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Brain, Behavior, and Immunity Jul 2023The olfactory epithelium undergoes constant neurogenesis throughout life in mammals. Several factors including key signaling pathways and inflammatory microenvironment...
The olfactory epithelium undergoes constant neurogenesis throughout life in mammals. Several factors including key signaling pathways and inflammatory microenvironment regulate the maintenance and regeneration of the olfactory epithelium. In this study, we identify TMEM59 (also known as DCF1) as a critical regulator to the epithelial maintenance and regeneration. Single-cell RNA-Seq data show downregulation of TMEM59 in multiple epithelial cell lineages with aging. Ablation of TMEM59 leads to apparent alteration at the transcriptional level, including genes associated with olfactory transduction and inflammatory/immune response. These differentially expressed genes are key components belonging to several signaling pathways, such as NF-κB, chemokine, etc. TMEM59 deletion impairs olfactory functions, attenuates proliferation, causes loss of both mature and immature olfactory sensory neurons, and promotes infiltration of inflammatory cells, macrophages, microglia cells and neutrophils into the olfactory epithelium and lamina propria. TMEM59 deletion deteriorates regeneration of the olfactory epithelium after injury, with significant reduction in the number of proliferative cells, immature and mature sensory neurons, accompanied by the increasing number of inflammatory cells and macrophages. Anti-inflammation by dexamethasone recovers neuronal generation and olfactory functions in the TMEM59-KO animals, suggesting the correlation between TMEM59 and inflammation in regulating the epithelial maintenance. Collectively, TMEM59 regulates olfactory functions, as well as neuronal generation in the olfactory epithelium via interaction with inflammation, suggesting a potential role in therapy against olfactory dysfunction associated with inflamm-aging.
Topics: Animals; Olfactory Receptor Neurons; Olfactory Mucosa; Inflammation; Neurogenesis; NF-kappa B; Mammals
PubMed: 37061103
DOI: 10.1016/j.bbi.2023.04.005 -
Molecular Neurobiology Aug 2023The study of psychiatric and neurological diseases requires the substrate in which the disorders occur, that is, the nervous tissue. Currently, several types of human...
The study of psychiatric and neurological diseases requires the substrate in which the disorders occur, that is, the nervous tissue. Currently, several types of human bio-specimens are being used for research, including postmortem brains, cerebrospinal fluid, induced pluripotent stem (iPS) cells, and induced neuronal (iN) cells. However, these samples are far from providing a useful predictive, diagnostic, or prognostic biomarker. The olfactory epithelium is a region close to the brain that has received increased interest as a research tool for the study of brain mechanisms in complex neuropsychiatric and neurological diseases. The olfactory sensory neurons are replaced by neurogenesis throughout adult life from stem cells on the basement membrane. These stem cells are multipotent and can be propagated in neurospheres, proliferated in vitro and differentiated into multiple cell types including neurons and glia. For all these reasons, olfactory epithelium provides a unique resource for investigating neuronal molecular markers of neuropsychiatric and neurological diseases. Here, we describe the isolation and culture of human differentiated neurons and glial cells from olfactory epithelium of living subjects by an easy and non-invasive exfoliation method that may serve as a useful tool for the research in brain diseases.
Topics: Humans; Basement Membrane; Biomarkers; Cell Adhesion; Cell Culture Techniques; Cell Differentiation; Cell Proliferation; Cell Separation; Cells, Cultured; Culture Media; Flow Cytometry; Immunohistochemistry; Magnetics; Neural Stem Cells; Neurogenesis; Neuroglia; Neurons; Olfactory Mucosa; Organ Specificity
PubMed: 37118325
DOI: 10.1007/s12035-023-03363-2 -
Current Biology : CB Apr 2023New research indicates that the odor-evoked responses of human olfactory receptors can be enhanced via the non-competitive binding of an allosteric modulator. This...
New research indicates that the odor-evoked responses of human olfactory receptors can be enhanced via the non-competitive binding of an allosteric modulator. This modulatory mechanism adds an additional layer of complexity to the peripheral encoding of odors.
Topics: Humans; Olfactory Receptor Neurons; Odorants; Receptors, Odorant; Smell
PubMed: 37098335
DOI: 10.1016/j.cub.2023.03.046 -
Auris, Nasus, Larynx Apr 2022This study examined olfactory dysfunction in LATY136F knock-in mice and its pathogenic mechanism.
OBJECTIVE
This study examined olfactory dysfunction in LATY136F knock-in mice and its pathogenic mechanism.
METHODS
The olfactory function of LATY136F knock-in mice was assessed by a behavioral test using cycloheximide solution, which has been used as a mice repellant because of its peculiar smell and unpleasant taste. The tests were administered to each group of LATY136F knock-in mice and WT mice at 8, 12, 16, 20, and 24 weeks of age. After the behavioral tests to evaluate olfactory function, the mice were sacrificed for evaluations by immunohistochemistry.
RESULTS
Behavioral tests to evaluate olfactory function showed that the LATY136F knock-in mice had a statistically significant level of olfactory dysfunction (P < 0.05). Histological analysis showed that the thickness of the olfactory epithelium in these mice was thinner than that in the age-matched wild type mice. There was no IgG4-RD like lesion in the olfactory epithelium of LATY136F knock-in mice. Olfactory marker protein and growth-associated protein 43 expressions in the olfactory epithelium of the LATY136F knock-in mice were markedly lesser than those in the wild type mice (P < 0.05).
CONCLUSION
The present study demonstrated that olfactory disturbances occurred in LATY136F knock-in mice. Furthermore, the mechanism was suggested to be reduced regeneration of the olfactory epithelium.
Topics: Animals; Immunoglobulin G4-Related Disease; Mice; Olfaction Disorders; Olfactory Marker Protein; Olfactory Mucosa; Smell
PubMed: 34348847
DOI: 10.1016/j.anl.2021.07.009 -
Chemical Senses Dec 2020Olfactory sensory neurons (OSNs) are bipolar neurons, unusual because they turn over continuously and have a multiciliated dendrite. The extensive changes in gene... (Review)
Review
Olfactory sensory neurons (OSNs) are bipolar neurons, unusual because they turn over continuously and have a multiciliated dendrite. The extensive changes in gene expression accompanying OSN differentiation in mice are largely known, especially the transcriptional regulators responsible for altering gene expression, revealing much about how differentiation proceeds. Basal progenitor cells of the olfactory epithelium transition into nascent OSNs marked by Cxcr4 expression and the initial extension of basal and apical neurites. Nascent OSNs become immature OSNs within 24-48 h. Immature OSN differentiation requires about a week and at least 2 stages. Early-stage immature OSNs initiate expression of genes encoding key transcriptional regulators and structural proteins necessary for further neuritogenesis. Late-stage immature OSNs begin expressing genes encoding proteins important for energy production and neuronal homeostasis that carry over into mature OSNs. The transition to maturity depends on massive expression of one allele of one odorant receptor gene, and this results in expression of the last 8% of genes expressed by mature OSNs. Many of these genes encode proteins necessary for mature function of axons and synapses or for completing the elaboration of non-motile cilia, which began extending from the newly formed dendritic knobs of immature OSNs. The cilia from adjoining OSNs form a meshwork in the olfactory mucus and are the site of olfactory transduction. Immature OSNs also have a primary cilium, but its role is unknown, unlike the critical role in proliferation and differentiation played by the primary cilium of the olfactory epithelium's horizontal basal cell.
Topics: Animals; Axons; Cell Differentiation; Cell Line; Cilia; Gene Expression Regulation; Humans; Neurogenesis; Olfactory Mucosa; Olfactory Receptor Neurons; Receptors, CXCR4; Receptors, Odorant; Smell; Synapses
PubMed: 33075817
DOI: 10.1093/chemse/bjaa070 -
Cell and Tissue Research Jan 2021Noses are extremely sophisticated chemical detectors allowing animals to use scents to interpret and navigate their environments. Odor detection starts with the... (Review)
Review
Noses are extremely sophisticated chemical detectors allowing animals to use scents to interpret and navigate their environments. Odor detection starts with the activation of odorant receptors (ORs), expressed in mature olfactory sensory neurons (OSNs) populating the olfactory mucosa. Different odorants, or different concentrations of the same odorant, activate unique ensembles of ORs. This mechanism of combinatorial receptor coding provided a possible explanation as to why different odorants are perceived as having distinct odors. Aided by new technologies, several recent studies have found that antagonist interactions also play an important role in the formation of the combinatorial receptor code. These findings mark the start of a new era in the study of odorant-receptor interactions and add a new level of complexity to odor coding in mammals.
Topics: Animals; Mammals; Odorants; Olfactory Receptor Neurons
PubMed: 33409650
DOI: 10.1007/s00441-020-03327-1 -
Ear, Nose, & Throat Journal May 2024The pandemic has affected over 182 million coronavirus disease 2019 (COVID-19) cases worldwide. Accumulated evidence indicates that anosmia is one of the significant... (Review)
Review
OBJECTIVES
The pandemic has affected over 182 million coronavirus disease 2019 (COVID-19) cases worldwide. Accumulated evidence indicates that anosmia is one of the significant characteristics of COVID-19 with a high prevalence. However, many aspects of COVID-19-induced anosmia are still far from being fully understood. The purpose of this review is to summarize recent developments in COVID-19-induced anosmia to increase awareness of the condition.
METHODS
A literature search was carried out using the PubMed, Embase, Web of Science, and Scopus. We reviewed the latest literature on COVID-19-induced anosmia, including mechanisms of pathogenesis, olfactory testing, anosmia as predictive tool, pathological examinations, imaging findings, affected factors, co-existing diseases, treatments, prognosis, hypothesis theories, and future directions.
RESULTS
The possible pathogenesis of COVID-19-induced anosmia may involve inflammation of the olfactory clefts and damage to the olfactory epithelium or olfactory central nervous system by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The D614G spike variant may also play a role in the increased number of anosmia patients. Anosmia may also be an essential indicator of COVID-19 spread and an early indicator of the effectiveness of political decisions. The occurrence and development of COVID-19-induced anosmia may be influenced by smoking behaviors and underlying diseases such as type 2 diabetes, gastroesophageal disorders, and rhinitis. Most patients with COVID-19-induced anosmia can fully or partially recover their olfactory function for varying durations. COVID-19-induced anosmia can be treated with various approaches such as glucocorticoids and olfactory training.
CONCLUSION
Anosmia is one of the main features of COVID-19 and the underlying disease of the patient may also influence its occurrence and development. The possible pathogenesis of COVID-19-induced anosmia is very complicated, which may involve inflammation of the olfactory clefts and damage to the olfactory epithelium or olfactory central nervous system.
Topics: COVID-19; Humans; Anosmia; SARS-CoV-2; Olfactory Mucosa; Olfaction Disorders
PubMed: 34587819
DOI: 10.1177/01455613211048998 -
Cell and Tissue Research Jan 2021Anuran amphibians (frogs and toads) typically have a complex life cycle, involving aquatic larvae that metamorphose to semi-terrestrial juveniles and adults. However,... (Review)
Review
Anuran amphibians (frogs and toads) typically have a complex life cycle, involving aquatic larvae that metamorphose to semi-terrestrial juveniles and adults. However, the anuran olfactory system is best known in Xenopus laevis, an animal with secondarily aquatic adults. The larval olfactory organ contains two distinct sensory epithelia: the olfactory epithelium (OE) and vomeronasal organ (VNO). The adult organ contains three: the OE, the VNO, and a "middle cavity" epithelium (MCE), each in its own chamber. The sensory epithelia of Xenopus larvae have overlapping sensory neuron morphology (ciliated or microvillus) and olfactory receptor gene expression. The MCE of adults closely resembles the OE of larvae, and senses waterborne odorants; the adult OE is distinct and senses airborne odorants. Olfactory subsystems in other (non-pipid) anurans are diverse. Many anuran larvae show a patch of olfactory epithelium exposed in the buccal cavity (bOE), associated with a grazing feeding mode. And other anuran adults do not have a sensory MCE, but many have a distinct patch of epithelium adjacent to the OE, the recessus olfactorius (RO), which senses waterborne odorants. Olfaction plays a wide variety of roles in the life of larval and adult anurans, and some progress has been made in identifying relevant odorants, including pheromones and feeding cues. Increased knowledge of the diversity of olfactory structure, of odorant receptor expression patterns, and of factors that affect the access of odorants to sensory epithelia will enable us to better understand the adaptation of the anuran olfactory system to aquatic and terrestrial environments.
Topics: Amphibians; Animals; Olfactory Receptor Neurons
PubMed: 33247771
DOI: 10.1007/s00441-020-03330-6 -
Biomolecules Jun 2022Cell secretome has been explored as a cell-free technique with high scientific and medical interest for Regenerative Medicine. In this work, the secretome produced and...
Cell secretome has been explored as a cell-free technique with high scientific and medical interest for Regenerative Medicine. In this work, the secretome produced and collected from Olfactory Mucosa Mesenchymal Stem Cells and Olfactory Ensheating Cells was analyzed and therapeutically applied to promote peripheral nerve regeneration. The analysis of the conditioned medium revealed the production and secretion of several factors with immunomodulatory functions, capable of intervening beneficially in the phases of nerve regeneration. Subsequently, the conditioned medium was applied to sciatic nerves of rats after neurotmesis, using Reaxon as tube-guides. Over 20 weeks, the animals were subjected to periodic functional assessments, and after this period, the sciatic nerves and cranial tibial muscles were evaluated stereologically and histomorphometrically, respectively. The results obtained allowed to confirm the beneficial effects resulting from the application of this therapeutic combination. The administration of conditioned medium from Olfactory Mucosal Mesenchymal Stem Cells led to the best results in motor performance, sensory recovery, and gait patterns. Stereological and histomorphometric evaluation also revealed the ability of this therapeutic combination to promote nervous and muscular histologic reorganization during the regenerative process. The therapeutic combination discussed in this work shows promising results and should be further explored to clarify irregularities found in the outcomes and to allow establishing the use of cell secretome as a new therapeutic field applied in the treatment of peripheral nerves after injury.
Topics: Animals; Culture Media, Conditioned; Nerve Regeneration; Olfactory Mucosa; Peripheral Nerve Injuries; Rats; Sciatic Nerve; Secretome; Stromal Cells
PubMed: 35740943
DOI: 10.3390/biom12060818 -
Open Biology Dec 2020Vertebrates develop an olfactory system that detects odorants and pheromones through their interaction with specialized cell surface receptors on olfactory sensory... (Review)
Review
Vertebrates develop an olfactory system that detects odorants and pheromones through their interaction with specialized cell surface receptors on olfactory sensory neurons. During development, the olfactory system forms from the olfactory placodes, specialized areas of the anterior ectoderm that share cellular and molecular properties with placodes involved in the development of other cranial senses. The early-diverging chordate lineages amphioxus, tunicates, lampreys and hagfishes give insight into how this system evolved. Here, we review olfactory system development and cell types in these lineages alongside chemosensory receptor gene evolution, integrating these data into a description of how the vertebrate olfactory system evolved. Some olfactory system cell types predate the vertebrates, as do some of the mechanisms specifying placodes, and it is likely these two were already connected in the common ancestor of vertebrates and tunicates. In stem vertebrates, this evolved into an organ system integrating additional tissues and morphogenetic processes defining distinct olfactory and adenohypophyseal components, followed by splitting of the ancestral placode to produce the characteristic paired olfactory organs of most modern vertebrates.
Topics: Animals; Biological Evolution; Biomarkers; Gene Expression Regulation; Olfactory Bulb; Olfactory Receptor Neurons; Organogenesis; Species Specificity; Vertebrates
PubMed: 33352063
DOI: 10.1098/rsob.200330