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Trends in Neurosciences Jan 2023The mechanisms of olfactory dysfunction in COVID-19 are still unclear. In this review, we examine potential mechanisms that may explain why the sense of smell is lost or... (Review)
Review
The mechanisms of olfactory dysfunction in COVID-19 are still unclear. In this review, we examine potential mechanisms that may explain why the sense of smell is lost or altered. Among the current hypotheses, the most plausible is that death of infected support cells in the olfactory epithelium causes, besides altered composition of the mucus, retraction of the cilia on olfactory receptor neurons, possibly because of the lack of support cell-derived glucose in the mucus, which powers olfactory signal transduction within the cilia. This mechanism is consistent with the rapid loss of smell with COVID-19, and its rapid recovery after the regeneration of support cells. Host immune responses that cause downregulation of genes involved in olfactory signal transduction occur too late to trigger anosmia, but may contribute to the duration of the olfactory dysfunction.
Topics: Humans; COVID-19; Smell; SARS-CoV-2; Olfaction Disorders; Olfactory Mucosa
PubMed: 36470705
DOI: 10.1016/j.tins.2022.11.003 -
Neuroscience Letters Mar 2021Patients with COVID-19 often complain of smell and taste disorders (STD). STD emerge early in the course of the disease, seem to be more common in SARS-CoV-2 infection... (Review)
Review
Patients with COVID-19 often complain of smell and taste disorders (STD). STD emerge early in the course of the disease, seem to be more common in SARS-CoV-2 infection than in other upper respiratory tract infections, and could in some cases persist for long after resolution of respiratory symptoms. Current evidence suggests that STD probably result from a loss of function of olfactory sensory neurons and taste buds, mainly caused by infection, inflammation, and subsequent dysfunction of supporting non-neuronal cells in the mucosa. However, the possible occurrence of other mechanisms leading to chemosensory dysfunction has also been hypothesized, and contrasting data have been reported regarding the direct infection of sensory neurons by SARS-CoV-2. In this mini-review, we summarize the currently available literature on pathogenesis, clinical manifestations, diagnosis, and outcomes of STD in COVID-19 and discuss possible future directions of research on this topic.
Topics: COVID-19; Humans; Mouth Mucosa; Olfaction Disorders; Olfactory Mucosa; Olfactory Receptor Neurons; SARS-CoV-2; Smell; Taste; Taste Buds; Taste Disorders
PubMed: 33600902
DOI: 10.1016/j.neulet.2021.135694 -
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 Stem Cell Oct 2019Although olfactory mucosa possesses long-lived horizontal basal stem cells (HBCs) and remarkable regenerative capacity, the function of human olfactory neuroepithelium...
Although olfactory mucosa possesses long-lived horizontal basal stem cells (HBCs) and remarkable regenerative capacity, the function of human olfactory neuroepithelium is significantly impaired in chronic inflammatory rhinosinusitis. Here, we show that, while inflammation initially damages olfactory neurons and activates HBC-mediated regeneration, continued inflammation locks HBCs in an undifferentiated state. Global gene expression in mouse HBCs reveals broad upregulation of NF-κB-regulated cytokines and chemokines including CCL19, CCL20, and CXCL10, accompanied by enhancement of "stemness"-related transcription factors. Loss-of-function studies identify an NF-κB-dependent role of HBCs in amplifying inflammatory signaling, contributing to macrophage and T cell local proliferation. Chronically activated HBCs signal macrophages to maintain immune defense and prevent Treg development. In diseased human olfactory tissue, activated HBCs in a P63 undifferentiated state similarly contribute to inflammation through chemokine production. These observations establish a mechanism of chronic rhinosinusitis-associated olfactory loss, caused by a functional switch of neuroepithelial stem cells from regeneration to immune defense.
Topics: Animals; Cell Differentiation; Cell Proliferation; Cell Self Renewal; Cells, Cultured; Chronic Disease; Humans; Immunity; Inflammation; Mice; Mice, Transgenic; NF-kappa B; Neurons; Olfactory Mucosa; Regeneration; Rhinitis; Sinusitis; Stem Cells
PubMed: 31523027
DOI: 10.1016/j.stem.2019.08.011 -
Cell Nov 2021Anosmia, the loss of smell, is a common and often the sole symptom of COVID-19. The onset of the sequence of pathobiological events leading to olfactory dysfunction...
Anosmia, the loss of smell, is a common and often the sole symptom of COVID-19. The onset of the sequence of pathobiological events leading to olfactory dysfunction remains obscure. Here, we have developed a postmortem bedside surgical procedure to harvest endoscopically samples of respiratory and olfactory mucosae and whole olfactory bulbs. Our cohort of 85 cases included COVID-19 patients who died a few days after infection with SARS-CoV-2, enabling us to catch the virus while it was still replicating. We found that sustentacular cells are the major target cell type in the olfactory mucosa. We failed to find evidence for infection of olfactory sensory neurons, and the parenchyma of the olfactory bulb is spared as well. Thus, SARS-CoV-2 does not appear to be a neurotropic virus. We postulate that transient insufficient support from sustentacular cells triggers transient olfactory dysfunction in COVID-19. Olfactory sensory neurons would become affected without getting infected.
Topics: Aged; Anosmia; Autopsy; COVID-19; Endoscopy; Female; Glucuronosyltransferase; Humans; Immunohistochemistry; In Situ Hybridization; Male; Microscopy, Fluorescence; Middle Aged; Olfaction Disorders; Olfactory Bulb; Olfactory Mucosa; Olfactory Receptor Neurons; Respiratory Mucosa; Respiratory System; SARS-CoV-2; Smell
PubMed: 34798069
DOI: 10.1016/j.cell.2021.10.027 -
Science (New York, N.Y.) Nov 2020The causative agent of coronavirus disease 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For many viruses, tissue tropism is...
The causative agent of coronavirus disease 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For many viruses, tissue tropism is determined by the availability of virus receptors and entry cofactors on the surface of host cells. In this study, we found that neuropilin-1 (NRP1), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity, an effect blocked by a monoclonal blocking antibody against NRP1. A SARS-CoV-2 mutant with an altered furin cleavage site did not depend on NRP1 for infectivity. Pathological analysis of olfactory epithelium obtained from human COVID-19 autopsies revealed that SARS-CoV-2 infected NRP1-positive cells facing the nasal cavity. Our data provide insight into SARS-CoV-2 cell infectivity and define a potential target for antiviral intervention.
Topics: Angiotensin-Converting Enzyme 2; Animals; Antibodies, Monoclonal; Betacoronavirus; COVID-19; Caco-2 Cells; Coronavirus Infections; Female; HEK293 Cells; Host Microbial Interactions; Humans; Lung; Male; Metal Nanoparticles; Mice; Mice, Inbred C57BL; Mutation; Neuropilin-1; Neuropilin-2; Olfactory Mucosa; Pandemics; Peptide Fragments; Peptidyl-Dipeptidase A; Pneumonia, Viral; Protein Binding; Protein Domains; Respiratory Mucosa; SARS-CoV-2; Serine Endopeptidases; Spike Glycoprotein, Coronavirus; Virus Internalization
PubMed: 33082293
DOI: 10.1126/science.abd2985 -
Clinical and Experimental Pharmacology... Feb 2020Naegleria fowleri, a thermophilic flagellate amoeba known as a "brain-eating" amoeba, is the aetiological agent of a perilous and devastating waterborne disease known as... (Review)
Review
Naegleria fowleri, a thermophilic flagellate amoeba known as a "brain-eating" amoeba, is the aetiological agent of a perilous and devastating waterborne disease known as primary amoebic meningoencephalitis (PAM), both in humans as well as in animals. PAM is a rare but fatal disease affecting young adults all around the world, particularly in the developed world but recently reported from developing countries, with 95%-99% mortality rate. Swimmers and divers are at high risk of PAM as the warm water is the most propitious environment adapted by N. fowleri to cause this infection. Infective amoeba in the trophozoite phase enter the victim's body through the nose, crossing the cribriform plate to reach the human brain and cause severe destruction of the central nervous system (CNS). The brain damage leads to brain haemorrhage and death occurs within 3-7 days in undiagnosed cases and maltreated cases. Though the exact pathogenesis of N. fowleri is still not known, it has exhibited two primary mechanisms, contact-independent (brain damage through different proteins) and contact-dependent (brain damage through surface structures food cups), that predominantly contribute to the pathogen invading the host CNS. For the management of this life-threatening infection different treatment regimens have been applied but still the survival rate is only 5% which is ascribed to its misdiagnosis, as the PAM symptoms closely resembled bacterial meningitis. The main objectives of this review article are to compile data to explore the sources and routes of N. fowleri infection, its association in causing PAM along with its pathophysiology; latest techniques used for accurate diagnosis, management options along with challenges for Pakistan to control this drastic disorder.
Topics: Animals; Anti-Infective Agents; Brain; Central Nervous System Protozoal Infections; Disease Management; Humans; Naegleria fowleri; Olfactory Mucosa
PubMed: 31612525
DOI: 10.1111/1440-1681.13192 -
Cell and Tissue Research Jan 2021There are 3559 species of mosquitoes in the world (Harbach 2018) but, so far, only a handful of them have been a focus of olfactory neuroscience and neurobiology... (Review)
Review
There are 3559 species of mosquitoes in the world (Harbach 2018) but, so far, only a handful of them have been a focus of olfactory neuroscience and neurobiology research. Here we discuss mosquito olfactory anatomy and function and connect these to mosquito ecology. We highlight the least well-known and thus most interesting aspects of mosquito olfactory systems and discuss promising future directions. We hope this review will encourage the insect neuroscience community to work more broadly across mosquito species instead of focusing narrowly on the main disease vectors.
Topics: Animals; Mosquito Vectors; Olfactory Receptor Neurons
PubMed: 33475852
DOI: 10.1007/s00441-020-03407-2 -
Cellular & Molecular Immunology Feb 2024Numerous pathogens can infect the olfactory tract, yet the pandemic caused by SARS-CoV-2 has strongly emphasized the importance of the olfactory mucosa as an immune... (Review)
Review
Numerous pathogens can infect the olfactory tract, yet the pandemic caused by SARS-CoV-2 has strongly emphasized the importance of the olfactory mucosa as an immune barrier. Situated in the nasal passages, the olfactory mucosa is directly exposed to the environment to sense airborne odorants; however, this also means it can serve as a direct route of entry from the outside world into the brain. As a result, olfactotropic infections can have serious consequences, including dysfunction of the olfactory system, CNS invasion, dissemination to the lower respiratory tract, and transmission between individuals. Recent research has shown that a distinctive immune response is needed to protect this neuronal and mucosal tissue. A better understanding of innate, adaptive, and structural immune barriers in the olfactory mucosa is needed to develop effective therapeutics and vaccines against olfactotropic microbes such as SARS-CoV-2. Here, we summarize the ramifications of SARS-CoV-2 infection of the olfactory mucosa, review the subsequent immune response, and discuss important areas of future research for olfactory immunity to infectious disease.
Topics: Humans; SARS-CoV-2; COVID-19; Olfactory Mucosa; Brain; Immunity
PubMed: 38143247
DOI: 10.1038/s41423-023-01119-5 -
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