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Cell and Tissue Research Jun 2021Detection and discrimination of odorants by the olfactory system plays a pivotal role in animal survival. Olfactory-based behaviors must be adapted to an ever-changing... (Review)
Review
Detection and discrimination of odorants by the olfactory system plays a pivotal role in animal survival. Olfactory-based behaviors must be adapted to an ever-changing environment. Part of these adaptations includes changes of odorant detection by olfactory sensory neurons localized in the olfactory epithelium. It is now well established that internal signals such as hormones, neurotransmitters, or paracrine signals directly affect the electric activity of olfactory neurons. Furthermore, recent data have shown that activity-dependent survival of olfactory neurons is important in the olfactory epithelium. Finally, as olfactory neurons are directly exposed to environmental toxicants and pathogens, the olfactory epithelium also interacts closely with the immune system leading to neuroimmune modulations. Here, we review how detection of odorants can be modulated in the vertebrate olfactory epithelium. We choose to focus on three cellular types of the olfactory epithelium (the olfactory sensory neuron, the sustentacular and microvillar cells) to present the diversity of modulation of the detection of odorant in the olfactory epithelium. We also present some of the growing literature on the importance of immune cells in the functioning of the olfactory epithelium, although their impact on odorant detection is only just beginning to be unravelled.
Topics: Animals; Humans; Olfactory Mucosa; Olfactory Receptor Neurons; Receptors, Odorant; Smell
PubMed: 33961125
DOI: 10.1007/s00441-021-03467-y -
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 -
Theranostics 2022Olfactory sensory neurons (OSNs) located in the olfactory epithelium (OE) detect thousands of volatile environmental odors to form the sense of smell. OSNs are generated...
Olfactory sensory neurons (OSNs) located in the olfactory epithelium (OE) detect thousands of volatile environmental odors to form the sense of smell. OSNs are generated from basal cells, which show the characteristics of progenitor/stem cells. In the mammalian OE, persistent neurogenesis occurs during lifetime, providing a unique model to study the tissue turnover and fate determination of stem cells. Immunohistochemical analysis and RNAscope in situ hybridization indicated the localization of leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) in the intact and injured OE. Lineage tracing was conducted to analyze the dynamic role of Lgr5 cells in the OE homeostasis and regeneration. We also used DTR-driven genetic depletion of Lgr5 cells and lentivirus-mediated Lgr5 downregulation to demonstrate the essential role of Lgr5 cells in the OE regeneration. We show that Lgr5 marks horizontal basal cells (HBCs) in the OE of adults but not newborns. We revisit the role of Lgr5 cells in the OE homeostasis and regeneration, and find that Lgr5 cells participate in the OE homeostasis from neonatal to one-month-old age, as well as in the OE regeneration post injury. During the OE regeneration, Lgr5 is transiently expressed in apical supporting cells, immature neurons, and mature sensory neurons. The Lgr5 cells become or generate HBCs in the regenerated OE. DTR-driven cell depletion shows that Lgr5 cells are not necessary in the adult OE homeostasis, but required in the recovery of OE from injury. Lgr5 down-regulation by lentiviral infection also demonstrates the essential role of Lgr5 expression in the OE regeneration. Our study elucidates the role of Lgr5 cells in the OE homeostasis and regeneration, potentially providing a candidate to cell-based therapy against olfactory dysfunction.
Topics: Animals; Cell Differentiation; Cell Lineage; Mammals; Neural Stem Cells; Olfactory Mucosa; Smell
PubMed: 35966594
DOI: 10.7150/thno.60636 -
Reviews in the Neurosciences Oct 2020Just before 2020 began, a novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), brought for humans a potentially fatal disease known as... (Review)
Review
Just before 2020 began, a novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), brought for humans a potentially fatal disease known as coronavirus disease 2019 (COVID-19). The world has thoroughly been affected by COVID-19, while there has been little progress towards understanding the pathogenesis of COVID-19. Patients with a severe phenotype of disease and those who died from the disease have shown hyperinflammation and were more likely to develop neurological manifestations, linking the clinical disease with neuroimmunological features. Anosmia frequently occurs early in the course of COVID-19. The prevalence of anosmia would be influenced by self-diagnosis as well as self-misdiagnosis in patients with COVID-19. Despite this, the association between anosmia and COVID-19 has been a hope for research, aiming to understand the pathogenesis of COVID-19. Studies have suggested differently probable mechanisms for the development of anosmia in COVID-19, including olfactory cleft syndrome, postviral anosmia syndrome, cytokine storm, direct damage of olfactory sensory neurons, and impairment of the olfactory perception center in the brain. Thus, the observation of anosmia would direct us to find the pathogenesis of COVID-19 in the central nervous system, and this is consistent with numerous neurological manifestations related to COVID-19. Like other neurotropic viruses, SARS-CoV-2 might be able to enter the central nervous system via the olfactory epithelium and induce innate immune responses at the site of entry. Viral replication in the nonneural olfactory cells indirectly causes damage to the olfactory receptor nerves, and as a consequence, anosmia occurs. Further studies are required to investigate the neuroimmunology of COVID-19 in relation to anosmia.
Topics: Animals; COVID-19; Coronavirus Infections; Humans; Immunity, Innate; Olfaction Disorders; Olfactory Mucosa; Olfactory Receptor Neurons; Pandemics; Pneumonia, Viral
PubMed: 32776905
DOI: 10.1515/revneuro-2020-0039 -
Developmental Biology Sep 2018The fish Astyanax mexicanus comes in two forms: the normal surface-dwelling (SF) and the blind depigmented cave-adapted (CF) morphs. Among many phenotypic differences,...
The fish Astyanax mexicanus comes in two forms: the normal surface-dwelling (SF) and the blind depigmented cave-adapted (CF) morphs. Among many phenotypic differences, cavefish show enhanced olfactory sensitivity to detect amino-acid odors and they possess large olfactory sensory organs. Here, we questioned the relationship between the size of the olfactory organ and olfactory capacities. Comparing olfactory detection abilities of CF, SF and F1 hybrids with various olfactory epithelium (OE) sizes in behavioral tests, we concluded that OE size is not the only factor involved. Other possibilities were envisaged. First, olfactory behavior was tested in SF raised in the dark or after embryonic lens ablation, which leads to eye degeneration and mimics the CF condition. Both absence of visual function and absence of visual organs improved the SF olfactory detection capacities, without affecting the size of their OE. This suggested that developmental plasticity occurs between the visual and the olfactory modalities, and can be recruited in SF after visual deprivation. Second, the development of the olfactory epithelium was compared in SF and CF in their first month of life. Proliferation, cell death, neuronal lifespan, and olfactory progenitor cell cycling properties were identical in the two morphs. By contrast, the proportions of the three main olfactory sensory neurons subtypes (ciliated, microvillous and crypt) in their OE differed. OMP-positive ciliated neurons were more represented in SF, TRPC2-positive microvillous neurons were proportionately more abundant in CF, and S100-positive crypt cells were found in equal densities in the two morphs. Thus, general proliferative properties of olfactory progenitors are identical but neurogenic properties differ and lead to variations in the neuronal composition of the OE in SF and CF. Together, these experiments suggest that there are at least two components in the evolution of cavefish olfactory skills: (1) one part of eye-dependent developmental phenotypic plasticity, which does not depend on the size of the olfactory organ, and (2) one part of developmental evolution of the OE, which may stem from embryonic specification of olfactory neurons progenitor pools.
Topics: Animals; Behavior, Animal; Cell Death; Cell Proliferation; Characiformes; Neural Stem Cells; Olfactory Mucosa; Olfactory Perception; Smell
PubMed: 29709597
DOI: 10.1016/j.ydbio.2018.04.019 -
Scientific Reports Jun 2022Olfactory mucus contributes to the specific functions of the olfactory mucosa, but the composition and source of mucus proteins have not been fully elucidated. In this...
Olfactory mucus contributes to the specific functions of the olfactory mucosa, but the composition and source of mucus proteins have not been fully elucidated. In this study, we used comprehensive proteome analysis and identified lipocalin 15 (LCN15), a human-specific lipocalin family protein, as an abundant component of the olfactory mucus. Western blot analysis and enzyme-linked immunosorbent assay (ELISA) using a newly generated anti-LCN15 antibody showed that LCN15 was concentrated in olfactory mucus samples, but not in respiratory mucus samples. Immunohistochemical staining using anti-LCN15 antibody revealed that LCN15 localized to the cytokeratin 18-positive Bowman's glands of the olfactory cleft mucosa. Quantitative image analysis revealed that the area of LCN15 immunoreactivity along the olfactory cleft mucosa significantly correlated with the area of neuron-specific Protein-Gene Product 9.5 (PGP9.5) immunoreactivity, suggesting that LCN15 is produced in non-degenerated areas of the olfactory neuroepithelium. ELISA demonstrated that the concentration of LCN15 in the mucus was lower in participants with normal olfaction (≥ 50 years) and also tended to be lower in patients with idiopathic olfactory loss (≥ 50 years) than in participants with normal olfaction (< 50 years). Thus, LCN15 may serve as a biomarker for the activity of the Bowman's glands.
Topics: Biomarkers; Humans; Lipocalins; Mucus; Olfactory Mucosa; Smell
PubMed: 35750866
DOI: 10.1038/s41598-022-13464-y -
The Keio Journal of Medicine Mar 2005The olfactory ensheathing cell is a specialized glial cell that assists in growth of the axons of the olfactory sensory neurons as they are generated and regenerated... (Review)
Review
The olfactory ensheathing cell is a specialized glial cell that assists in growth of the axons of the olfactory sensory neurons as they are generated and regenerated throughout adult life. There is increasing evidence in animal models that transplantation of olfactory ensheathing cell promotes recovery after transplantation into the injured spinal cord. Olfactory ensheathing cell transplants have promoted regrowth of axons across the injury site and led to recovery of functional behaviours including climbing, walking, reaching, and breathing. Most evidence comes from olfactory ensheathing cells derived from the olfactory bulb. This is an impractical site for human biopsy compared to the easy accessibility of olfactory ensheathing cells from the olfactory mucosa in the nose. Our experiments demonstrated that nasal olfactory ensheathing cells led to functional improvement after complete spinal cord transaction in rat. After devising methods to grow human olfactory ensheathing cells from nasal biopsy we recently initiated a Phase I clinical trial of transplantation into the human paraplegic spinal cord.
Topics: Animals; Humans; Nerve Regeneration; Neuroglia; Olfactory Mucosa; Spinal Cord Injuries
PubMed: 15832075
DOI: 10.2302/kjm.54.8 -
Journal of Neurophysiology Nov 2017The spatial distribution of receptors within sensory epithelia (e.g., retina and skin) is often markedly nonuniform to gain efficiency in information capture and neural...
The spatial distribution of receptors within sensory epithelia (e.g., retina and skin) is often markedly nonuniform to gain efficiency in information capture and neural processing. By contrast, odors, unlike visual and tactile stimuli, have no obvious spatial dimension. What need then could there be for either nearest-neighbor relationships or nonuniform distributions of receptor cells in the olfactory epithelium (OE)? Adrian (Adrian ED. 100: 459-473, 1942; Adrian ED. 6: 330-332, 1950) provided the only widely debated answer to this question when he posited that the physical properties of odors, such as volatility and water solubility, determine a spatial pattern of stimulation across the OE that could aid odor discrimination. Unfortunately, despite its longevity, few critical tests of the "sorption hypothesis" exist. Here we test the predictions of this hypothesis by mapping mouse OE responses using the electroolfactogram (EOG) and comparing these response "maps" to computational fluid dynamics (CFD) simulations of airflow and odorant sorption patterns in the nasal cavity. CFD simulations were performed for airflow rates corresponding to quiet breathing and sniffing. Consistent with predictions of the sorption hypothesis, water-soluble odorants tended to evoke larger EOG responses in the central portion of the OE than the peripheral portion. However, sorption simulation patterns along individual nasal turbinates for particular odorants did not correlate with their EOG response gradients. Indeed, the most consistent finding was a rostral-greater to caudal-lesser response gradient for all the odorants tested that is unexplained by sorption patterns. The viability of the sorption and related olfactory "fovea" hypotheses are discussed in light of these findings. Two classical ideas concerning olfaction's receptor-surface two-dimensional organization-the sorption and olfactory fovea hypotheses-were found wanting in this study that afforded unprecedented comparisons between electrophysiological recordings in the mouse olfactory epithelium and computational fluid dynamic simulations of nasal airflow. Alternatively, it is proposed that the olfactory receptor layouts in macrosmatic mammals may be an evolutionary contingent state devoid of the functional significance found in other sensory epithelia like the cochlea and retina.
Topics: Air Movements; Analysis of Variance; Animals; Chemoreceptor Cells; Computer Simulation; Electrodiagnosis; Female; Hydrodynamics; Mice; Models, Neurological; Odorants; Olfactory Mucosa; Physical Stimulation; Respiration; Smell
PubMed: 28877965
DOI: 10.1152/jn.00455.2017 -
Seminars in Cell & Developmental Biology Jan 2013Despite studies dating back 30 or more years showing modulation of odorant responses at the level of the olfactory epithelium, most descriptions of the olfactory system... (Review)
Review
Despite studies dating back 30 or more years showing modulation of odorant responses at the level of the olfactory epithelium, most descriptions of the olfactory system infer that odorant signals make their way from detection by cilia on olfactory sensory neurons to the olfactory bulb unaltered. Recent identification of multiple subtypes of microvillar cells and identification of neuropeptide and neurotransmitter expression in the olfactory mucosa add to the growing body of literature for peripheral modulation in the sense of smell. Complex mechanisms including perireceptor events, modulation of sniff rates, and changes in the properties of sensory neurons match the sensitivity of olfactory sensory neurons to the external odorant environment, internal nutritional status, reproductive status, and levels of arousal or stress. By furthering our understanding of the players mediating peripheral olfaction, we may open the door to novel approaches for modulating the sense of smell in both health and disease.
Topics: Animals; Humans; Odorants; Olfactory Bulb; Olfactory Mucosa; Smell
PubMed: 22986099
DOI: 10.1016/j.semcdb.2012.09.001 -
International Journal of Molecular... Feb 2020Essential oils have been used in multiple ways, i.e., inhaling, topically applying on the skin, and drinking. Thus, there are three major routes of intake or application... (Review)
Review
Essential oils have been used in multiple ways, i.e., inhaling, topically applying on the skin, and drinking. Thus, there are three major routes of intake or application involved: the olfactory system, the skin, and the gastro-intestinal system. Understanding these routes is important for clarifying the mechanisms of action of essential oils. Here we summarize the three systems involved, and the effects of essential oils and their constituents at the cellular and systems level. Many factors affect the rate of uptake of each chemical constituent included in essential oils. It is important to determine how much of each constituent is included in an essential oil and to use single chemical compounds to precisely test their effects. Studies have shown synergistic influences of the constituents, which affect the mechanisms of action of the essential oil constituents. For the skin and digestive system, the chemical components of essential oils can directly activate gamma aminobutyric acid (GABA) receptors and transient receptor potential channels (TRP) channels, whereas in the olfactory system, chemical components activate olfactory receptors. Here, GABA receptors and TRP channels could play a role, mostly when the signals are transferred to the olfactory bulb and the brain.
Topics: Animals; Gastrointestinal Tract; Humans; Oils, Volatile; Olfactory Mucosa; Skin; Terpenes
PubMed: 32106479
DOI: 10.3390/ijms21051558