Although evolvability of genes and traits may promote specialization during species diversification, how ecology subsequently restricts such variation remains unclear. Chemosensation requires animals to decipher a complex chemical background to locate fitness-related resources, and thus the underlying genomic architecture and morphology must cope with constant exposure to a changing odorant landscape; detecting adaptation amidst extensive chemosensory diversity is an open challenge. In phyllostomid bats, an ecologically diverse clade that evolved plant visiting from a presumed insectivorous ancestor, the evolution of novel food detection mechanisms is suggested to be a key innovation, as plant-visiting species rely strongly on olfaction, supplementarily using echolocation. If this is true, exceptional variation in underlying olfactory genes and phenotypes may have preceded dietary diversification. We compared olfactory receptor (OR) genes sequenced from olfactory epithelium transcriptomes and olfactory epithelium surface area of bats with differing diets. Surprisingly, although OR evolution rates were quite variable and generally high, they are largely independent of diet. Olfactory epithelial surface area, however, is relatively larger in plant-visiting bats and there is an inverse relationship between OR evolution rates and surface area. Relatively larger surface areas suggest greater reliance on olfactory detection and stronger constraint on maintaining an already diverse OR repertoire. Instead of the typical case in which specialization and elaboration are coupled with rapid diversification of associated genes, here the relevant genes are already evolving so quickly that increased reliance on smell has led to stabilizing selection, presumably to maintain the ability to consistently discriminate among specific odorants-a potential ecological constraint on sensory evolution.

Nasal Sprays Containing Mometasone Furoate Can Be Used Prophylactically in COVID-19 Infection and Related Smell Disorders

Objective: We aimed to emphasize the possible beneficial effects of intranasal sprays containing mometasone furoate, especially for preventive treatment or supportive treatment in patients with olfactory disorders due to damage to the olfactory area, or for regular use in healthcare workers with a high risk of close contact.&#x0D; Methods: Preventive and therapeutic scientific studies are continuing around the world for viral spread and viral damage associated with the Coronavirus disease 2019 (COVID-19) pandemic. We investigated the attachment of the COVID-19 virus in the nose and entry into the body with the crystal structure of the spike and Angiotensin-Converting Enzyme 2 (ACE-2) proteins, a molecular docking study. This scientific study is the first in-silico study to investigate the possible antiviral effects of Mometasone furoate molecules on spike protein and to show the antiviral effect of mometasone furoate on COVID-19.&#x0D; Results: We think that nasal sprays containing mometasone furoate can be used prophylactically in patients with COVID-19 infection due to its antiviral effect, and it may be beneficial to use sprays containing mometasone furoate before the symptoms of upper respiratory tract infection begin in patients.&#x0D; Conclusions: The role of these molecules in the treatment of acute smell disorders associated with COVID-19 infection and their antiviral effects on coronavirus should be investigated by conducting extensive scientific studies on the subject.

Systemic Ghrelin Treatment Induces Rapid, Transient, and Asymmetric Changes in the Metabolic Activity of the Mouse Brain

Introduction: Ghrelin regulates a variety of functions by acting in the brain. The targets of ghrelin in the mouse brain have been mainly mapped using immunolabeling against c-Fos, a transcription factor used as a marker of cellular activation, but such analysis has several limitations. Here, we used positron emission tomography in mice to investigate the brain areas responsive to ghrelin. Methods: We analyzed in male mice the brain areas responsive to systemically injected ghrelin using positron emission tomography imaging of ¹⁸F-fluoro-2-deoxyglucose (¹⁸F-FDG) uptake, an indicator of metabolic rate. Additionally, we studied if systemic administration of fluorescent ghrelin or native ghrelin displays symmetric accessibility or induction of c-Fos, respectively, in the brain of male mice. Results: Ghrelin increased ¹⁸F-FDG uptake in few specific areas of the isocortex, striatum, pallidum, thalamus, and midbrain at 0–10-min posttreatment. At the 10–20 and 20–30 min posttreatment, ghrelin induced mixed changes in ¹⁸F-FDG uptake in specific areas of the isocortex, striatum, pallidum, thalamus, and midbrain, as well as in areas of the olfactory areas, hippocampal and retrohippocampal regions, hypothalamus, pons, medulla, and even the cerebellum. Ghrelin-induced changes in ¹⁸F-FDG uptake were transient and asymmetric. Systemically administrated fluorescent-ghrelin-labeled midline brain areas known to contain fenestrated capillaries and the hypothalamic arcuate nucleus, where a symmetric labeling was observed. Ghrelin treatment also induced a symmetric increased c-Fos labeling in the arcuate nucleus. Discussion/Conclusion: Systemically injected ghrelin transiently and asymmetrically affects the metabolic activity of the brain of male mice in a wide range of areas, in a food intake-independent manner. The neurobiological bases of such asymmetry seem to be independent of the accessibility of ghrelin into the brain.

Olfactory swab sampling optimization for α-synuclein aggregate detection in patients with Parkinson’s disease

BackgroundIn patients with Parkinson’s disease (PD), real-time quaking-induced conversion (RT-QuIC) detection of pathological α-synuclein (α-syn) in olfactory mucosa (OM) is not as accurate as in other α-synucleinopathies. It is unknown whether these variable results might be related to a different distribution of pathological α-syn in OM. Thus, we investigated whether nasal swab (NS) performed in areas with a different coverage by olfactory neuroepithelium, such as agger nasi (AN) and middle turbinate (MT), might affect the detection of pathological α-syn.MethodsNS was performed in 66 patients with PD and 29 non-PD between September 2018 and April 2021. In 43 patients, cerebrospinal fluid (CSF) was also obtained and all samples were analyzed by RT-QuIC for α-syn.ResultsIn the first round, 72 OM samples were collected by NS, from AN (NSAN) or from MT (NSMT), and 35 resulted positive for α-syn RT-QuIC, including 27/32 (84%) from AN, 5/11 (45%) from MT, and 3/29 (10%) belonging to the non-PD patients. Furthermore, 23 additional PD patients underwent NS at both AN and MT, and RT-QuIC revealed α-syn positive in 18/23 (78%) NSAN samples and in 10/23 (44%) NSMT samples. Immunocytochemistry of NS preparations showed a higher representation of olfactory neural cells in NSAN compared to NSMT. We also observed α-syn and phospho-α-syn deposits in NS from PD patients but not in controls. Finally, RT-QuIC was positive in 22/24 CSF samples from PD patients (92%) and in 1/19 non-PD.ConclusionIn PD patients, RT-QuIC sensitivity is significantly increased (from 45% to 84%) when NS is performed at AN, indicating that α-syn aggregates are preferentially detected in olfactory areas with higher concentration of olfactory neurons. Although RT-QuIC analysis of CSF showed a higher diagnostic accuracy compared to NS, due to the non-invasiveness, NS might be considered as an ancillary procedure for PD diagnosis.