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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 -
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 -
Journal of Comparative Physiology. A,... May 2020Recent years have seen an explosion of interest in the evolution of neural circuits. Comparison of animals from different families, orders, and phyla reveals fascinating... (Review)
Review
Recent years have seen an explosion of interest in the evolution of neural circuits. Comparison of animals from different families, orders, and phyla reveals fascinating variation in brain morphology, circuit structure, and neural cell types. However, it can be difficult to connect the complex changes that occur across long evolutionary distances to behavior. Luckily, these changes accumulate through processes that should also be observable in recent time, making more tractable comparisons of closely related species relevant and complementary. Here, we review several decades of research on the evolution of insect olfactory circuits across short evolutionary time scales. We describe two well-studied systems, Drosophila sechellia flies and Heliothis moths, in detailed case studies. We then move through key types of circuit evolution, cataloging examples from other insects and looking for general patterns. The literature is dominated by changes in sensory neuron number and tuning at the periphery-often enhancing neural response to odorants with new ecological or social relevance. However, changes in the way olfactory information is processed by central circuits is clearly important in a few cases, and we suspect the development of genetic tools in non-model species will reveal a broad role for central circuit evolution. Moving forward, such tools should also be used to rigorously test causal links between brain evolution and behavior.
Topics: Animals; Behavior, Animal; Biological Evolution; Brain; Drosophila; Evolution, Molecular; Moths; Neural Pathways; Odorants; Olfactory Perception; Olfactory Receptor Neurons; Smell; Species Specificity
PubMed: 31984441
DOI: 10.1007/s00359-020-01399-6 -
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 -
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 -
ELife Apr 2022olfactory neurons have long been thought to express only one chemosensory receptor gene family. There are two main olfactory receptor gene families in , the odorant...
olfactory neurons have long been thought to express only one chemosensory receptor gene family. There are two main olfactory receptor gene families in , the odorant receptors (ORs) and the ionotropic receptors (IRs). The dozens of odorant-binding receptors in each family require at least one co-receptor gene in order to function: for ORs, and , , and for IRs. Using a new genetic knock-in strategy, we targeted the four co-receptors representing the main chemosensory families in (). Co-receptor knock-in expression patterns were verified as accurate representations of endogenous expression. We find extensive overlap in expression among the different co-receptors. As defined by innervation into antennal lobe glomeruli, is broadly expressed in 88% of all olfactory sensory neuron classes and is co-expressed in 82% of Orco+ neuron classes, including all neuron classes in the maxillary palp. , , and expression patterns are also more expansive than previously assumed. Single sensillum recordings from Orco-expressing mutant antennal and palpal neurons identify changes in olfactory responses. We also find co-expression of and in and olfactory neurons. These results suggest that co-expression of chemosensory receptors is common in insect olfactory neurons. Together, our data present the first comprehensive map of chemosensory co-receptor expression and reveal their unexpected widespread co-expression in the fly olfactory system.
Topics: Animals; Chemoreceptor Cells; Drosophila melanogaster; Olfactory Receptor Neurons; Receptors, Odorant; Smell
PubMed: 35442190
DOI: 10.7554/eLife.72599 -
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