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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 -
Annals of the New York Academy of... Jul 2009Odorant receptors are thought to be critical determinants of olfactory sensory neuron axon targeting and organization. Nonetheless, a systematic characterization of the... (Review)
Review
Odorant receptors are thought to be critical determinants of olfactory sensory neuron axon targeting and organization. Nonetheless, a systematic characterization of the onset of odorant receptor expression has not yet been done in the main olfactory epithelium. Here, we briefly review our current understanding regarding the onset of odorant receptor expression in the main olfactory epithelium and identify some of those questions which we believe must be of high priority for future study.
Topics: Animals; Olfactory Mucosa; Receptors, Odorant
PubMed: 19686100
DOI: 10.1111/j.1749-6632.2009.04366.x -
PloS One 2011Olfactory ensheathing cells (OECs) represent an interesting candidate for cell therapy and could be obtained from olfactory mucosa (OM-OECs) or olfactory bulbs...
Olfactory ensheathing cells (OECs) represent an interesting candidate for cell therapy and could be obtained from olfactory mucosa (OM-OECs) or olfactory bulbs (OB-OECs). Recent reports suggest that, depending on their origin, OECs display different functional properties. We show here the complementary and additive effects of co-transplanting OM-OECs and OB-OECs after lesion of a peripheral nerve. For this, a selective motor denervation of the laryngeal muscles was performed by a section/anastomosis of the recurrent laryngeal nerve (RLN). Two months after surgery, recovery of the laryngeal movements and synkinesis phenonema were analyzed by videolaryngoscopy. To complete these assessments, measure of latency and potential duration were determined by electrophysiological recordings and myelinated nerve fiber profiles were defined based on toluidine blue staining. To explain some of the mechanisms involved, tracking of GFP positive OECs was performed. It appears that transplantation of OM-OECs or OB-OECs displayed opposite abilities to improve functional recovery. Indeed, OM-OECs increased recuperation of laryngeal muscles activities without appropriate functional recovery. In contrast, OB-OECs induced some functional recovery by enhancing axonal regrowth. Importantly, co-transplantation of OM-OECs and OB-OECs supported a major functional recovery, with reduction of synkinesis phenomena. This study is the first which clearly demonstrates the complementary and additive properties of OECs obtained from olfactory mucosa and olfactory bulb to improve functional recovery after transplantation in a nerve lesion model.
Topics: Animals; Electromyography; Laryngoscopy; Male; Nerve Regeneration; Olfactory Bulb; Olfactory Mucosa; Peripheral Nerves; Peripheral Nervous System Diseases; Rats; Sciatic Neuropathy
PubMed: 21826209
DOI: 10.1371/journal.pone.0022816 -
Ecotoxicology and Environmental Safety Dec 2021Olfactory epithelial cells are in direct contact with myriad environmental contaminants which may consequently disrupt their structure and function. Copper ions (Cu) and...
Olfactory epithelial cells are in direct contact with myriad environmental contaminants which may consequently disrupt their structure and function. Copper ions (Cu) and copper nanoparticles (CuNPs) are two types of olfactory neurotoxicants. However, their effects on the structure of olfactory epithelium are largely uninvestigated. The density of olfactory goblet cells in CuNP- and Cu - exposed rainbow trout was assessed using light microscopy throughout time. In both copper (Cu) treatments, the number of goblet cells increased initially over the 24 h exposure and then recovered to normal throughout the 96 h exposure. These data suggested the 96 h exposure to Cu contaminants interfered with protective barrier provided by goblet cells. Nonetheless, lamellar and epithelial thickness of olfactory rosette did not change in the Cu-exposed fish. The gene transcript profile of olfactory mucosa studied by RNA-seq indicated Cu and CuNPs differentially targeted the molecular composition of cell junctions. In the Cu treatment, reduced mRNA abundances of tight junctions, adherens junction, desmosomes and hemidesmosomes, suggest that Cu-exposed olfactory mucosal cells had weak junctional complexes. In the CuNP treatment, on the other hand, the transcript abundances of cell junction compositions, except adherens junction, were upregulated. Transcripts associated with gap junctional channels were increased in both Cu treatments. The elevated transcript levels of gap junctions in both Cu treatments suggested that the demand for intercellular communication was increased in the Cu-exposed olfactory mucosa. Overall, our findings suggested that Cu induced greater adverse effects on the molecular composition of olfactory cell junctions relative to CuNPs. Impairment of junctional complexes may disrupt the structural integrity of olfactory mucosa.
Topics: Animals; Copper; Ions; Nanoparticles; Olfactory Mucosa; Oncorhynchus mykiss; Water Pollutants, Chemical
PubMed: 34634597
DOI: 10.1016/j.ecoenv.2021.112876 -
PloS One 2022The aim of the present study is to detect the presence of SARS-CoV-2 of patients affected by COVID-19 in olfactory mucosa (OM), sampled with nasal brushing (NB) and...
The aim of the present study is to detect the presence of SARS-CoV-2 of patients affected by COVID-19 in olfactory mucosa (OM), sampled with nasal brushing (NB) and biopsy, and to assess whether a non-invasive procedure, such as NB, might be used as a large-scale procedure for demonstrating SARS-CoV-2 presence in olfactory neuroepithelium. Nasal brushings obtained from all the COVID-19 patients resulted positive to SARS-CoV-2 immunocytochemistry while controls were negative. Double immunofluorescence showed that SARS-CoV-2 positive cells included supporting cells as well as olfactory neurons and basal cells. OM biopsies showed an uneven distribution of SARS-CoV-2 positivity along the olfactory neuroepithelium, while OM from controls were negative. SARS-CoV-2 was distinctively found in sustentacular cells, olfactory neurons, and basal cells, supporting what was observed in NB. Ultrastructural analysis of OM biopsies showed SARS-CoV-2 viral particles in the cytoplasm of sustentacular cells. This study shows the presence of SARS-CoV-2 at the level of the olfactory neuroepithelium in patients affected by COVID-19. For the first time, we used NB as a rapid non-invasive tool for assessing a potential neuroinvasion by SARS-CoV-2 infection.
Topics: Biopsy; COVID-19; Humans; Olfactory Mucosa; SARS-CoV-2
PubMed: 35413071
DOI: 10.1371/journal.pone.0266740 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Apr 2020The olfactory epithelium(OE) is the neuro-epithelial tissue that can be regenerated after damage in the nervous system. However, certain factors, such as... (Review)
Review
The olfactory epithelium(OE) is the neuro-epithelial tissue that can be regenerated after damage in the nervous system. However, certain factors, such as neurodegenerative diseases, head trauma, viral infections, etc. , can lead to olfactory dysfunction, affecting patients' physical and mental health, quality of life and risk identification, and even increase patient mortality. Therefore, it is important to clarify the mechanism of OE regeneration regulation and to find new treatment methods. This review is based on OE and the composition of olfactory stem cells, physiological and pathological olfactory sensory neurons regeneration regulation and treatment of olfactory disorders.
Topics: Humans; Olfactory Mucosa; Olfactory Receptor Neurons; Quality of Life; Regeneration; Smell
PubMed: 32842240
DOI: 10.13201/j.issn.2096-7993.2020.04.024 -
The Lancet. Neurology Sep 2021The mechanisms by which any upper respiratory virus, including SARS-CoV-2, impairs chemosensory function are not known. COVID-19 is frequently associated with olfactory... (Review)
Review
BACKGROUND
The mechanisms by which any upper respiratory virus, including SARS-CoV-2, impairs chemosensory function are not known. COVID-19 is frequently associated with olfactory dysfunction after viral infection, which provides a research opportunity to evaluate the natural course of this neurological finding. Clinical trials and prospective and histological studies of new-onset post-viral olfactory dysfunction have been limited by small sample sizes and a paucity of advanced neuroimaging data and neuropathological samples. Although data from neuropathological specimens are now available, neuroimaging of the olfactory system during the acute phase of infection is still rare due to infection control concerns and critical illness and represents a substantial gap in knowledge.
RECENT DEVELOPMENTS
The active replication of SARS-CoV-2 within the brain parenchyma (ie, in neurons and glia) has not been proven. Nevertheless, post-viral olfactory dysfunction can be viewed as a focal neurological deficit in patients with COVID-19. Evidence is also sparse for a direct causal relation between SARS-CoV-2 infection and abnormal brain findings at autopsy, and for trans-synaptic spread of the virus from the olfactory epithelium to the olfactory bulb. Taken together, clinical, radiological, histological, ultrastructural, and molecular data implicate inflammation, with or without infection, in either the olfactory epithelium, the olfactory bulb, or both. This inflammation leads to persistent olfactory deficits in a subset of people who have recovered from COVID-19. Neuroimaging has revealed localised inflammation in intracranial olfactory structures. To date, histopathological, ultrastructural, and molecular evidence does not suggest that SARS-CoV-2 is an obligate neuropathogen. WHERE NEXT?: The prevalence of CNS and olfactory bulb pathosis in patients with COVID-19 is not known. We postulate that, in people who have recovered from COVID-19, a chronic, recrudescent, or permanent olfactory deficit could be prognostic for an increased likelihood of neurological sequelae or neurodegenerative disorders in the long term. An inflammatory stimulus from the nasal olfactory epithelium to the olfactory bulbs and connected brain regions might accelerate pathological processes and symptomatic progression of neurodegenerative disease. Persistent olfactory impairment with or without perceptual distortions (ie, parosmias or phantosmias) after SARS-CoV-2 infection could, therefore, serve as a marker to identify people with an increased long-term risk of neurological disease.
Topics: Brain; COVID-19; Humans; Neurodegenerative Diseases; Olfaction Disorders; Olfactory Mucosa; Prospective Studies; Smell
PubMed: 34339626
DOI: 10.1016/S1474-4422(21)00182-4 -
PloS One 2019Olfactory ensheathing cells are thought to support regeneration and remyelination of damaged axons when transplanted into spinal cord injuries. Following...
Olfactory ensheathing cells are thought to support regeneration and remyelination of damaged axons when transplanted into spinal cord injuries. Following transplantation, improved locomotion has been detected in many laboratory models and in dogs with naturally-occurring spinal cord injury; safety trials in humans have also been completed. For widespread clinical implementation, it will be necessary to derive large numbers of these cells from an accessible and, preferably, autologous, source making olfactory mucosa a good candidate. Here, we compared the yield of olfactory ensheathing cells from the olfactory mucosa using 3 different techniques: rhinotomy, frontal sinus keyhole approach and rhinoscopy. From canine clinical cases with spinal cord injury, 27 biopsies were obtained by rhinotomy, 7 by a keyhole approach and 1 with rhinoscopy. Biopsy via rhinoscopy was also tested in 13 cadavers and 7 living normal dogs. After 21 days of cell culture, the proportions and populations of p75-positive (presumed to be olfactory ensheathing) cells obtained by the keyhole approach and rhinoscopy were similar (~4.5 x 106 p75-positive cells; ~70% of the total cell population), but fewer were obtained by frontal sinus rhinotomy. Cerebrospinal fluid rhinorrhea was observed in one dog and emphysema in 3 dogs following rhinotomy. Blepharitis occurred in one dog after the keyhole approach. All three biopsy methods appear to be safe for harvesting a suitable number of olfactory ensheathing cells from the olfactory mucosa for transplantation within the spinal cord but each technique has specific advantages and drawbacks.
Topics: Animals; Cell Transplantation; Cells, Cultured; Dogs; Locomotion; Nerve Regeneration; Olfactory Mucosa; Recovery of Function; Spinal Cord Injuries
PubMed: 30840687
DOI: 10.1371/journal.pone.0213252 -
The Journal of Comparative Neurology Aug 2022Olfactory epithelium (OE) is capable of lifelong regeneration due to presence of basal progenitor cells that respond to injury or neuronal loss with increased activity....
Olfactory epithelium (OE) is capable of lifelong regeneration due to presence of basal progenitor cells that respond to injury or neuronal loss with increased activity. However, this capability diminishes with advancing age and a decrease in odor perception in older individuals is well established. To characterize changes associated with age in the peripheral olfactory system, an in-depth analysis of the OE and its neuronal projections onto the olfactory bulb (OB) as a function of age was performed. Human olfactory tissue autopsy samples from 36 subjects with an average age of 74.1 years were analyzed. Established cell type-specific antibodies were used to identify OE component cells in whole mucosal sheets and epithelial sections as well as glomeruli and periglomerular structures in OB sections. With age, a reduction in OE area occurs across the mucosa progressing in a posterior-dorsal direction. Deterioration of the olfactory system is accompanied with diminution of neuron-containing OE, mature olfactory sensory neurons (OSNs) and OB innervation. On an individual level, the neuronal density within the epithelium appears to predict synapse density within the OB. The innervation of the OB is uneven with higher density at the ventral half that decreases with age as opposed to stable innervation at the dorsal half. Respiratory metaplasia, submucosal cysts, and neuromata, were commonly identified in aged OE. The finding of respiratory metaplasia and aneuronal epithelium with reduction in global basal cells suggests a progression of stem cell quiescence as an underlying pathophysiology of age-related smell loss in humans. KEY POINTS: A gradual loss of olfactory sensory neurons with age in human olfactory epithelium is also reflected in a reduction in glomeruli within the olfactory bulb. This gradual loss of neurons and synaptic connections with age occurs in a specific, spatially inhomogeneous manner. Decreasing mitotically active olfactory epithelium basal cells may contribute to age-related neuronal decline and smell loss in humans.
Topics: Aged; Anosmia; Humans; Metaplasia; Olfactory Bulb; Olfactory Mucosa; Olfactory Receptor Neurons
PubMed: 35397118
DOI: 10.1002/cne.25325 -
Current Allergy and Asthma Reports Feb 2023While the predominant cause for morbidity and mortality with SARS-CoV-2 infection is the lower respiratory tract manifestations of the disease, the effects of SARS-CoV-2... (Review)
Review
PURPOSE OF REVIEW
While the predominant cause for morbidity and mortality with SARS-CoV-2 infection is the lower respiratory tract manifestations of the disease, the effects of SARS-CoV-2 infection on the sinonasal tract have also come to the forefront especially with the increased recognition of olfactory symptom. This review presents a comprehensive summary of the mechanisms of action of the SARS-CoV-2 virus, sinonasal pathophysiology of COVID-19, and the correlation with the clinical and epidemiological impact on olfactory dysfunction.
RECENT FINDINGS
ACE2 and TMPRSS2 receptors are key players in the mechanism of infection of SARS-CoV-2. They are present within both the nasal respiratory as well as olfactory epithelia. There are however differences in susceptibility between different groups of individuals, as well as between the different SARS-CoV-2 variants. The sinonasal cavity is an important route for SARS-CoV-2 infection. While the mechanism of infection of SARS-CoV-2 in nasal respiratory and olfactory epithelia is similar, there exist small but significant differences in the susceptibility of these epithelia and consequently clinical manifestations of the disease. Understanding the differences and nuances in sinonasal pathophysiology in COVID-19 would allow the clinician to predict and counsel patients suffering from COVID-19. Future research into molecular pathways and cytokine responses at different stages of infection and different variants of SARS-CoV-2 would evaluate the individual clinical phenotype, prognosis, and possibly response to vaccines and therapeutics.
Topics: Humans; COVID-19; SARS-CoV-2; Olfactory Mucosa; Smell
PubMed: 36598732
DOI: 10.1007/s11882-022-01059-6