Analysis of local mucosal immune dysregulation to guide pilot directed therapy for long-COVID olfactory loss [TCR-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE290884 | GEO | 2025/12/25
REPOSITORIES: GEO
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Project description:To further define local mechanisms impacting peripheral olfactory structures, we obtained olfactory biopsies from subjects with post-COVID olfactory loss (hyposmia) or controls for viral, single cell and T cell receptor assays. Here we identified clonally expanded T cell subsets with a pro-inflammatory profile.
2025-12-25 | GSE290883 | GEO
Project description:The pathophysiology of post-infectious and idiopathic olfactory loss is still poorly delineated. Since proteins are key players in olfaction and technical advances including LC-MS/MS mass spectrometry give us the opportunity for detailed analysis of the nasal mucus proteome we aimed to undertake a comparative analysis of the olfactory cleft mucus proteome using mucus samples of the olfactory cleft in patients with idiopathic and postinfectious olfactory disorders versus healthy controls. The study was conceived as a pilot study and included 7 patients with idiopathic hyp- and anosmia, 7 patients with postinfectious hyp- and anosmia and 7 healthy controls. In total, 1117 different proteins were detected in at least 5 patients in at least one group. No significant different overall protein concentrations in patients compared to healthy controls (0.4614 µg/µL, SD=0.26273 vs. 0.5143 µg/µL, SD=3087; p=0.689) were found. Significant correlation regarding olfactory test results (TDI score) and protein concentrations (r=0.114, p=0.623) were either found. Results of this study did not show significant differences regarding the proteomic composition of the olfactory cleft mucus between patients suffering from postinfectious and idiopathic dysosmia versus healthy controls. Thus, central olfactory processing pathways may play a role in idiopathic and postinfectious olfactory disorders.
2018-12-10 | PXD009172 | Pride
Project description:Alzheimer's disease (AD) often begins with non-cognitive symptoms such as olfactory deficits, which can predict later cognitive decline, though the mechanisms remain unclear. Pathologically, the brainstem locus coeruleus (LC), the main source of the neurotransmitter noradrenalin (NA) modulating olfactory information processing is affected ealy. Here we show early and distinct loss of noradrenergic input to the olfactory bulb (OB) coinciding with impaired olfaction in an AD mouse model, before appearance of amyloid plaques. Mechanistically, OB microglia recognize and phagocytose LC axons. Reducing phagocytosis genetically preserves LC axons and olfaction. Importantly, patients with prodromal AD display elevated TSPO-PET signals in the OB, similarly to AppNL-G-F mice. We further confirm early LC axon degeneration in post-mortem OBs in patients with early AD. Our findings reveal a mechanism linking early LC damage to hyposmia in AD, suggesting olfactory testing and neurocircuit imaging for early diagnosis and enable timely therapeutic intervention for Alzheimer's disease.
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Project description:Olfactory ensheathing cells are one of the few central nervous system regenerative cells discovered so far. It is characterized by its lifelong nerve regeneration function, and it can also release a variety of neurotrophic factors and neural adhesion molecules. It is considered to be the glial cell with the strongest myelination ability. Olfactory ensheathing cells and Schwann cells have phenotypes in common, they can promote axon regeneration(R. Doucette, 1995). Olfactory ensheathing cells have the characteristics of Schwann cells and astrocytes, but the overall performance tends to be the former, which has two unique characteristics. First, it exists not only in the peripheral nerves (Schwann cells), but also in the central nervous system (astroglia); second, the olfactory mucosa has the ability to regenerate life-long, including human olfactory ensheathing cells(J. C. Bartolomei and C. A. Greer, 2000). Regeneration is a process in which olfactory ensheathing cells participate in efficient regulation, although the specific mechanism is not yet clear. Olfactory ensheathing cells are different from astrocytes and Schwann cells, but at the same time have the characteristics of these two cells(S. C. Barnett, 2004), like Schwann cells help axon growth, but more than Schwann cells It can make axons grow long distances, that is, it has stronger migration(A. Ramon-Cueto et al., 1998); there are also astrocytes that have a nutritional effect on the survival of neurons and the growth of axons, but olfactory ensheathing cells can also wrap neurons forms myelin sheath to support the growth of nerve processes(R. Devon and R. Doucette, 1992; J. Gu et al., 2019). There are two characteristics that make olfactory ensheathing cells the best choice for the treatment of neurological diseases(S. C. Chiu et al., 2009; J. Kim et al., 2018; M. Abdel-Rahman et al., 2018). Olfactory ensheathing cells are gradually used to treat spinal cord injuries and have shown amazing effects(J. C. Bartolomei and C. A. Greer, 2000; K. J. Liu et al., 2010; R. Yao et al., 2018). Olfactory ensheathing cells that have been used in research are usually derived from the olfactory bulb(E. H. Franssen et al., 2007), but it is easier to obtain olfactory ensheathing cells from the olfactory mucosa in clinical practice(M. Ryszard et al., 2006), so the difference between the olfactory ensheathing cells from the olfactory bulb and the olfactory mucosa There are more and more studies(B. M. U. et al., 2007), and previous studies have shown that they not only have many similar functions, but also have many differences(M. W. Richter et al., 2005; L. Wang et al., 2014; K. E. Smith et al., 2020). Because olfactory ensheathing cells derived from the olfactory bulb are not easy to obtain, olfactory ensheathing cells derived from the olfactory mucosa have become the focus of attention. Although we know that olfactory ensheathing cells from two sources have nerve repair functions, it is not clear why the two different sources of olfactory ensheathing cells have different therapeutic effects. Nicolas G. once studied that the genetic difference between the two cells and found that there are many genes related to wound repair and nerve regeneration(G. Nicolas et al., 2010). We have reason to guess that olfactory ensheathing cells from these two sources will also have a large difference in protein level. Our research group wants to use the current mature transcriptome and proteomic sequencing technologies to explore the difference between olfactory ensheathing cells from the olfactory bulb and olfactory mucosa, and explain why the two sources of olfactory ensheathing cells shows different therapeutic effects, hope to provide a new theoretical basis for future clinical treatment.
2022-02-16 | PXD024046 | Pride
Project description:Mouse olfactory sensory neurons, main olfactory epithelium and main olfactory bulb
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Project description:The aim of this study was to use global gene expression profiling to define intrinsic molecular differences that distinguish olfactory ensheathing cells from mucosa (OM-OECs) from olfactory ensheathing cells from olfactory bulb (OB-OECs). 10,000 OECs from olfactory mucosa (OM) or olfactory bulb (OB) were isolated from 4 rats.
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Project description:Despite smell impairment has been considered a potential non-motor finding in ALS, the pathobiochemistry at olfactory level remains unknown. Here, we applied an olfactory quantitative proteotyping approach to analyze the magnitude of the olfactory bulb (OB) proteostatic imbalance in ALS subjects (n=12) respect to controls (n=8).
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Project description:We used transcriptional profiling to monitor gene expression of whole olfactory bulbs at daily intervals from embryonic day 11 through birth, generating a compendium of gene expression encompassing the major developmental events of this tissue.
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Project description:Olfactory sensory neurons distinguish a large variety of odor molecules and direct the information through their axons to the olfactory bulb, the first site for the processing of olfactory information in the brain. Olfaction is very important for most mammals for the maintenance of a good quality of life. Accumulating evidences endorse that olfactory sensory decline is connected with neurodegenerative disorders including schizophrenia, depression, multiple sclerosis, Huntington's, Alzheimer's and Parkinson's diseases. For several decades, neuroanatomical, volumetric, and histological approaches have been the gold standard techniques employed to characterize the olfactory bulb functionality. Diagnosis and treatment of olfactory dysfunction remain significant health care challenges to society. Novel strategies and clues that assist in the identification of biomarker and drug development for aid in the prevention and cure of neurological diseases are necessary. However, little attention has been focused specifically on the molecular composition of the olfactory bulb from the perspective of proteomics. To this end, an in-depth mapping of the olfactory bulb proteome was carried out using high resolution tandem mass spectrometry, revealing a repertoire of 7,754 proteins. A large proportion of the identified proteins were predicted to be involved in diverse biological processes including signal transduction, metabolism, transport, olfaction and protein synthesis. Pathway analysis of the identified proteins shows that, these proteins are predominantly involved in metabolic and neural processes, chromatin modeling, and synaptic vesicle transport associated with neuronal transmission. In total, our study offers valuable understandings into the molecular composition of the human olfactory bulb proteome that could possibly help neuroscience community to understand the olfactory bulb better and open avenues for intervention strategies for olfactory dysfunction in the future.
2017-08-23 | PXD005629 | Pride