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Nature Neuroscience Mar 2020The presence of active neurogenic niches in adult humans is controversial. We focused attention to the human olfactory neuroepithelium, an extracranial site supplying...
The presence of active neurogenic niches in adult humans is controversial. We focused attention to the human olfactory neuroepithelium, an extracranial site supplying input to the olfactory bulbs of the brain. Using single-cell RNA sequencing analyzing 28,726 cells, we identified neural stem cell and neural progenitor cell pools and neurons. Additionally, we detailed the expression of 140 olfactory receptors. These data from the olfactory neuroepithelium niche provide evidence that neuron production may continue for decades in humans.
Topics: Adult; Aging; Humans; Neural Stem Cells; Neurogenesis; Olfactory Mucosa; Olfactory Receptor Neurons; Sequence Analysis, RNA; Single-Cell Analysis; Smell
PubMed: 32066986
DOI: 10.1038/s41593-020-0587-9 -
Cell and Tissue Research Jan 2021
Topics: Animals; Humans; Odorants; Olfactory Bulb; Olfactory Cortex; Olfactory Mucosa; Olfactory Pathways; Olfactory Perception; Receptors, Odorant; Smell
PubMed: 33447882
DOI: 10.1007/s00441-020-03389-1 -
Annual Review of Physiology 2014Mammalian pheromones control a myriad of innate social behaviors and acutely regulate hormone levels. Responses to pheromones are highly robust, reproducible, and... (Review)
Review
Mammalian pheromones control a myriad of innate social behaviors and acutely regulate hormone levels. Responses to pheromones are highly robust, reproducible, and stereotyped and likely involve developmentally predetermined neural circuits. Here, I review several facets of pheromone transduction in mammals, including (a) chemosensory receptors and signaling components of the main olfactory epithelium and vomeronasal organ involved in pheromone detection; (b) pheromone-activated neural circuits subject to sex-specific and state-dependent modulation; and (c) the striking chemical diversity of mammalian pheromones, which range from small, volatile molecules and sulfated steroids to large families of proteins. Finally, I review (d) molecular mechanisms underlying various behavioral and endocrine responses, including modulation of puberty and estrous; control of reproduction, aggression, suckling, and parental behaviors; individual recognition; and distinguishing of own species from predators, competitors, and prey. Deconstruction of pheromone transduction mechanisms provides a critical foundation for understanding how odor response pathways generate instinctive behaviors.
Topics: Animals; Behavior; Behavior, Animal; Humans; Mammals; Odorants; Olfactory Bulb; Olfactory Mucosa; Olfactory Pathways; Olfactory Receptor Neurons; Pheromones; Pheromones, Human; Smell
PubMed: 23988175
DOI: 10.1146/annurev-physiol-021113-170334 -
Proceedings of the American Thoracic... Mar 2011Olfaction represents an ancient, evolutionarily critical physiologic system. In humans, chemosensation mediates safety, nutrition, sensation of pleasure, and general... (Review)
Review
Olfaction represents an ancient, evolutionarily critical physiologic system. In humans, chemosensation mediates safety, nutrition, sensation of pleasure, and general well-being. Factors that affect human olfaction included structural aspects of the nasal cavity that can modulate airflow and therefore odorant access to the olfactory cleft, and inflammatory disease, which can affect both airflow as well as olfactory nerve function. After signals are generated, olfactory information is processed and coded in the olfactory bulb and disseminated to several areas in the brain. The discovery of olfactory receptors by Axel and Buck sparked greater understanding of the molecular basis of olfaction. However, the precise mechanisms used by this system are still under great scrutiny due to the complexity of understanding how an enormous number of chemically diverse odorant molecules are coded into signals understood by the brain. Additionally, it has been challenging to dissect olfactory sensation due to the multiple areas of areas of the brain that receive and modulate this information. Consequently, our knowledge of olfactory dysfunction in humans remains primitive. Aging represents the major cause of loss of smell, although a number of clinical and environmental factors are thought to affect chemosensory function. Treatment options focus on reducing sinonasal inflammation when present, ruling out other treatable causes, and counseling patients on safety measures.
Topics: Chemoreceptor Cells; Female; Humans; Male; Nasal Cavity; Olfaction Disorders; Olfactory Mucosa; Olfactory Receptor Neurons; Signal Transduction; Smell
PubMed: 21364221
DOI: 10.1513/pats.201005-035RN -
International Forum of Allergy &... Jun 2016Requests from researchers for olfactory mucosal biopsies are increasing as a result of advances in the fields of neuroscience and stem cell biology. Published studies...
BACKGROUND
Requests from researchers for olfactory mucosal biopsies are increasing as a result of advances in the fields of neuroscience and stem cell biology. Published studies report variable rates of success in obtaining true olfactory tissue, often below 50%. In cases where biopsies are not obtained carefully and confirmed through histological techniques, erroneous conclusions are made. Attention to the epithelium alone without submucosal analysis may add to the confusion. A consistent biopsy technique can help rhinologists obtain higher yields of olfactory mucosa. Confirmatory tissue staining analysis assures olfactory mucosa has been obtained, thereby strengthening clinical correlations and scientific conclusions.
METHODS
Biopsies of the septum within the anterior olfactory cleft were obtained under endoscopic guidance in an office procedure room using topical local anesthetic (lidocaine). After mucosal incision, a small, cupped, biopsy forceps was used to obtain specimens approximately 2 to 3 mm in size. Specimens were sectioned and analyzed with immunohistochemistry for presence of olfactory epithelium and/or olfactory fascicles.
RESULTS
A total of 14 subjects were biopsied in this analysis. Four subjects had biopsies in the operating room (OR). The remaining 10 underwent biopsies in the clinic. All biopsies obtained in the OR revealed evidence of olfactory mucosa. Of the 10 clinic biopsies, 8 (80%) revealed evidence of olfactory mucosa. No complications were encountered.
CONCLUSION
High yields of olfactory mucosa can be obtained safely in an office-based setting. Technique, including attention to the area of biopsy, and confirmatory analysis are important in assuring presence of olfactory tissue.
Topics: Adult; Aged; Ambulatory Care; Biopsy; Endoscopy; Female; Humans; Male; Middle Aged; Nerve Tissue Proteins; Neurofilament Proteins; Office Visits; Olfactory Marker Protein; Olfactory Mucosa; Receptors, Nerve Growth Factor; S100 Proteins; Tubulin; Young Adult
PubMed: 26833660
DOI: 10.1002/alr.21711 -
Translational Neurodegeneration Jul 2022In patients with Parkinson's disease (PD), real-time quaking-induced conversion (RT-QuIC) detection of pathological α-synuclein (α-syn) in olfactory mucosa (OM) is not...
BACKGROUND
In patients with Parkinson's disease (PD), real-time quaking-induced conversion (RT-QuIC) detection of pathological α-synuclein (α-syn) in olfactory mucosa (OM) is not as accurate as in other α-synucleinopathies. It is unknown whether these variable results might be related to a different distribution of pathological α-syn in OM. Thus, we investigated whether nasal swab (NS) performed in areas with a different coverage by olfactory neuroepithelium, such as agger nasi (AN) and middle turbinate (MT), might affect the detection of pathological α-syn.
METHODS
NS was performed in 66 patients with PD and 29 non-PD between September 2018 and April 2021. In 43 patients, cerebrospinal fluid (CSF) was also obtained and all samples were analyzed by RT-QuIC for α-syn.
RESULTS
In the first round, 72 OM samples were collected by NS, from AN (NS) or from MT (NS), and 35 resulted positive for α-syn RT-QuIC, including 27/32 (84%) from AN, 5/11 (45%) from MT, and 3/29 (10%) belonging to the non-PD patients. Furthermore, 23 additional PD patients underwent NS at both AN and MT, and RT-QuIC revealed α-syn positive in 18/23 (78%) NS samples and in 10/23 (44%) NS samples. Immunocytochemistry of NS preparations showed a higher representation of olfactory neural cells in NS compared to NS. We also observed α-syn and phospho-α-syn deposits in NS from PD patients but not in controls. Finally, RT-QuIC was positive in 22/24 CSF samples from PD patients (92%) and in 1/19 non-PD.
CONCLUSION
In PD patients, RT-QuIC sensitivity is significantly increased (from 45% to 84%) when NS is performed at AN, indicating that α-syn aggregates are preferentially detected in olfactory areas with higher concentration of olfactory neurons. Although RT-QuIC analysis of CSF showed a higher diagnostic accuracy compared to NS, due to the non-invasiveness, NS might be considered as an ancillary procedure for PD diagnosis.
Topics: Humans; Olfactory Mucosa; Parkinson Disease; Smell; Synucleinopathies; alpha-Synuclein
PubMed: 35902902
DOI: 10.1186/s40035-022-00311-3 -
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 -
Arquivos de Neuro-psiquiatria Apr 2016Pathology of the rhinencephalon has been a subject of interest in the fields of neurodegenerative diseases, trauma, epilepsy and other neurological conditions. Most of... (Review)
Review
Pathology of the rhinencephalon has been a subject of interest in the fields of neurodegenerative diseases, trauma, epilepsy and other neurological conditions. Most of what is known about the human rhinencephalon comes from comparative anatomy studies in other mammals and histological studies in primates. Functional imaging studies can provide new and important insight into the function of the rhinencephalon in humans but have limited spatial resolution, limiting its contribution to the study of the anatomy of the human rhinencephalon. In this study we aim to provide a brief and objective review of the anatomy of this important and often overlooked area of the nervous system.
Topics: Humans; Medical Illustration; Olfactory Bulb; Olfactory Cortex; Olfactory Mucosa; Olfactory Receptor Neurons
PubMed: 27097007
DOI: 10.1590/0004-282X20160043 -
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 -
Scientific Reports Aug 2021The nasal mucosa (NM) contains olfactory mucosa which contributes to the detection of odorant molecules and the transmission of olfactory information to the brain. To... (Clinical Trial)
Clinical Trial
The nasal mucosa (NM) contains olfactory mucosa which contributes to the detection of odorant molecules and the transmission of olfactory information to the brain. To date, the lipid composition of the human NM has not been adequately characterized. Using gas chromatography, liquid chromatography coupled to mass spectrometry and thin layer chromatography, we analyzed the fatty acids and the phospholipid and ceramide molecular species in adult human nasal and blood biopsies. Saturated and polyunsaturated fatty acids (PUFAs) accounted for 45% and 29% of the nasal total fatty acids, respectively. Fatty acids of the n-6 family were predominant in the PUFA subgroup. Linoleic acid and arachidonic acid (AA) were incorporated in the main nasal phospholipid classes. Correlation analysis revealed that the nasal AA level might be positively associated with olfactory deficiency. In addition, a strong positive association between the AA levels in the NM and in plasma cholesteryl esters suggested that this blood fraction might be used as an indicator of the nasal AA level. The most abundant species of ceramides and their glycosylated derivatives detected in NM contained palmitic acid and long-chain fatty acids. Overall, this study provides new insight into lipid species that potentially contribute to the maintenance of NM homeostasis and demonstrates that circulating biomarkers might be used to predict nasal fatty acid content.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Fatty Acids; Female; Gas Chromatography-Mass Spectrometry; Humans; Lipidomics; Male; Middle Aged; Olfaction Disorders; Olfactory Mucosa
PubMed: 34408170
DOI: 10.1038/s41598-021-93817-1