Academic literature on the topic 'Nasal olfactory tissues'

Abstract OBJECTIVES. We reviewed the relationship between olfactory functions and Behçet’s disease (BD). MATERIAL AND METHODS. We searched Pubmed, Google, Google Scholar and Proquest Cebtral Database with the key words of “olfactory”, “functions”, “smell”, “nasal” and “Behçet’s disease”. RESULTS. Behçet’s disease influences the nasal mucosa. Nasal mucosal inclusion causes mucosal ulcers, pain, burning, nasal obstruction, epistaxis, nasal itching and dysosmia. Nasal cartilage deformity is also reported. The higher rate of comorbid chronic rhinosinusitis (CRS) in BD patients may likewise be because of the complex mechanism of the disease inclining the host tissues to bacterial infections. Olfactory functions may decrease in BD. Odor identification may be lower in patients BD. CONCLUSION. An olfactory dysfunction may be seen in patients with BD. BD patients should be evaluated for the involvement of the olfactory function and may require treatment because of a malfunction of the olfactory system that influences the quality of life. Neurological involvement associated with BD might play a more important role in causing olfactory dysfunction than mucosal involvement.

The enzymatic esterase activity of carboxylesterases is integral to the nasal toxicity of many esters used as industrial solvents or in polymer manufacture, including propylene glycol monomethyl ether acetate, dimethyl glutarate, dimethyl succinate, dimethyl adipate, and ethyl acrylate. Inhalation of these chemicals specifically damages the olfactory mucosa of rodents. We report the localization and differential distribution of a 59 KD carboxylesterase in nasal tissues of the rat by immunohistochemistry. Rabbit antiserum against the 59 KD rat liver microsomal carboxylesterase bound most prominently to the olfactory mucosa when applied to decalcified, paraffin-embedded sections of rat nasal turbinates. Within the olfactory mucosa, anti-carboxylesterase did not bind to sensory neurons, the target cell for ester-initiated toxicity; these cells apparently lack carboxylesterase. Instead, the antibody was preferentially bound by cells of Bowman's glands and sustentacular epithelial cells which are immediately adjacent to the olfactory nerve cells. In contrast, non-olfactory tissues (respiratory mucosa and squamous epithelium), which are more resistant to the toxicity of esters, had less carboxylesterase content. The distribution of immunoreactivity correlated well with the distribution of carboxylesterase catalytic activity described elsewhere. These findings help to link the metabolic fate of inhaled esters to the site-specific pathological findings that follow exposure to such chemicals.

Aquaporins (AQPs) are water-specific membrane channel proteins that regulate cellular and organismal water homeostasis. The nose, an organ with important respiratory and olfactory functions, is the first organ exposed to external stimuli. Nose-related topics such as allergic rhinitis (AR) and chronic rhinosinusitis (CRS) have been the subject of extensive research. These studies have reported that mechanisms that drive the development of multiple inflammatory diseases that occur in the nose and contribute to the process of olfactory recognition of compounds entering the nasal cavity involve the action of water channels such as AQPs. In this review, we provide a comprehensive overview of the relationship between AQPs and rhinologic conditions, focusing on the current state of knowledge and mechanisms that link AQPs and rhinologic conditions. Key conclusions include the following: (1) Various AQPs are expressed in both nasal mucosa and olfactory mucosa; (2) the expression of AQPs in these tissues is different in inflammatory diseases such as AR or CRS, as compared with that in normal tissues; (3) the expression of AQPs in CRS differs depending on the presence or absence of nasal polyps; and (4) the expression of AQPs in tissues associated with olfaction is different from that in the respiratory epithelium.

The nasal epithelium of the cystic fibrosis (CF) mouse has been used extensively in CF research because it exhibits ion transport defects similar to those of human CF airways. This tissue is composed of ∼50% olfactory (OE) and ∼50% ciliated epithelium (CE), and on the basis of previous observations, we hypothesized that a significant fraction of the bioelectric signals from murine nasal tissue may arise from OE rather than CE, while CE is the target tissue for CF gene therapy. We compared the bioelectric properties of isolated OE from the nasal cavity and CE from the nasopharynx in Ussing chamber studies. Hyperabsorption of Na+ [amiloride response; CF vs. wild type (WT)] was ∼7.5-fold greater in the OE compared with the CE. The forskolin response in native tissues did not reliably distinguish genotypes, likely due to a cyclic nucleotide-gated cation conductance in OE and a calcium-mediated Cl− conductance in CE. By potential difference assay, hyperabsorption of Na+ (CF vs. WT) and the difference in response to apical 0 Cl− buffer (CF vs. WT) were ∼2-fold greater in the nasal cavity compared with the nasopharynx. Our studies demonstrate that in the CF mouse, both the hyperabsorption of Na+ and the Cl− transport defect are of larger magnitude in the OE than in the CE. Thus, while the murine CF nasal epithelium is a valuable model for CF studies, the bioelectrics are likely dominated by the signals from the OE, and assays of the nasopharynx may be more specific for studying the ciliated epithelium.

ABSTRACT Animals that naturally acquire the prion diseases have a well-developed olfactory sense that they utilize for a variety of basic behaviors. To assess the potential for the nasal cavity to serve as a point of entry for prion diseases, a small amount of prion-infected brain homogenate was placed inferior to the nostrils of hamsters, where it was immediately sniffed into the nasal cavity. Hamsters extranasally inoculated with the HY strain of transmissible mink encephalopathy (TME) agent had an incubation period that was not significantly different from per os inoculation of the same dose of the HY TME agent. However, the efficiency of the nasal route of inoculation was determined to be 10 to 100 times greater based on endpoint dilution analysis. Immunohistochemistry on tissues from hamsters killed at 2-week intervals after inoculation was used to identify the disease-associated form of the prion protein (PrPd) to determine the route of prion neuroinvasion. Nasal mucosa-associated lymphoid tissue and submandibular lymph nodes initially accumulated PrPd as early as 4 weeks postinfection. PrPd was first identified in cervical lymph nodes at 8 weeks, in the mesenteric lymph nodes, spleen, and Peyer's patches at 14 weeks, and in the tongue 20 weeks after inoculation. Surprisingly, there was no evidence of PrPd in olfactory epithelium or olfactory nerve fascicles at any time after inoculation. Therefore, the HY TME agent did not enter the central nervous system via the olfactory nerve; instead, PrPd accumulated in elements of the cranial lymphoreticular system prior to neuroinvasion.

Background: Emerging evidence indicates that the misfolded tau protein can propagate aggregates between cells in a prion-like manner. This prion activity has been typically studied in brain extracts of patients with Alzheimer’s disease (AD), but not in the olfactory region that can be a potential biomarker in AD. Objective: To investigate the prion seeding activity of tau in nasal mucosa tissues using a cell culture model of tau propagation. Methods: Brain and nasal mucosa homogenates were added to HEK293T cells expressing three repeat or four-repeat domains of tau with the L266V, V337M (3RD*VM) and P301L and V377M mutations (4RD*LM) fused to the enhanced green fluorescence protein (EGFP) respectively. We also measured the level of phosphorylated tau (p-tau), total tau (t-tau), and p-tau/t-tau ratio and performed correlation analysis between tau prion activity and the level of tau. Results: We found that brain and nasal tissue homogenates from patients with AD significantly induced tau aggregation in HEK293T cells either expressing tau 3RD*VM-EGFP or 4RD*LM-EGFP compared with control brain and nasal tissue homogenates. The levels of p-tau and p-tau/t-tau ratio were significantly increased in the brain of patients with AD; however, no significant difference was found in nasal tissue compared with their respective control tissue homogenates. Conclusion: These results suggest that the nasal tissues contain tau seeds, similar to the brain, albeit without changes in the levels of p-tau and t-tau. Therefore, a cellular bioassay using nasal tissues would have great potential as an AD biomarker because of the usefulness of nasal tissue biopsy.

ABSTRACT Centrifugal spread of the prion agent to peripheral tissues is postulated to occur by axonal transport along nerve fibers. This study investigated the distribution of the pathological isoform of the protein (PrPSc) in the tongues and nasal cavities of hamsters following intracerebral inoculation of the HY strain of the transmissible mink encephalopathy (TME) agent. We report that PrPSc deposition was found in the lamina propria, taste buds, and stratified squamous epithelium of fungiform papillae in the tongue, as well as in skeletal muscle cells. Using laser scanning confocal microscopy, PrPSc was localized to nerve fibers in each of these structures in the tongue, neuroepithelial taste cells of the taste bud, and, possibly, epithelial cells. This PrPSc distribution was consistent with a spread of HY TME agent along both somatosensory and gustatory cranial nerves to the tongue and suggests subsequent synaptic spread to taste cells and epithelial cells via peripheral synapses. In the nasal cavity, PrPSc accumulation was found in the olfactory and vomeronasal epithelium, where its location was consistent with a distribution in cell bodies and apical dendrites of the sensory neurons. Prion spread to these sites is consistent with transport via the olfactory nerve fibers that descend from the olfactory bulb. Our data suggest that epithelial cells, neuroepithelial taste cells, or olfactory sensory neurons at chemosensory mucosal surfaces, which undergo normal turnover, infected with the prion agent could be shed and play a role in the horizontal transmission of animal prion diseases.

Previously we demonstrated the presence of phenol sulphotransferase (P-ST) in mouse nasal cytosols and identified its zonal location in mouse nasal cavity by staining with an antiserum raised against a rat liver P-ST isoenzyme, PSTg. In the present study a cDNA was isolated from a mouse olfactory cDNA library by immunological screening with the antiserum. The isolated cDNA consisted of 1347 bp with a 912 bp open reading frame encoding a 304-residue polypeptide. Both the nucleotide and deduced amino acid sequences of the cDNA were 94% identical with those of a rat liver P-ST isoenzyme, ST1C1. The expressed enzyme in Escherichia coli displayed high P-ST activity towards phenolic odorants such as eugenol and guaiacol, and it showed a high N-hydroxy-2-acetylaminofluorene sulphation activity in comparison with the rat ST1C1 enzyme. These results indicate that the olfactory P-ST encoded by the cDNA is a mouse orthologue of rat ST1C1; however, expression of the olfactory P-ST mRNA is specific for nasal tissues as revealed by reverse transcriptase-mediated PCR (RT–PCR).

Acute, subchronic, or chronic exposures to particulate matter (PM) and pollutant gases affect people in urban areas and those exposed to fires, disasters, and wars. Respiratory tract inflammation, production of mediators of inflammation capable of reaching the brain, systemic circulation of PM, and disruption of the nasal respiratory and olfactory barriers are likely in these populations. DNA damage is crucial in aging and in age-associated diseases such as Alzheimer's disease. We evaluated apurinic/apyrimidinic (AP) sites in nasal and brain genomic DNA, and explored by immunohistochemistry the expression of nuclear factor NF κB p65, inducible nitric oxide synthase (iNOS), cyclo-oxygenase 2 (COX2), metallothionein I and II, apolipoprotein E, amyloid precursor protein (APP), and beta-amyloid1-42 in healthy dogs naturally exposed to urban pollution in Mexico City. Nickel (Ni) and vanadium (V) were measured by inductively coupled plasma mass spectrometry (ICP-MS). Forty mongrel dogs, ages 7 days—10 years were studied (14 controls from Tlaxcala and 26 exposed to urban pollution in South West Metropolitan Mexico City (SWMMC)). Nasal respiratory and olfactory epithelium were found to be early pollutant targets. Olfactory bulb and hippocampal AP sites were significantly higher in exposed than in control age matched animals. Ni and V were present in a gradient from olfactory mucosa > olfactory bulb > frontal cortex. Exposed dogs had (a) nuclear neuronal NF κB p65, (b) endothelial, glial and neuronal iNOS, (c) endothelial and glial COX2, (d) ApoE in neuronal, glial and vascular cells, and (e) APP and β amyloid1-42 in neurons, diffuse plaques (the earliest at age 11 months), and in subarachnoid blood vessels. Increased AP sites and the inflammatory and stress protein brain responses were early and significant in dogs exposed to urban pollution. Oil combustion PM-associated metals Ni and V were detected in the brain. There was an acceleration of Alzheimer's-type pathology in dogs chronically exposed to air pollutants. Respiratory tract inflammation and deteriorating olfactory and respiratory barriers may play a role in the observed neuropathology. These data suggest that Alzheimer's disease may be the sequela of air pollutant exposures and the resulting systemic inflammation.

Background The most frequent causes of upper respiratory infections are human rhinoviruses. The nasopharyngeal area, which includes the respiratory epithelium, mucosa, and the olfactory neuroepithelium (ONe), is a first-line of defense against airborne viruses and allergens, some of which manage to penetrate the nasal mucosa and invade the tissues of the nasal respiratory epithelium. Biochemical evidence from several studies suggests that zinc is an effective cold treatment and that over-the-counter (OTC) zinc-gluconate compounds may provide the high pharmacologic doses of zinc needed to act as an effective means of treating and reducing the duration and severity of symptoms of the common cold. Methods A series of male Sprague-Dawley rats were fed an oral preparation of zinc-gluconate trihydrate or received the equivalent through drinking water to investigate the potential cytotoxic and/or neurotoxic insult to the olfactory receptor cells and other tissue in the ONe and afferent neuronal pathways. Results Coronal sections of the rat ONe and corresponding olfactory bulbs showed consistent cellular and tissue damage of increasing severity that correlated with the duration of treatment with the zinc compound when compared with the control group animals. Conclusion The results of this analysis indicate that the repeated oral administration of such zinc-containing compounds have neurotoxic effects on the ONe and to the mitral cells in the olfactory bulbs of treated rats. These findings point toward the need for increased investigation into the potential deleterious effects of zinc-containing compounds to humans as well.

Transplants of olfactory ensheathing cells (OECs) from olfactory bulbs have recently been shown to support regrowth and reinnervation of damaged spinal cord, which has led to improved functional recovery. Using complete transection in adult rat, the studies presented in this thesis examine the role of peripherally derived olfactory tissue in promoting axonal regeneration and functional recovery. Chapter One and Two provide the background to the area of spinal cord regeneration and the methods used in this thesis. Chapter Three shows that transplants of OECs from rat olfactory lamina propria (OLP) are able to support axon regrowth in the lesioned spinal cord. The BBB score was significantly higher in experimental rats (5.4???0.84) compared with control animals (1.9???0.33) (P<0.001). These dissociated OECs from OLP can promote axonal regrowth through the lesion. Histological assessment showed that: 1) axons labelled with Fluororuby grew into the injury site in OECs-transplanted rats, with occasional fibres extending into the rostral cord; 2) brainstem neurons in the raphe nucleus were retrogradely labeled with Fluororuby; and 3) serotonergic axons were detectable distal to the lesion in OECs-transplanted rats. No fibres grew into the injured region and no retrograde labeling or serotonergic fibres were seen in control animals. The role of regenerated serotonergic fibres in OECs-transplanted rats is discussed. Chapter Four demonstrates that solid pieces of OLP dissected from the nose can re-establish the continuity of the transected cord and supply the OECs that can migrate to the cord stumps to support the axon regeneration. Experimental rats which received OLP from olfactory mucosa showed significantly greater locomotive recovery (BBB scores: OLP, 5.0???1.9; control, 1.5???0.5, p<0.0001). In animals with OLP transplants, histological analysis indicated that nerve fibres, expressing neurofilament and serotonin were present at the transection site. Locomotive recovery of the hindlimbs occurred, similar to that seen after OECs transplantation. Retrograde labeling of medullary raphe neurons and gigantocellular reticular nucleus occurred following Fluororuby injection in the cord distal to the lesion, further supporting the supraspinal origin of the 5-HT innervation in the present studies. These results indicate that OLP is effective in promoting partial spinal cord repair. Chapter Five examines functional recovery of spinal reflex circuitry, ie., H-reflex excitability using paired stimuli, in OLP-transplanted rats compared with normal and respiratory lamina propria (RLP) transplanted animals. H-reflex amplitude of the conditioned response was significantly reduced in OLP transplanted rats compared to RLP transplanted animals (p< 0.05). Therefore, hindlimb reflex excitability can be modulated by OLP transplants after transection of the spinal cord in adult rats. Chapter Six examines whether functional recovery can occur if transplantation of OLP tissue is delayed by 1 month after the spinal cord transection. The BBB score was significantly higher in experimental rats (4.3???0.8 for OLP) compared with control animals (1.0???0.3, P< 0.001), but recovery was less than after acute transplantation. Asx before, histological assessment of OLP animals showed: a) serotonergic axons were present in the cord below the transection site; b) brainstem raphe nuclei was retrogradely labeled; c) bisbenzimide pre-labeled cells from OLP transplants migrated in host spinal cord. These changes were not seen in control animals. These results indicate that OLP has the ability to promote axonal regeneration in chronically injured cord of adult rats. Chapter Seven compares the results from these three types of intervention. In conclusion, these studies show that peripherally derived OECs or solid pieces of OLP can promote partial spinal cord repair in acute or chronic transection injuries. Such tissue might provide a potential source for autologous grafting in human paraplegia.

The nasal passages are constantly exposed to both air- and bloodborne foreign compounds. In particular, the olfactory mucosa is demonstrated to be susceptible to a variety of drugs and chemicals. In this thesis, mechanisms involved in tissue-selective toxicity in the olfactory mucosa of rodents have been investigated using the olfactory toxicant 2,6-dichlorophenyl methylsulphone (2,6-diClPh-MeSO₂) as a model compound. Comparative studies were performed with the non-toxic 2,5-dichlorophenyl methylsulphone (2,5-diClPh-MeSO₂) and the reasons for the strikingly different toxicity were investigated.

A strong bioactivation and protein adduction of 2,6-diClPh-MeSO₂ in olfactory microsomes and S9-fractions of rodents was demonstrated. In contrast, no significant metabolic activation of 2,5-diClPh-MeSO₂ was observed and the bioactivation in the liver for both chlorinated isomers was negligible. In vitro studies with recombinant yeast cell microsomes expressing mouse cytochrome P450 2A5 (CYP2A5) demonstrated a metabolic activation of 2,6-diClPh-MeSO₂. The 2,6-diClPh-MeSO₂-induced lesions and CYP2A5 expression preferentially occurred in Bowman’s glands and sustentacular cells of the olfactory mucosa. A significant depletion of glutathione (GSH) in the olfactory mucosa was demonstrated in vivo, while no changes were observed in the liver. There was a rapid induction of the endoplasmic reticulum (ER)-specific chaperone Grp78, activation of the ER-specific caspase-12 and the downstream caspase-3 in the Bowman’s glands. Electron microscopy revealed swelling of ER and mitochondria and a lost integrity of the Bowman’s glands.

Based on these results, the proposed mechanism for 2,6-diClPh-MeSO₂-induced toxicity in the olfactory mucosa is bioactivation by CYP2A5 into a reactive intermediate causing protein adduction and GSH-depletion. This is initiating a sequence of downstream events of ER-stress, changes in ion homeostasis, ultrastructural organelle disruption and apoptotic signalling. In spite of the initial apoptotic signals, the terminal phase of apoptosis seemed to be blocked and necrotic features occurred. The predominant expression of CYP2A5 in the olfactory mucosa is proposed to play a key role for the tissue- and cell-specific toxicity induced by 2,6-diClPh-MeSO₂.