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Lifestyle Genomics 2024Olfactory dysfunction (OD) is not uncommon following viral infection. Herein, we explore the interplay of host genetics with viral correlates in coronavirus disease 2019... (Review)
Review
Olfactory dysfunction (OD) is not uncommon following viral infection. Herein, we explore the interplay of host genetics with viral correlates in coronavirus disease 2019 (COVID-19)- and long COVID-related OD, and its diagnosis and treatment that remain challenging. Two genes associated with olfaction, UGT2A1 and UGT2A2, appear to be involved in COVID-19-related anosmia, a hallmark symptom of acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly in the early stages of the pandemic. SARS-CoV-2 infects olfactory support cells, sustentacular and Bowman gland cells, that surround olfactory sensory neurons (OSNs) in the olfactory epithelium (OE) where the initial step of odor detection takes place. Anosmia primarily arises from the infection of support cells of the OE, followed by the deciliation and disruption of OE integrity, typically without OSN infection. Through the projected axons of OSNs, the virus could theoretically reach the olfactory bulb and brain, but current evidence points against this route. Intriguingly, SARS-CoV-2 infection of support cells leads to profound alterations in the nuclear architecture of OSNs, leading to the downregulation of odorant receptor-related genes, e.g., of Adcy3. Viral factors associated with the development of OD include spike protein aminoacidic changes, e.g., D614G, the first substitution that was selected early during SARS-CoV-2 evolution. More recent variants of the Omicron family are less likely to cause OD compared to Delta or Alpha, although OD has been associated with a milder disease course. OD is one of the most prevalent post-acute neurologic symptoms of SARS-CoV-2 infection. The tens of millions of people worldwide who have lingering problems with OD wait eagerly for effective new treatments that will restore their sense of smell which adds value to their quality of life.
Topics: COVID-19; Humans; SARS-CoV-2; Olfaction Disorders; Anosmia; Post-Acute COVID-19 Syndrome; Olfactory Mucosa; Olfactory Receptor Neurons
PubMed: 38749402
DOI: 10.1159/000539292 -
Current Opinion in Otolaryngology &... Feb 2011To discuss the unique properties of the olfactory epithelium and the potential use of olfactory epithelial grafts to restore olfactory function. (Review)
Review
PURPOSE OF REVIEW
To discuss the unique properties of the olfactory epithelium and the potential use of olfactory epithelial grafts to restore olfactory function.
RECENT FINDINGS
Sensory neurons in the olfactory epithelium undergo continuous regeneration, grow new axons, and reestablish connections with the olfactory bulb throughout life. When transplanted into different regions of the brain, olfactory epithelial graft cells retain their morphological and regenerative properties. Olfactory cells within the grafts grow axons that enter into the surrounding brain tissue. Recent studies have shown that the olfactory epithelium can be grafted directly to the olfactory bulb.
SUMMARY
The olfactory epithelium has a remarkable capacity to continuously generate new sensory neurons and survives grafting into different regions of the brain. A review of the literature and the future use of olfactory grafts as a potential method to restore olfactory function is discussed.
Topics: Animals; Humans; Olfaction Disorders; Olfactory Mucosa; Smell
PubMed: 21102335
DOI: 10.1097/MOO.0b013e328341e242 -
Philosophical Transactions of the Royal... Dec 2000Zonal organization is one of the characteristic features observed in both main and accessory olfactory systems. In the main olfactory system, most of the odorant... (Review)
Review
Zonal organization is one of the characteristic features observed in both main and accessory olfactory systems. In the main olfactory system, most of the odorant receptors are classified into four groups according to their zonal expression patterns in the olfactory epithelium. Each group of odorant receptors is expressed by sensory neurons distributed within one of four circumscribed zones. Olfactory sensory neurons in a given zone of the epithelium project their axons to the glomeruli in a corresponding zone of the main olfactory bulb. Glomeruli in the same zone tend to represent similar odorant receptors having similar tuning specificity to odorants. Vomeronasal receptors (or pheromone receptors) are classified into two groups in the accessory olfactory system. Each group of receptors is expressed by vomeronasal sensory neurons in either the apical or basal zone of the vomeronasal epithelium. Sensory neurons in the apical zone project their axons to the rostral zone of the accessory olfactory bulb and form synaptic connections with mitral tufted cells belonging to the rostral zone. Signals originated from basal zone sensory neurons are sent to mitral tufted cells in the caudal zone of the accessory olfactory bulb. We discuss functional implications of the zonal organization in both main and accessory olfactory systems.
Topics: Animals; Axons; Chemoreceptor Cells; Humans; Mammals; Olfactory Bulb; Olfactory Mucosa; Perception; Receptors, Odorant; Vomeronasal Organ
PubMed: 11205342
DOI: 10.1098/rstb.2000.0736 -
BMC Neuroscience Sep 2007Smell is often regarded as an ancillary perception in primates, who seem so dominated by their sense of vision. In this paper, we will portray some aspects of the... (Review)
Review
Smell is often regarded as an ancillary perception in primates, who seem so dominated by their sense of vision. In this paper, we will portray some aspects of the significance of olfaction to human life and speculate on what evolutionary factors contribute to keeping it alive. We then outline the functional architecture of olfactory sensory neurons and their signal transduction pathways, which are the primary detectors that render olfactory perception possible. Throughout the phylogenetic tree, olfactory neurons, at their apical tip, are either decorated with cilia or with microvilli. The significance of this dichotomy is unknown. It is generally assumed that mammalian olfactory neurons are of the ciliary type only. The existence of so-called olfactory microvillar cells in mammals, however, is well documented, but their nature remains unclear and their function orphaned. This paper discusses the possibility, that in the main olfactory epithelium of mammals ciliated and microvillar sensory cells exist concurrently. We review evidence related to this hypothesis and ask, what function olfactory microvillar cells might have and what signalling mechanisms they use.
Topics: Animals; Cilia; Humans; Microvilli; Olfactory Mucosa; Olfactory Pathways; Olfactory Receptor Neurons; Signal Transduction; Smell
PubMed: 17903277
DOI: 10.1186/1471-2202-8-S3-S1 -
Inhalation Toxicology 2015Inhaled nanoparticles can migrate to the brain via the olfactory bulb, as demonstrated in experiments in several animal species. This route of exposure may be the...
CONTEXT
Inhaled nanoparticles can migrate to the brain via the olfactory bulb, as demonstrated in experiments in several animal species. This route of exposure may be the mechanism behind the correlation between air pollution and human neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease.
OBJECTIVES
This article aims to (i) estimate the dose of inhaled nanoparticles that deposit in the human olfactory epithelium during nasal breathing at rest and (ii) compare the olfactory dose in humans with our earlier dose estimates for rats.
MATERIALS AND METHODS
An anatomically-accurate model of the human nasal cavity was developed based on computed tomography scans. The deposition of 1-100 nm particles in the whole nasal cavity and its olfactory region were estimated via computational fluid dynamics (CFD) simulations. Our CFD methods were validated by comparing our numerical predictions for whole-nose deposition with experimental data and previous CFD studies in the literature.
RESULTS
In humans, olfactory dose of inhaled nanoparticles is highest for 1-2 nm particles with ∼1% of inhaled particles depositing in the olfactory region. As particle size grows to 100 nm, olfactory deposition decreases to 0.01% of inhaled particles.
DISCUSSION AND CONCLUSION
Our results suggest that the percentage of inhaled particles that deposit in the olfactory region is lower in humans than in rats. However, olfactory dose per unit surface area is estimated to be higher in humans in the 1--7 nm size range due to the larger inhalation rate in humans. These dose estimates are important for risk assessment and dose-response studies investigating the neurotoxicity of inhaled nanoparticles.
Topics: Adult; Animals; Computer Simulation; Disease Models, Animal; Female; Humans; Hydrodynamics; Inhalation Exposure; Male; Middle Aged; Models, Anatomic; Nanoparticles; Nasal Cavity; Nose; Olfactory Bulb; Olfactory Mucosa; Particle Size; Rats; Rats, Inbred F344; Reproducibility of Results
PubMed: 26194036
DOI: 10.3109/08958378.2015.1066904 -
Anatomical Record (Hoboken, N.J. : 2007) Jan 2021Nasal turbinals, delicate and complex bones of the nasal cavity that support respiratory or olfactory mucosa (OM), are now easily studied using high resolution...
Nasal turbinals, delicate and complex bones of the nasal cavity that support respiratory or olfactory mucosa (OM), are now easily studied using high resolution micro-computed tomography (μ-CT). Standard μ-CT currently lacks the capacity to identify OM or other mucosa types without additional radio-opaque staining techniques. However, even unstained mucosa is more radio-opaque than air, and thus mucosal thickness can be discerned. Here, we assess mucosal thickness of the nasal fossa using the cranium of a cadaveric adult dog that was μ-CT scanned with an isotropic resolution of 30 μm, and subsequently histologically sectioned and stained. After co-alignment of μ-CT slice planes to that of histology, mucosal thickness was estimated at four locations. Results based on either μ-CT or histology indicate olfactory mucosa is thicker on average compared with non-olfactory mucosa (non-OM). In addition, olfactory mucosa has a lesser degree of variability than the non-OM. Variability in the latter appears to relate mostly to the varying degree of vascularity of the lamina propria. Because of this, in structures with both specialized vascular respiratory mucosa and OM, such as the first ethmoturbinal (ET I), the range of thickness of OM and non-OM may overlap. Future work should assess the utility of diffusible iodine-based contrast enhanced CT techniques, which can differentiate epithelium from the lamina propria, to enhance our ability to differentiate mucosa types on more rostral ethmoturbinals. This is especially critical for structures such as ET I, which have mixed functional roles in many mammals.
Topics: Animals; Dogs; Nasal Cavity; Olfactory Mucosa; X-Ray Microtomography
PubMed: 32959987
DOI: 10.1002/ar.24511 -
Current Protocols in Neuroscience Jan 2012Olfactory sensory neurons, located in the nasal epithelium, detect and transmit odorant information to the central nervous system. This requires that these neurons form...
Olfactory sensory neurons, located in the nasal epithelium, detect and transmit odorant information to the central nervous system. This requires that these neurons form specific neuronal connections within the olfactory bulb and express receptors and signaling molecules specific for these functions. This protocol describes a primary olfactory sensory neuron culture technique that allows in vitro investigation of olfactory sensory neuron differentiation, axon outgrowth, odorant receptor expression, and function. Olfactory epithelium is obtained from the nasal cavity and is enzymatically treated to reduce stroma tissue. Dissociated olfactory sensory neurons are cultured directly on a layer of cortical astrocytes to support their survival. Using this method, cultured olfactory sensory neurons maintain their bipolar morphology and express odorant signal transduction molecules, which are specific for olfactory sensory neurons.
Topics: Animals; Cell Culture Techniques; Mice; Olfactory Mucosa; Sensory Receptor Cells
PubMed: 23042501
DOI: 10.1002/0471142301.ns0324s58 -
Neurotoxicology Dec 2018Fish rely heavily on their sense of smell to maintain behaviors essential for survival, such as predator detection and avoidance, prey selection, social behavior,...
Fish rely heavily on their sense of smell to maintain behaviors essential for survival, such as predator detection and avoidance, prey selection, social behavior, imprinting, and homing to natal streams and spawning sites. Due to its direct contact with the outside environment, the peripheral olfactory system of fish is particularly susceptible to dissolved contaminants. In particular, environmental exposures to copper (Cu) can cause a rapid loss of olfactory function. In this study, confocal imaging of double-transgenic zebrafish larvae with differentially labeled ciliated and microvillous olfactory sensory neurons (OSNs) were used to examine cell death and regeneration following Cu exposure. Changes in cell morphologies were observed at varying degrees within both ciliated and microvillous OSNs, including the presence of round dense cell bodies, cell loss and fragmentation, retraction or loss of axons, disorganized cell arrangements, and loss of cells and fluorescence signal intensity, which are all indicators of cell death after Cu exposure. A marked loss of ciliated OSNs relative to microvillous OSNs occurred after exposure to low Cu concentrations for 3 h, with some regeneration observed after 72 h. At higher Cu concentrations and 24-h exposures, ciliated and microvillous OSNs were damaged with increased severity of injury with longer Cu exposures. Interestingly, microvillous, but not ciliated OSNs, regenerated rapidly within the 72-h time period of recovery after death from Cu exposure, suggesting that microvillous OSNs may be replaced in lieu of ciliated OSNs. An increase in bromodeoxyuridine labeling was observed 24 h after Cu-induced OSN death, suggesting that increased proliferation of the olfactory stem cells replaced the damaged OSNs. Olfactory behavioral analyses supported our imaging studies and revealed both initial loss and restoration of olfactory function after Cu exposures. In summary, our studies indicate that following zebrafish OSN damage by Cu, regeneration of microvillous OSNs may occur exceeding ciliated OSNs, likely via increased proliferation of the cellular reservoir of neuronal OSC precursors. Transgenic zebrafish are a valuable tool to study metal olfactory injury and recovery and to characterize sensitive olfactory neuron populations in fish exposed to environmental pollutants.
Topics: Animals; Animals, Genetically Modified; Cell Death; Cell Proliferation; Copper; Larva; Nerve Regeneration; Odorants; Olfactory Mucosa; Olfactory Receptor Neurons; Random Allocation; Smell; Water Pollutants, Chemical; Zebrafish
PubMed: 30292653
DOI: 10.1016/j.neuro.2018.10.002 -
The Laryngoscope Aug 2011The pathophysiology underlying human olfactory disorders is poorly understood because biopsying the olfactory epithelium (OE) can be unrepresentative and extensive...
OBJECTIVES/HYPOTHESIS
The pathophysiology underlying human olfactory disorders is poorly understood because biopsying the olfactory epithelium (OE) can be unrepresentative and extensive immunohistochemical analysis is lacking. Autopsy tissue enriches our grasp of normal and abnormal olfactory immunohistology and guides the sampling of the OE by biopsy. Furthermore, a comparison of the molecular phenotype of olfactory epithelial cells between rodents and humans will improve our ability to correlate human histopathology with olfactory dysfunction.
STUDY DESIGN
An immunohistochemical analysis of human olfactory tissue using a comprehensive battery of proven antibodies.
METHODS
Human olfactory mucosa obtained from 21 autopsy specimens was analyzed with immunohistochemistry. The position and extent of olfactory mucosa was assayed by staining whole mounts (WMs) with neuronal markers. Sections of the OE were analyzed with an extensive group of antibodies directed against cytoskeletal proteins and transcription factors, as were surgical specimens from an esthesioneuroblastoma.
RESULTS
Neuron-rich epithelium is always found inferior to the cribriform plate, even at advanced age, despite the interruptions in the neuroepithelial sheet caused by patchy respiratory metaplasia. The pattern of immunostaining with our antibody panel identifies two distinct types of basal cell progenitors in human OE similar to rodents. The panel also clarifies the complex composition of esthesioneuroblastoma.
CONCLUSIONS
The extent of human olfactory mucosa at autopsy can easily be delineated as a function of age and neurologic disease. The similarities in human versus rodent OE will enable us to translate knowledge from experimental animals to humans and will extend our understanding of human olfactory pathophysiology.
Topics: Aged; Aged, 80 and over; Cytoskeletal Proteins; Esthesioneuroblastoma, Olfactory; Female; Glycoproteins; Humans; Immunohistochemistry; Male; Middle Aged; Olfactory Mucosa; Transcription Factors
PubMed: 21792956
DOI: 10.1002/lary.21856 -
Iranian Biomedical Journal Oct 2008Olfactory ensheathing glia (OEG) has been shown to have a neuroprotective effect after being transplanted in rats with spinal cord injury. This study was conducted to...
BACKGROUND
Olfactory ensheathing glia (OEG) has been shown to have a neuroprotective effect after being transplanted in rats with spinal cord injury. This study was conducted to determine the possible beneficial results of olfactory mucosa transplantation (OMT) which is a source of OEG on functional recovery and axonal regeneration after transection of the sciatic nerve.
METHODS
In this study, 36 adult female Sprague-Dawley rats were used. The sciatic nerve was transected in 24 rats and immediately repaired by sciatic-sciatic anastomosis, and randomly divided equally into two groups. The experimental group received the OMT at the transected site and the control group received the respiratory mucosa transplant. In another twelve rats as sham-operated animals, the sciatic nerve was exposed but no transection was made. DiI retrograde tracing was injected in the gastrocnemius muscle two months after surgery to allow visualization of the extent of axonal regeneration. Functional recovery was also assessed at 15, 30, 45 and 60 days after surgery using walking track analysis and sciatic function index (SFI) calculations.
RESULTS
The total number of DiI labeled motorneurones in the ventral horn (L4-L6) and the SFI scores were significantly higher in the group of rats that received olfactory mucosa rather than respiratory mucosa.
CONCLUSIONS
The outcome indicates that olfactory mucosa is a useful treatment to improve nerve regeneration in mammals with peripheral nerve injury.
Topics: Animals; Behavior, Animal; Female; Neurogenesis; Olfactory Mucosa; Rats; Rats, Sprague-Dawley
PubMed: 19079532
DOI: No ID Found