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Theranostics 2021Olfactory dysfunctions, including hyposmia and anosmia, affect ~100 million people around the world and the underlying causes are not fully understood. Degeneration of...
Olfactory dysfunctions, including hyposmia and anosmia, affect ~100 million people around the world and the underlying causes are not fully understood. Degeneration of olfactory sensory neurons and incapacity of globose basal cells to generate olfactory sensory neurons are found in elder people and patients with smell disorders. Thus, olfactory stem cell may function as a promising tool to replace inactivated globose basal cells and to generate sensory neurons. We established clonal expansion of cells from the murine olfactory epithelium as well as colony growth from human olfactory mucosa using Matrigel-based three-dimensional system. These colonies were characterized by immunostaining against olfactory epithelium cellular markers and by calcium imaging of responses to odors. Chemical addition was optimized to promote Lgr5 expression, colony growth and sensory neuron generation, tested by quantitative PCR and immunostaining against progenitor and neuronal markers. The differential transcriptomes in multiple signaling pathways between colonies under different base media and chemical cocktails were determined by RNA-Seq. In defined culture media, we found that VPA and CHIR99021 induced the highest Lgr5 expression level, while LY411575 resulted in the most abundant yield of OMP mature sensory neurons in murine colonies. Different base culture media with drug cocktails led to apparent morphological alteration from filled to cystic appearance, accompanied with massive transcriptional changes in multiple signaling pathways. Generation of sensory neurons in human colonies was affected through TGF-β signaling, while Lgr5 expression and cell proliferation was regulated by VPA. Our findings suggest that targeting expansion of olfactory epithelium/mucosa colonies potentially results in discovery of new source to cell replacement-based therapy against smell loss.
Topics: Alanine; Animals; Azepines; Cell Differentiation; Cell Proliferation; Female; Humans; Male; Mice; Neurogenesis; Olfactory Mucosa; Olfactory Receptor Neurons; Pyridines; Pyrimidines; Receptors, G-Protein-Coupled; Stem Cells
PubMed: 33391499
DOI: 10.7150/thno.46750 -
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 -
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 -
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 -
European Annals of Otorhinolaryngology,... Apr 2018
Topics: Adult; Female; Humans; Laryngoscopy; Olfactory Mucosa; Pheromones, Human; Sexual Behavior; Vomeronasal Organ
PubMed: 29248349
DOI: 10.1016/j.anorl.2017.10.003 -
Cell and Tissue Research Jan 2023Sex steroid hormones influence olfactory-mediated social behaviors, and it is generally hypothesized that these effects result from circulating hormones and/or... (Review)
Review
Sex steroid hormones influence olfactory-mediated social behaviors, and it is generally hypothesized that these effects result from circulating hormones and/or neurosteroids synthesized in the brain. However, it is unclear whether sex steroid hormones are synthesized in the olfactory epithelium or the olfactory bulb, and if they can modulate the activity of the olfactory sensory neurons. Here, we review important discoveries related to the metabolism of sex steroids in the mouse olfactory epithelium and olfactory bulb, along with potential areas of future research. We summarize current knowledge regarding the expression, neuroanatomical distribution, and biological activity of the steroidogenic enzymes, sex steroid receptors, and proteins that are important to the metabolism of these hormones and reflect on their potential to influence early olfactory processing. We also review evidence related to the effects of sex steroid hormones on the development and activity of olfactory sensory neurons. By better understanding how these hormones are metabolized and how they act both at the periphery and olfactory bulb level, we can better appreciate the complexity of the olfactory system and discover potential similarities and differences in early olfactory processing between sexes.
Topics: Mice; Animals; Gonadal Steroid Hormones; Hormones; Olfactory Receptor Neurons; Olfactory Mucosa; Olfactory Bulb; Proteins; Mammals
PubMed: 36401093
DOI: 10.1007/s00441-022-03707-9