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Science Immunology Feb 2024The olfactory neuroepithelium serves as a sensory organ for odors and forms part of the nasal mucosal barrier. Olfactory sensory neurons are surrounded and supported by...
The olfactory neuroepithelium serves as a sensory organ for odors and forms part of the nasal mucosal barrier. Olfactory sensory neurons are surrounded and supported by epithelial cells. Among them, microvillous cells (MVCs) are strategically positioned at the apical surface, but their specific functions are enigmatic, and their relationship to the other specialized epithelial cells is unclear. Here, we establish that the family of MVCs comprises tuft cells and ionocytes in both mice and humans. Integrating analysis of the respiratory and olfactory epithelia, we define the distinct receptor expression of TRPM5 tuft-MVCs compared with Gɑ-gustducin respiratory tuft cells and characterize a previously undescribed population of glandular DCLK1 tuft cells. To establish how allergen sensing by tuft-MVCs might direct olfactory mucosal responses, we used an integrated single-cell transcriptional and protein analysis. Inhalation of induced mucosal epithelial effector molecules including and a distinct pathway leading to proliferation of the quiescent olfactory horizontal basal stem cell (HBC) pool, both triggered in the absence of olfactory apoptosis. and ATP-elicited HBC proliferation was dependent on TRPM5 tuft-MVCs, identifying these specialized epithelial cells as regulators of olfactory stem cell responses. Together, our data provide high-resolution characterization of nasal tuft cell heterogeneity and identify a function of TRPM5 tuft-MVCs in directing the olfactory mucosal response to allergens.
Topics: Humans; Mice; Animals; Tuft Cells; Olfactory Mucosa; Nasal Mucosa; Epithelial Cells; Cell Proliferation; Doublecortin-Like Kinases
PubMed: 38306414
DOI: 10.1126/sciimmunol.abq4341 -
Scientific Reports Jan 2024An important question in neuroscience is how sensory systems change as animals grow and interact with the environment. Exploring sensory systems in animals as they...
An important question in neuroscience is how sensory systems change as animals grow and interact with the environment. Exploring sensory systems in animals as they develop can reveal how networks of neurons process information as the neurons themselves grow and the needs of the animal change. Here we compared the structure and function of peripheral parts of the olfactory pathway in newly hatched and adult locusts. We found that populations of olfactory sensory neurons (OSNs) in hatchlings and adults responded with similar tunings to a panel of odors. The morphologies of local neurons (LNs) and projection neurons (PNs) in the antennal lobes (ALs) were very similar in both age groups, though they were smaller in hatchlings, they were proportional to overall brain size. The odor evoked responses of LNs and PNs were also very similar in both age groups, characterized by complex patterns of activity including oscillatory synchronization. Notably, in hatchlings, spontaneous and odor-evoked firing rates of PNs were lower, and LFP oscillations were lower in frequency, than in the adult. Hatchlings have smaller antennae with fewer OSNs; removing antennal segments from adults also reduced LFP oscillation frequency. Thus, consistent with earlier computational models, the developmental increase in frequency is due to increasing intensity of input to the oscillation circuitry. Overall, our results show that locusts hatch with a fully formed olfactory system that structurally and functionally matches that of the adult, despite its small size and lack of prior experience with olfactory stimuli.
Topics: Animals; Grasshoppers; Odorants; Olfactory Pathways; Olfactory Receptor Neurons; Interneurons; Smell
PubMed: 38297144
DOI: 10.1038/s41598-024-52879-7 -
STAR Protocols Mar 2024We present a protocol for the rapid postmortem bedside procurement of selected tissue samples using an endoscopic endonasal surgical technique that we adapted from skull...
We present a protocol for the rapid postmortem bedside procurement of selected tissue samples using an endoscopic endonasal surgical technique that we adapted from skull base surgery. We describe steps for the postmortem collection of blood, cerebrospinal fluid, a nasopharyngeal swab, and tissue samples; the clean-up procedure; and the initial processing and storage of the samples. This protocol was validated with tissue samples procured postmortem from COVID-19 patients and can be applied in another emerging infectious disease. For complete details on the use and execution of this protocol, please refer to Khan et al. (2021) and Khan et al. (2022)..
Topics: Humans; Plastic Surgery Procedures; Skull Base; Endoscopy; Olfactory Mucosa; Frontal Lobe
PubMed: 38277268
DOI: 10.1016/j.xpro.2023.102831 -
PLoS Biology Jan 2024In vertebrates, olfactory receptors localize on multiple cilia elaborated on dendritic knobs of olfactory sensory neurons (OSNs). Although olfactory cilia dysfunction...
In vertebrates, olfactory receptors localize on multiple cilia elaborated on dendritic knobs of olfactory sensory neurons (OSNs). Although olfactory cilia dysfunction can cause anosmia, how their differentiation is programmed at the transcriptional level has remained largely unexplored. We discovered in zebrafish and mice that Foxj1, a forkhead domain-containing transcription factor traditionally linked with motile cilia biogenesis, is expressed in OSNs and required for olfactory epithelium (OE) formation. In keeping with the immotile nature of olfactory cilia, we observed that ciliary motility genes are repressed in zebrafish, mouse, and human OSNs. Strikingly, we also found that besides ciliogenesis, Foxj1 controls the differentiation of the OSNs themselves by regulating their cell type-specific gene expression, such as that of olfactory marker protein (omp) involved in odor-evoked signal transduction. In line with this, response to bile acids, odors detected by OMP-positive OSNs, was significantly diminished in foxj1 mutant zebrafish. Taken together, our findings establish how the canonical Foxj1-mediated motile ciliogenic transcriptional program has been repurposed for the biogenesis of immotile olfactory cilia, as well as for the development of the OSNs.
Topics: Animals; Humans; Mice; Zebrafish; Cilia; Forkhead Transcription Factors; Olfactory Receptor Neurons; Olfactory Mucosa
PubMed: 38271330
DOI: 10.1371/journal.pbio.3002468 -
International Journal of Molecular... Jan 2024Demyelination in the central nervous system (CNS) resulting from injury or disease can cause loss of nerve function and paralysis. Cell therapies intended to promote...
Demyelination in the central nervous system (CNS) resulting from injury or disease can cause loss of nerve function and paralysis. Cell therapies intended to promote remyelination of axons are a promising avenue of treatment, with mesenchymal stromal cells (MSCs) a prominent candidate. We have previously demonstrated that MSCs derived from human olfactory mucosa (hOM-MSCs) promote myelination to a greater extent than bone marrow-derived MSCs (hBM-MSCs). However, hOM-MSCs were developed using methods and materials that were not good manufacturing practice (GMP)-compliant. Before considering these cells for clinical use, it is necessary to develop a method for their isolation and expansion that is readily adaptable to a GMP-compliant environment. We demonstrate here that hOM-MSCs can be derived without enzymatic tissue digestion or cell sorting and without culture antibiotics. They grow readily in GMP-compliant media and express typical MSC surface markers. They robustly produce CXCL12 (a key secretory factor in promoting myelination) and are pro-myelinating in in vitro rodent CNS cultures. GMP-compliant hOM-MSCs are comparable in this respect to those grown in non-GMP conditions. However, when assessed in an in vivo model of demyelinating disease (experimental autoimmune encephalitis, EAE), they do not significantly improve disease scores compared with controls, indicating further pre-clinical evaluation is necessary before their advancement to clinical trials.
Topics: Humans; Culture Techniques; Anti-Bacterial Agents; Axons; Biological Transport; Mesenchymal Stem Cells
PubMed: 38255817
DOI: 10.3390/ijms25020743 -
Pathogens (Basel, Switzerland) Dec 2023Tuberculosis (TB) of the central nervous system (CNS) is a lethal and incapacitating disease. Several studies have been performed to understand the mechanism of...
Tuberculosis (TB) of the central nervous system (CNS) is a lethal and incapacitating disease. Several studies have been performed to understand the mechanism of bacterial arrival to CNS, however, it remains unclear. Although the interaction of the host, the pathogen, and the environment trigger the course of the disease, in TB the characteristics of these factors seem to be more relevant in the genesis of the clinical features of each patient. We previously tested three mycobacterial clinical isolates with distinctive genotypes obtained from the cerebrospinal fluid of patients with meningeal TB and showed that these strains disseminated extensively to the brain after intratracheal inoculation and pulmonary infection in BALB/c mice. In this present study, BALB/c mice were infected through the intranasal route. One of these strains reaches the olfactory bulb at the early stage of the infection and infects the brain before the lungs, but the histological study of the nasal mucosa did not show any alteration. This observation suggests that some mycobacteria strains can arrive directly at the brain, apparently toward the olfactory nerve after infecting the nasal mucosa, and guides us to study in more detail during mycobacteria infection the nasal mucosa, the associated connective tissue, and nervous structures of the cribriform plate, which connect the nasal cavity with the olfactory bulb.
PubMed: 38251344
DOI: 10.3390/pathogens13010037 -
Journal of Neuroimmunology Feb 2024We examined the histopathological changes in the olfactory mucosa of cynomolgus and rhesus macaque models of SARS-CoV-2 infection. SARS-CoV-2 infection induced severe...
We examined the histopathological changes in the olfactory mucosa of cynomolgus and rhesus macaque models of SARS-CoV-2 infection. SARS-CoV-2 infection induced severe inflammatory changes in the olfactory mucosa. A major histocompatibility complex (MHC) class II molecule, HLA-DR was expressed in macrophage and supporting cells, and melanocytes were increased in olfactory mucosa. Supporting cells and olfactory neurons were infected, and SARS-CoV-2 N protein was detected in the axons of olfactory neurons and in olfactory bulbs. Viral RNA was detected in olfactory bulbs and brain tissues. The olfactory epithelium-olfactory bulb pathway may be important as a route for intracranial infection by SARS-CoV-2.
Topics: Animals; Olfactory Bulb; SARS-CoV-2; COVID-19; Macaca mulatta; Olfactory Mucosa; Inflammation; Macaca fascicularis
PubMed: 38237527
DOI: 10.1016/j.jneuroim.2024.578288 -
Journal of Neuroinflammation Jan 2024Venezuelan Equine Encephalitis virus (VEEV) may enter the central nervous system (CNS) within olfactory sensory neurons (OSN) that originate in the nasal cavity after...
BACKGROUND
Venezuelan Equine Encephalitis virus (VEEV) may enter the central nervous system (CNS) within olfactory sensory neurons (OSN) that originate in the nasal cavity after intranasal exposure. While it is known that VEEV has evolved several mechanisms to inhibit type I interferon (IFN) signaling within infected cells, whether this inhibits virologic control during neuroinvasion along OSN has not been studied.
METHODS
We utilized an established murine model of intranasal infection with VEEV and a repository of scRNAseq data from IFN-treated OSN to assess the cellular targets and IFN signaling responses after VEEV exposure.
RESULTS
We found that immature OSN, which express higher levels of the VEEV receptor LDLRAD3 than mature OSN, are the first cells infected by VEEV. Despite rapid VEEV neuroinvasion after intranasal exposure, olfactory neuroepithelium (ONE) and olfactory bulb (OB) IFN responses, as assessed by evaluation of expression of interferon signaling genes (ISG), are delayed for up to 48 h during VEEV neuroinvasion, representing a potential therapeutic window. Indeed, a single intranasal dose of recombinant IFNα triggers early ISG expression in both the nasal cavity and OB. When administered at the time of or early after infection, IFNα treatment delayed onset of sequelae associated with encephalitis and extended survival by several days. VEEV replication after IFN treatment was also transiently suppressed in the ONE, which inhibited subsequent invasion into the CNS.
CONCLUSIONS
Our results demonstrate a critical and promising first evaluation of intranasal IFNα for the treatment of human encephalitic alphavirus exposures.
Topics: Humans; Mice; Animals; Encephalitis Virus, Venezuelan Equine; Olfactory Receptor Neurons; Central Nervous System; Virus Replication
PubMed: 38233868
DOI: 10.1186/s12974-023-02960-1 -
Proceedings. Biological Sciences Jan 2024In the silkmoth , the role of male sensilla trichodea in pheromone detection is well established. Here we study the corresponding female sensilla, which contain two...
In the silkmoth , the role of male sensilla trichodea in pheromone detection is well established. Here we study the corresponding female sensilla, which contain two olfactory sensory neurons (OSNs) and come in two lengths, each representing a single physiological type. Only OSNs in medium trichoids respond to the scent of mulberry, the silkworm's exclusive host plant, and are more sensitive in mated females, suggesting a role in oviposition. In long trichoids, one OSN is tuned to (+)-linalool and the other to benzaldehyde and isovaleric acid, both odours emitted by silkworm faeces. While the significance of (+)-linalool detection remains unclear, isovaleric acid repels mated females and may therefore play a role in avoiding crowded oviposition sites. When we examined the underlying molecular components of neurons in female trichoids, we found non-canonical co-expression of , the co-receptor for acid responses, and , the co-receptor of odorant receptors, in long trichoids, and the unexpected expression of a specific odorant receptor in both trichoid sensillum types. In addition to elucidating the function of female trichoids, our results suggest that some accepted organizational principles of the insect olfactory system may not apply to the predominant sensilla on the antenna of female .
Topics: Animals; Female; Bombyx; Sensilla; Smell; Olfactory Receptor Neurons; Receptors, Odorant; Pheromones; Acyclic Monoterpenes; Pentanoic Acids; Hemiterpenes
PubMed: 38228178
DOI: 10.1098/rspb.2023.2578 -
American Journal of Stem Cells 2023The present study aimed to assess alterations in apoptosis rate, Golgi morphology and GOLPH3 expression following intracerebral hemorrhage (ICH) both before and after...
INTRODUCTION
The present study aimed to assess alterations in apoptosis rate, Golgi morphology and GOLPH3 expression following intracerebral hemorrhage (ICH) both before and after intervention with OM-MSCs. The objective was to investigate the impact of ICH on Golgi apparatus (GA) stress and to explore the potential protective effects of OM-MSCs on GA following ICH.
MATERIAL AND METHODS
A total of 54 Sprague-Dawley rats were allocated into three experimental groups: sham operation group, ICH group and OM-MSCs group. ICH models were established by collagenase method while OM-MSCs were cultured in vitro. In OM-MSCs intervention group, one million OM-MSCs were stereotactically injected into unilateral striatum of rats 48 hours after ICH modeling while other two groups received an equivalent volume of PBS. Brain tissues were collected at 1 day, 3 day and 7 day post intervention and subsequently assessed for cellular apoptosis, morphological change of GA and expression of GOLPH3. The obtained data were subjected to statistical analysis by SPSS 21.0.
RESULTS
1. Apoptosis rate in the 1 d and 3 d ICH groups was significantly higher compared to sham operation group (P < 0.05), but significantly lower compared to OM-MSCs intervention group (P < 0.05). 2. While no noticeable morphological changes were observed in sham operation group, GA in ICH group exhibited a significant increase fragmentation. After OM-MSCs intervention, the fragmentation of GA decreased significantly. 3. On 3 d, expression of GOLPH3 in ICH group was significantly higher than that in sham operation group (P < 0.05) but significantly lower than that of OM-MSCs intervention group (P < 0.05).
CONCLUSIONS
The rate of apoptosis, fragmentation of GA, and expression of GOLPH3 exhibited significant increases following ICH in SD rats. Conversely, all of these factors demonstrated significant decreases subsequent to early intervention with OM-MSCs, thereby exerting neuroprotective effects.
PubMed: 38213638
DOI: No ID Found