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BMC Biology Dec 2023Olfactory sensory neurons detect odourants via multiple long cilia that protrude from their dendritic endings. The G protein-coupled receptor GPRC5C was identified as...
BACKGROUND
Olfactory sensory neurons detect odourants via multiple long cilia that protrude from their dendritic endings. The G protein-coupled receptor GPRC5C was identified as part of the olfactory ciliary membrane proteome, but its function and localization is unknown.
RESULTS
High-resolution confocal and electron microscopy revealed that GPRC5C is located at the base of sensory cilia in olfactory neurons, but not in primary cilia of immature neurons or stem cells. Additionally, GPRC5C localization in sensory cilia parallels cilia formation and follows the formation of the basal body. In closer examination, GPRC5C was found in the ciliary transition zone. GPRC5C deficiency altered the structure of sensory cilia and increased ciliary layer thickness. However, primary cilia were unaffected. Olfactory sensory neurons from Gprc5c-deficient mice exhibited altered localization of olfactory signalling cascade proteins, and of ciliary phosphatidylinositol-4,5-bisphosphat. Sensory neurons also exhibited increased neuronal activity as well as altered mitochondrial morphology, and knockout mice had an improved ability to detect food pellets based on smell.
CONCLUSIONS
Our study shows that GPRC5C regulates olfactory cilia composition and length, thereby controlling odour perception.
Topics: Animals; Mice; Cilia; Mice, Knockout; Odorants; Olfactory Receptor Neurons; Receptors, G-Protein-Coupled; Smell
PubMed: 38110903
DOI: 10.1186/s12915-023-01790-0 -
Journal of Agricultural and Food... Jun 2023Flavor is perceived through the olfactory, taste, and trigeminal systems, mediated by designated GPCRs and channels. Signal integration occurs mainly in the brain, but...
Flavor is perceived through the olfactory, taste, and trigeminal systems, mediated by designated GPCRs and channels. Signal integration occurs mainly in the brain, but some cross-reactivities occur at the receptor level. Here, we predict potential bitterness and taste receptors targets for thousands of odorants. BitterPredict and BitterIntense classifiers suggest that 3-9% of flavor and food odorants have bitter taste, but almost none are intensely bitter. About 14% of bitter molecules are expected to have an odor. Bitterness is more common for unpleasant smells such as fishy, amine, and ammoniacal, while non-bitter odorants often have pleasant smells. Experimental toxicity values suggest that fishy ammoniac smells are more toxic than pleasant smells, regardless of bitterness. TAS2R14 is predicted as the main bitter receptor for odorants, confirmed by profiling of 10 odorants. The activity of bitter odorants may have implications for physiology due to ectopic expression of taste and smell receptors.
Topics: Humans; Taste; Odorants; Taste Perception; Smell; Olfactory Receptor Neurons; Receptors, G-Protein-Coupled
PubMed: 37263600
DOI: 10.1021/acs.jafc.3c00592 -
EBioMedicine Mar 2023Zika virus (ZIKV) is an emerging arbovirus of the genus flavivirus that is associated with congenital Zika syndrome (CZS) in newborns. A wide range of clinical symptoms...
BACKGROUND
Zika virus (ZIKV) is an emerging arbovirus of the genus flavivirus that is associated with congenital Zika syndrome (CZS) in newborns. A wide range of clinical symptoms including intellectual disability, speech delay, coordination or movement problems, and hearing and vision loss, have been well documented in children with CZS. However, whether ZIKV can invade the olfactory system and lead to post-viral olfactory dysfunction (PVOD) remains unknown.
METHODS
We investigated the susceptibility and biological responses of the olfactory system to ZIKV infection using mouse models and human olfactory organoids derived from patient olfactory mucosa.
FINDINGS
We demonstrate that neonatal mice infected with ZIKV suffer from transient olfactory dysfunction when they reach to puberty. Moreover, ZIKV mainly targets olfactory ensheathing cells (OECs) and exhibits broad cellular tropism colocalizing with small populations of mature/immature olfactory sensory neurons (mOSNs/iOSNs), sustentacular cells and horizontal basal cells in the olfactory mucosa (OM) of immunodeficient AG6 mice. ZIKV infection induces strong antiviral immune responses in both the olfactory mucosa and olfactory bulb tissues, resulting in the upregulation of proinflammatory cytokines/chemokines and genes related to the antiviral response. Histopathology and transcriptomic analysis showed typical tissue damage in the olfactory system. Finally, by using an air-liquid culture system, we showed that ZIKV mainly targets sustentacular cells and OECs and support robust ZIKV replication.
INTERPRETATION
Our results demonstrate that olfactory system represents as significant target for ZIKV infection, and that PVOD may be neglected in CZS patients.
FUNDING
Stated in the acknowledgment.
Topics: Infant, Newborn; Child; Humans; Mice; Animals; Zika Virus; Zika Virus Infection; Virus Replication; Antiviral Agents; Olfaction Disorders
PubMed: 36739631
DOI: 10.1016/j.ebiom.2023.104457 -
Neuron Dec 2021The convergent evolution of the fly and mouse olfactory system led us to ask whether the anatomic connectivity and functional logic of olfactory circuits would evolve in...
The convergent evolution of the fly and mouse olfactory system led us to ask whether the anatomic connectivity and functional logic of olfactory circuits would evolve in artificial neural networks trained to perform olfactory tasks. Artificial networks trained to classify odor identity recapitulate the connectivity inherent in the olfactory system. Input units are driven by a single receptor type, and units driven by the same receptor converge to form a glomerulus. Glomeruli exhibit sparse, unstructured connectivity onto a larger expansion layer of Kenyon cells. When trained to both classify odor identity and to impart innate valence onto odors, the network develops independent pathways for identity and valence classification. Thus, the defining features of fly and mouse olfactory systems also evolved in artificial neural networks trained to perform olfactory tasks. This implies that convergent evolution reflects an underlying logic rather than shared developmental principles.
Topics: Animals; Machine Learning; Mice; Odorants; Olfactory Bulb; Olfactory Pathways; Olfactory Perception; Olfactory Receptor Neurons; Smell
PubMed: 34619093
DOI: 10.1016/j.neuron.2021.09.010 -
Frontiers in Immunology 2023The Coronavirus Disease 2019 (COVID-19) is mainly a respiratory syndrome that can affect multiple organ systems, causing a variety of symptoms. Among the most common and...
INTRODUCTION
The Coronavirus Disease 2019 (COVID-19) is mainly a respiratory syndrome that can affect multiple organ systems, causing a variety of symptoms. Among the most common and characteristic symptoms are deficits in smell and taste perception, which may last for weeks/months after COVID-19 diagnosis owing to mechanisms that are not fully elucidated.
METHODS
In order to identify the determinants of olfactory symptom persistence, we obtained olfactory mucosa (OM) from 21 subjects, grouped according to clinical criteria: i) with persistent olfactory symptoms; ii) with transient olfactory symptoms; iii) without olfactory symptoms; and iv) non-COVID-19 controls. Cells from the olfactory mucosa were harvested for transcriptome analyses.
RESULTS AND DISCUSSION
RNA-Seq assays showed that gene expression levels are altered for a long time after infection. The expression profile of micro RNAs appeared significantly altered after infection, but no relationship with olfactory symptoms was found. On the other hand, patients with persistent olfactory deficits displayed increased levels of expression of genes involved in the inflammatory response and zinc homeostasis, suggesting an association with persistent or transient olfactory deficits in individuals who experienced infection.
PubMed: 37520523
DOI: 10.3389/fimmu.2023.1148595 -
Frontiers in Neural Circuits 2024The olfactory epithelium (OE) is directly exposed to environmental agents entering the nasal cavity, leaving OSNs prone to injury and degeneration. The causes of... (Review)
Review
The olfactory epithelium (OE) is directly exposed to environmental agents entering the nasal cavity, leaving OSNs prone to injury and degeneration. The causes of olfactory dysfunction are diverse and include head trauma, neurodegenerative diseases, and aging, but the main causes are chronic rhinosinusitis (CRS) and viral infections. In CRS and viral infections, reduced airflow due to local inflammation, inflammatory cytokine production, release of degranulated proteins from eosinophils, and cell injury lead to decreased olfactory function. It is well known that injury-induced loss of mature OSNs in the adult OE causes massive regeneration of new OSNs within a few months through the proliferation and differentiation of progenitor basal cells that are subsequently incorporated into olfactory neural circuits. Although normal olfactory function returns after injury in most cases, prolonged olfactory impairment and lack of improvement in olfactory function in some cases poses a major clinical problem. Persistent inflammation or severe injury in the OE results in morphological changes in the OE and respiratory epithelium and decreases the number of mature OSNs, resulting in irreversible loss of olfactory function. In this review, we discuss the histological structure and distribution of the human OE, and the pathogenesis of olfactory dysfunction associated with CRS and viral infection.
Topics: Humans; Olfactory Mucosa; Olfaction Disorders; Olfactory Receptor Neurons; Sinusitis; Rhinitis; Animals
PubMed: 38903957
DOI: 10.3389/fncir.2024.1406218 -
European Annals of Otorhinolaryngology,... Jan 2022The concept of ethmoidal sinuses composed of ethmoidal air cells does not appear to fit with the embryological origin of the ethmoid. Post-natal formation of the...
The concept of ethmoidal sinuses composed of ethmoidal air cells does not appear to fit with the embryological origin of the ethmoid. Post-natal formation of the paranasal sinuses, as visualized by MRI, appears to be fundamentally different from the embryological development of the ethmoid sinus. These two organs also appear to have very distinct functions: paranasal sinuses play a role in respiration and sanitization of the respiratory tract, while the ethmoid sinus plays a role in olfaction. However, human acquisition of bipedalism resulted in ethmoidal compartmentalization into olfactory clefts lined by olfactory mucosa and the ethmoidal labyrinth formed by a meshwork of ethmoturbinals that have lost their olfactory mucosa. Ethmoturbinals are septa that increase the surface area of olfactory mucosa in mammalian olfactory chambers. Embryological development of the human ethmoid sinus can be seen as the result of curved stacking of ethmoturbinal septa forming passages. Surgically, these passages can be accessed via the middle, superior and supreme meati. An ethmoidectomy technique following the ethmoturbinal passages can therefore be described. This structure of the ethmoidal labyrinth is both useful and necessary for the teaching of ethmoidal surgery.
Topics: Animals; Ethmoid Bone; Ethmoid Sinus; Humans; Paranasal Sinuses; Smell
PubMed: 33931331
DOI: 10.1016/j.anorl.2021.04.005 -
Nature Communications Jul 2022Birds, reptiles and insects have the ability to discriminate humidity levels that influence their survival and geographic distribution. Insects are particularly...
Birds, reptiles and insects have the ability to discriminate humidity levels that influence their survival and geographic distribution. Insects are particularly susceptible to humidity changes due to high surface area to volume ratios, but it remains unclear how humidity sensors transduce humidity signals. Here we identified Or42b-expressing olfactory sensory neurons, which are required for moisture attraction in Drosophila. The sensilla housing Or42b neurons show cuticular deformations upon moist air stimuli, indicating a conversion of humidity into mechanical force. Accordingly, we found Or42b neurons directly respond to humidity changes and rely on the mechanosensitive ion channel TMEM63 to mediate humidity sensing (hygrosensation). Expressing human TMEM63B in Tmem63 mutant flies rescued their defective phenotype in moisture attraction, demonstrating functional conservation. Thus, our results reveal a role of Tmem63 in hygrosensation and support the strategy to detect humidity by transforming it into a mechanical stimulus, which is unique in sensory transduction.
Topics: Animals; Drosophila; Drosophila Proteins; Humidity; Insecta; Olfactory Receptor Neurons; Sensilla
PubMed: 35780140
DOI: 10.1038/s41467-022-31253-z -
International Journal of Molecular... Apr 2022Olfactory function, orchestrated by the cells of the olfactory mucosa at the rooftop of the nasal cavity, is disturbed early in the pathogenesis of Alzheimer's disease...
Olfactory function, orchestrated by the cells of the olfactory mucosa at the rooftop of the nasal cavity, is disturbed early in the pathogenesis of Alzheimer's disease (AD). Biometals including zinc and calcium are known to be important for sense of smell and to be altered in the brains of AD patients. Little is known about elemental homeostasis in the AD patient olfactory mucosa. Here we aimed to assess whether the disease-related alterations to biometal homeostasis observed in the brain are also reflected in the olfactory mucosa. We applied RNA sequencing to discover gene expression changes related to metals in olfactory mucosal cells of cognitively healthy controls, individuals with mild cognitive impairment and AD patients, and performed analysis of the elemental content to determine metal levels. Results demonstrate that the levels of zinc, calcium and sodium are increased in the AD olfactory mucosa concomitantly with alterations to 17 genes related to metal-ion binding or metal-related function of the protein product. A significant elevation in alpha-2-macroglobulin, a known metal-binding biomarker correlated with brain disease burden, was observed on the gene and protein levels in the olfactory mucosa cells of AD patients. These data demonstrate that the olfactory mucosa cells derived from AD patients recapitulate certain impairments of biometal homeostasis observed in the brains of patients.
Topics: Alzheimer Disease; Calcium; Chelating Agents; Humans; Olfactory Mucosa; Trace Elements; Zinc
PubMed: 35456941
DOI: 10.3390/ijms23084123 -
Alzheimer's & Dementia : the Journal of... Feb 2024We assessed TAR DNA-binding protein 43 (TDP-43) seeding activity and aggregates detection in olfactory mucosa of patients with frontotemporal lobar degeneration with...
INTRODUCTION
We assessed TAR DNA-binding protein 43 (TDP-43) seeding activity and aggregates detection in olfactory mucosa of patients with frontotemporal lobar degeneration with TDP-43-immunoreactive pathology (FTLD-TDP) by TDP-43 seeding amplification assay (TDP43-SAA) and immunocytochemical analysis.
METHODS
The TDP43-SAA was optimized using frontal cortex samples from 16 post mortem cases with FTLD-TDP, FTLD with tau inclusions, and controls. Subsequently, olfactory mucosa samples were collected from 17 patients with FTLD-TDP, 15 healthy controls, and three patients carrying MAPT variants.
RESULTS
TDP43-SAA discriminated with 100% accuracy post mortem cases presenting or lacking TDP-43 neuropathology. TDP-43 seeding activity was detectable in the olfactory mucosa, and 82.4% of patients with FTLD-TDP tested positive, whereas 86.7% of controls tested negative (P < 0.001). Two out of three patients with MAPT mutations tested negative. In TDP43-SAA positive samples, cytoplasmatic deposits of phosphorylated TDP-43 in the olfactory neural cells were detected.
DISCUSSION
TDP-43 aggregates can be detectable in olfactory mucosa, suggesting that TDP43-SAA might be useful for identifying and monitoring FTLD-TDP in living patients.
Topics: Humans; Frontotemporal Dementia; Frontotemporal Lobar Degeneration; tau Proteins; Frontal Lobe; Neurons; DNA-Binding Proteins
PubMed: 37908186
DOI: 10.1002/alz.13541