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Brain Sciences Feb 2023Understanding the transmission pathways of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will aid in developing effective therapies directed at the... (Review)
Review
Understanding the transmission pathways of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will aid in developing effective therapies directed at the virus's life cycle or its side effects. While severe respiratory distress is the most common symptom of a coronavirus 2019 (COVID-19) infection, the virus is also known to cause damage to almost every major organ and system in the body. However, it is not obvious whether pathological changes in extra-respiratory organs are caused by direct infection, indirect, or combination of these effects. In this narrative review, we first elaborate on the characteristics of SARS-CoV-2, followed by the mechanisms of this virus on various organs such as brain, eye, and olfactory nerve and different systems such as the endocrine and gastrointestinal systems.
PubMed: 36979225
DOI: 10.3390/brainsci13030415 -
Chemical Senses Jan 2023The presence of a perceptual bias due to anxiety is well demonstrated in cognitive and sensory task for the visual and auditory modality. Event-related potentials, by...
The presence of a perceptual bias due to anxiety is well demonstrated in cognitive and sensory task for the visual and auditory modality. Event-related potentials, by their specific measurement of neural processes, have strongly contributed to this evidence. There is still no consensus as to whether such a bias exists in the chemical senses; chemosensory event-related potentials (CSERPs) are an excellent tool to clarify the heterogeneous results, especially since the Late Positive Component (LPC) may be an indicator of emotional involvement after chemosensory stimulation. This research examined the association between state and trait anxiety and the amplitude and latency of pure olfactory and mixed olfactory-trigeminal LPC. In this study, 20 healthy participants (11 women) with a mean age of 24.6 years (SD = 2.6) completed a validated questionnaire to measure anxiety (STAI), and CSERP was recorded during 40 pure olfactory stimulations (phenyl ethanol) and 40 mixed olfactory-trigeminal stimulations (eucalyptol). LPC latency and amplitude were measured at Cz (electrode located at midline central) for each participant. We observed a significant negative correlation between LPC latencies and the state anxiety scores for the mixed olfactory-trigeminal condition (r(18) = -0.513; P = 0.021), but not for the pure olfactory condition. We did not observe any effect on LPC amplitudes. This study suggests that a higher level of state anxiety is related to a more rapid perceptual electrophysiological response for mixed olfactory-trigeminal stimuli but not for pure odors.
Topics: Adult; Female; Humans; Young Adult; Anxiety; Evoked Potentials; Odorants; Phenylethyl Alcohol; Smell; Trigeminal Nerve; Male
PubMed: 36976248
DOI: 10.1093/chemse/bjad010 -
Journal of Nanobiotechnology Mar 2023Although exosome therapy has been recognized as a promising strategy in the treatment of rheumatoid arthritis (RA), sustained modulation on RA specific pathogenesis and...
Although exosome therapy has been recognized as a promising strategy in the treatment of rheumatoid arthritis (RA), sustained modulation on RA specific pathogenesis and desirable protective effects for attenuating joint destruction still remain challenges. Here, silk fibroin hydrogel encapsulated with olfactory ecto-mesenchymal stem cell-derived exosomes (Exos@SFMA) was photo-crosslinked in situ to yield long-lasting therapeutic effect on modulating the immune microenvironment in RA. This in situ hydrogel system exhibited flexible mechanical properties and excellent biocompatibility for protecting tissue surfaces in joint. Moreover, the promising PD-L1 expression was identified on the exosomes, which potently suppressed Tfh cell polarization via inhibiting the PI3K/AKT pathway. Importantly, Exos@SFMA effectively relieved synovial inflammation and joint destruction by significantly reducing T follicular helper (Tfh) cell response and further suppressing the differentiation of germinal center (GC) B cells into plasma cells. Taken together, this exosome enhanced silk fibroin hydrogel provides an effective strategy for the treatment of RA and other autoimmune diseases.
Topics: Humans; Hydrogels; Fibroins; Phosphatidylinositol 3-Kinases; T-Lymphocytes, Helper-Inducer; Arthritis, Rheumatoid
PubMed: 36973764
DOI: 10.1186/s12951-023-01865-8 -
Frontiers in Neuroscience 2023Prior attempts at forming theoretical predictions regarding the quality of binary odor mixtures have failed to find any consistent predictor for overshadowing of one...
Prior attempts at forming theoretical predictions regarding the quality of binary odor mixtures have failed to find any consistent predictor for overshadowing of one component in a binary mixture by the other. We test here the hypothesis that trigeminality contributes to overshadowing effects in binary mixture perception. Most odorants stimulate the trigeminal nerve in the nasal sensory epithelium. In the current study we test rats' ability to detect component odorants in four binary odor sets chosen for their relative trigeminality. We predicted that the difference in trigeminal intensity would predict the degree of overshadowing by boosting or suppressing perceptual intensity of these odorants during learning or during mixture perception. We used a two-alternative choice (TAC) task in which rats were trained to recognize the two components of each mixture and tested on a range of mixtures of the two without reinforcement. We found that even though odorant concentrations were adjusted to balance volatility, all odor sets produced asymmetric psychometric curves. Odor pairs with the greatest difference in trigeminality showed overshadowing by the odorant with weaker trigeminal properties. Odor sets with more evenly matched trigeminal properties also showed asymmetry that was not predicted by either small differences in volatility or trigeminality. Thus, trigeminal properties may influence overshadowing in odor mixtures, but other factors are also likely involved. These mixed results further support the need to test each odor mixture to determine its odor quality and underscore recent results at the level of olfactory receptor neurons that show massive and unpredictable inhibition among odorants in complex mixtures.
PubMed: 36960175
DOI: 10.3389/fnins.2023.1059741 -
Taiwan Journal of Ophthalmology 2024We aimed to compare retinal nerve fiber layer (RNFL) thickness and peripapillary vessel density values between COVID-19 patients with or without olfactory/gustatory...
PURPOSE
We aimed to compare retinal nerve fiber layer (RNFL) thickness and peripapillary vessel density values between COVID-19 patients with or without olfactory/gustatory dysfunction symptoms and healthy controls.
MATERIALS AND METHODS
We evaluated RNFL and radial peripapillary capillary vessel density (RPC-VD) values of 41 patients who had COVID-19 history and age- and gender-matched control group including 31 healthy individuals with optical coherence tomography angiography. First, post-COVID-19 group's and control group's RNFL and RPC-VD values were compared, then post-COVID-19 patients were divided into subgroups according to the presence (subgroup-A) and absence (subgroup-B) of olfactory/gustatory dysfunction symptoms, and same parameters were analyzed for subgroups.
RESULTS
Forty-one eyes of 41 post-COVID-19 patients and 31 eyes of 31 age- and gender-matched healthy controls were included in this cross-sectional study. In RNFL analysis, inferior sector thickness was found significantly lower in post-COVID-19 patients by comparison with control group ( = 0.041). In subgroup analyses, COVID-19 patients who first presented with olfactory/gustatory dysfunction symptoms had higher peripapillary and whole image optic disc capillary density ( = 0.011 and = 0.002) compared to those who had not had these symptoms.
CONCLUSION
Lower RPC-VD and RNFL thickness were detected in COVID-19 patients compared to healthy controls. Higher Disc-VD values were found in COVID-19 patients with chemosensorial dysfunction (CSD) symptoms compared to those who had not had these symptoms probably due to milder disease course in COVID-19 with CSD. Sectorial RNFL attenuation in COVID-19 might have occurred secondary to peripapillary capillary circulation defect.
PubMed: 38654983
DOI: 10.4103/tjo.TJO-D-22-00065 -
ENeuro Apr 2023The nasal epithelium houses a population of solitary chemosensory cells (SCCs). SCCs express bitter taste receptors and taste transduction signaling components and are...
The nasal epithelium houses a population of solitary chemosensory cells (SCCs). SCCs express bitter taste receptors and taste transduction signaling components and are innervated by peptidergic trigeminal polymodal nociceptive nerve fibers. Thus, nasal SCCs respond to bitter compounds, including bacterial metabolites, and these reactions evoke protective respiratory reflexes and innate immune and inflammatory responses. We tested whether SCCs are implicated in aversive behavior to specific inhaled nebulized irritants using a custom-built dual-chamber forced-choice device. The behavior of mice was recorded and analyzed for the time spent in each chamber. Wild-type (WT) mice exhibited an aversion to 10 mm denatonium benzoate (Den) or cycloheximide and spent more time in the control (saline) chamber. The SCC-pathway knock-out (KO) mice did not exhibit such an aversion response. The bitter avoidance behavior of WT mice was positively correlated with the concentration increase of Den and the number of exposures. Bitter-ageusic P2X2/3 double KO mice similarly showed an avoidance response to nebulized Den, excluding the taste system's involvement and pointing to an SCC-mediated major contributor to the aversive response. Interestingly, SCC-pathway KO mice showed an attraction to higher Den concentrations; however, chemical ablation of the olfactory epithelium eliminated this attraction attributed to the smell of Den. These results demonstrate that activation of SCCs leads to a rapid aversive response to certain classes of irritants with olfaction, but not gustation, contributing to the avoidance behavior during subsequent irritant exposures. This SCC-mediated avoidance behavior represents an important defense mechanism against the inhalation of noxious chemicals.
Topics: Mice; Animals; Irritants; Avoidance Learning; Chemoreceptor Cells; TRPM Cation Channels; Signal Transduction
PubMed: 36941059
DOI: 10.1523/ENEURO.0245-22.2023 -
Cells Feb 2023In this study, we aimed to determine whether nasally administered murine adipose-derived stem cells (ADSCs) could support olfactory regeneration in vivo. Olfactory...
In this study, we aimed to determine whether nasally administered murine adipose-derived stem cells (ADSCs) could support olfactory regeneration in vivo. Olfactory epithelium damage was induced in 8-week-old C57BL/6J male mice by intraperitoneal injection of methimazole. Seven days later, OriCell adipose-derived mesenchymal stem cells obtained from green fluorescent protein (GFP) transgenic C57BL/6 mice were nasally administered to the left nostril of these mice, and their innate odor aversion behavior to butyric acid was assessed. Mice showed significant recovery of odor aversion behavior, along with improved olfactory marker protein (OMP) expression on both sides of the upper-middle part of the nasal septal epithelium assessed by immunohistochemical staining 14 d after the treatment with ADSCs compared with vehicle control animals. Nerve growth factor (NGF) was detected in the ADSC culture supernatant, NGF was increased in the nasal epithelium of mice, and GFP-positive cells were observed on the surface of the left side nasal epithelium 24 h after left side nasal administration of ADSCs. The results of this study suggest that the regeneration of olfactory epithelium can be stimulated by nasally administered ADSCs secreting neurotrophic factors, thereby promoting the recovery of odor aversion behavior in vivo.
Topics: Mice; Male; Animals; Nerve Growth Factor; Mice, Inbred C57BL; Adipocytes; Olfactory Mucosa; Mesenchymal Stem Cells
PubMed: 36899901
DOI: 10.3390/cells12050765 -
Laboratory Investigation; a Journal of... Apr 2023Olfactory disorders, which are closely related to cognitive deterioration, can be caused by several factors, including infections, such as COVID-19; aging; and...
Olfactory disorders, which are closely related to cognitive deterioration, can be caused by several factors, including infections, such as COVID-19; aging; and environmental chemicals. Injured olfactory receptor neurons (ORNs) regenerate after birth, but it is unclear which receptors and sensors are involved in ORN regeneration. Recently, there has been great focus on the involvement of transient receptor potential vanilloid (TRPV) channels, which are nociceptors expressed on sensory nerves during the healing of damaged tissues. The localization of TRPV in the olfactory nervous system has been reported in the past, but its function there are unclear. Here, we investigated how TRPV1 and TRPV4 channels are involved in ORN regeneration. TRPV1 knockout (KO), TRPV4 KO, and wild-type (WT) mice were used to model methimazole-induced olfactory dysfunction. The regeneration of ORNs was evaluated using olfactory behavior, histologic examination, and measurement of growth factors. Both TRPV1 and TRPV4 were found to be expressed in the olfactory epithelium (OE). TRPV1, in particular, existed near ORN axons. TRPV4 was marginally expressed in the basal layer of the OE. The proliferation of ORN progenitor cells was reduced in TRPV1 KO mice, which delayed ORN regeneration and the improvement of olfactory behavior. Postinjury OE thickness improved faster in TRPV4 KO mice than WT mice but without acceleration of ORN maturation. The nerve growth factor and transforming growth factor ß levels in TRPV1 KO mice were similar to those in WT mice, and the transforming growth factor ß level was higher than TRPV4 KO mice. TRPV1 was involved in stimulating the proliferation of progenitor cells. TRPV4 modulated their proliferation and maturation. ORN regeneration was regulated by the interaction between TRPV1 and TRPV4. However, in this study, TRPV4 involvement was limited compared with TRPV1. To our knowledge, this is the first study to demonstrate the involvement of TRPV1 and TRPV4 in OE regeneration.
Topics: Animals; Mice; COVID-19; Mice, Knockout; Transient Receptor Potential Channels; TRPV Cation Channels; Olfactory Pathways; Smell
PubMed: 36870285
DOI: 10.1016/j.labinv.2022.100051 -
The Journal of Physiological Sciences :... Mar 2023In our previous research, we had demonstrated the crucial role of neuronal nicotinic acetylcholine receptors (nAChRs) in potentiation of the olfactory bulb blood flow...
In our previous research, we had demonstrated the crucial role of neuronal nicotinic acetylcholine receptors (nAChRs) in potentiation of the olfactory bulb blood flow response to olfactory stimulation in adult rats. The present study examined the effects of nAChR activation on the olfactory bulb blood flow response in rats aged 24-27 months. We found that, under urethane anesthesia, unilateral olfactory nerve stimulation (300 μA, 20 Hz, 5 s) increased blood flow within the ipsilateral olfactory bulb, without changes in the systemic arterial pressure. The increase in blood flow was dependent upon the current and frequency of the stimulus. Intravenous administration of nicotine (30 μg/kg) had little effect on the olfactory bulb blood flow response to nerve stimulation at either 2 Hz or 20 Hz. These results suggest a reduction in nAChR-mediated potentiation of the olfactory bulb blood flow response in aged rats.
Topics: Animals; Rats; Nicotine; Olfactory Bulb; Receptors, Nicotinic; Amides; Cholinergic Agents
PubMed: 36864389
DOI: 10.1186/s12576-022-00859-9 -
ENeuro Mar 2023The highly-conserved stomatin domain has been identified in genes throughout all classes of life. In animals, different stomatin domain-encoding genes have been...
The highly-conserved stomatin domain has been identified in genes throughout all classes of life. In animals, different stomatin domain-encoding genes have been implicated in the function of the kidney, red blood cells, and specific neuron types, although the underlying mechanisms remain unresolved. In one well-studied example of stomatin domain gene function, the gene and its mouse homolog are required for the function of mechanosensory neurons, where they modulate the activity of mechanosensory ion channels on the plasma membrane. Here, we identify an additional shared function for and in a very different sensory context, that of olfaction. In worms, we find that a subset of stomatin domain genes are expressed in olfactory neurons, but only is strongly required for olfactory behavior. acts cell-autonomously and multiple alternatively-spliced isoforms of can be substituted for each other. We generate a knock-out (KO) mouse and demonstrate that, like its worm homolog , it is required for olfactory behavior. In mice, is not required for odor detection, but is required for odor discrimination. Therefore, in addition to their shared roles in mechanosensory behavior, and also have a shared role in olfactory behavior.
Topics: Animals; Mice; Membrane Proteins; Cell Membrane; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Mice, Knockout; Nerve Tissue Proteins
PubMed: 36858824
DOI: 10.1523/ENEURO.0457-22.2023