Mouse Olfactory Epithelium Research Articles

3-Methylindole-induced nasal mucosal damage in mice.

3-Methylindole (3MI) damages nasal olfactory epithelium in mice. Lesions were studied histologically from 30 minutes to 28 days after intraperitoneal injection of 400 mg 3MI/kg. Cellular swelling was apparent in olfactory epithelium by 6 hours after injection of 3MI, while respiratory epithelium was normal. Necrosis of olfactory epithelium and subepithelial glands was diffuse by 48 hours. Subsequent ulceration resulted in epithelial hyperplasia, squamous metaplasia, fibroplasia, and ossification. Partially occlusive intranasal fibrous and osseous tissue persisted through 28 days after 3MI injection.

Josamycin and troleandomycin increase hepatic glutathione turnover in rats

Naphthalene produces species and cell selective injury to respiratory tract epithelial cells of rodents. In these studies we determined the apparent Km, Vmax, and catalytic efficiency (Vmax/Km) for naphthalene metabolism in microsomal preparations from subcompartments of the respiratory tract of rodents and non-human primates. In tissues with high substrate turnover, major metabolites were derived directly from naphthalene oxide with smaller amounts from conjugates of diol epoxide, diepoxide, and 1,2- and 1,4-naphthoquinones. In some tissues, different enzymes with dissimilar Km and Vmax appeared to metabolize naphthalene. The rank order of Vmax (rat olfactory epithelium > mouse olfactory epithelium > murine airways ≫ rat airways) correlated well with tissue susceptibility to naphthalene. The Vmax in monkey alveolar subcompartment was 2% that in rat nasal olfactory epithelium. Rates of metabolism in nasal compartments of the monkey were low. The catalytic efficiencies of microsomes from known susceptible tissues/subcompartments are 10 and 250 fold higher than in rat airway and monkey alveolar subcompartments, respectively. Although the strong correlations between catalytic efficiencies and tissue susceptibility suggest that non-human primate tissues are unlikely to generate metabolites at a rate sufficient to produce cellular injury, other studies showing high levels of formation of protein adducts support the need for additional studies.

An autoradiographic study of the mouse olfactory epithelium: evidence for long-lived receptors.

In order to try to determine whether differentiated olfactory receptors turn over (die and are replaced by newly differentiated cells) during adult life, mice were injected with a single dose of 3H-thymidine at either 2 or 4 months of age and allowed to survive for up to 12 months; they were caged in a laminar flow unit to prevent rhinitis. Counts of labeled receptor cells detected autoradiographically after injection at 2 months of age revealed that, following an initial decrease from 1 to 3 months of survival, numbers of labeled cells remained approximately constant, at least up to 12 months of survival. Cells still labeled at 12 months of survival were confirmed as receptor cells by electron microscopic examination of reembedded sections. The hypothesis is suggested that in the absence of disease-related destruction of the olfactory epithelium, most or all receptor cell turnover represents newly formed cells that fail to establish synapses with the olfactory bulb; fully differentiated receptor cells may be quite long-lived.

Olfactory marker protein: turnover and transport in normal and regenerating neurons

A 19,000-dalton acidic protein designated olfactory marker protein (OMP) is a cell-specific marker of mature olfactory chemosensory neurons. Intranasal irrigation of mouse olfactory epithelium with [35S]methionine labeled OMP to high specific activity. Turnover and transport characteristics of 35S-labeled OMP were compared to those of 35S-labeled global cytosol protein in groups of young, adult, and Triton-treated adult mice. The latter contained primarily large numbers of regenerating olfactory neurons. In olfactory epithelium of young and Triton-treated mice, the specific activity of OMP was three times that of global cytosol protein, whereas in adults the two measures were equal. In all three groups, however, the rate of degradation of OMP was roughly equal to that of cytosol protein (T1/2 = 5 to 6 days). By contrast, differences in T1/2 for OMP decline in the bulb of adult, young, and Triton-treated adult mice were highly significant (T1/2's of 9.3, 6.1, and 4 to 5 days, respectively; p = 0.001). The specific activity of [35S]methionine incorporated in OMP exceeded that of the free amino acid 5-fold, indicating minimal precursor reutilization during the course of our experiments. Turnover data indicate that increased isotope incorporation into OMP in the epithelium is matched by an accelerated rate of degradation in the bulb. This may be correlated with the physiological state or developmental age of the primary neurons since in young and Triton-treated adult mice, rapidly maturing "young" olfactory neurons represent a larger proportion of the total population than in adults. Thus, OMP behaves as a typical, relatively slowly transported soluble protein (v = 2 to 4 mm/day, slow component b).

The subcellular distribution of carnosine, carnosine synthetase, and carnosinase in mouse olfactory tissues

The dipeptide, carnosine, its synthetic enzyme, carnosine synthetase, and its degradative enzyme, carnosinase, appear to be localized in the cytosol of mouse olfactory bulb and epithelium. Mouse olfactory bulbs and epithelium were prelabeled in vivo with [ 3H]carnosine following intranasal irrigation with [ 3H]β-alanine. [ 3H]-carnosine co-distributed in olfactory bulb with lactate dehydrogenase with only 10% in the crude mitochondrial fraction. Similar results were also seen with endogenous carnosine distribution. Over 70% of the carnosine present in the crude mitochondrial fraction was localized in synaptosomes following sucrose gradient centrifugation. However, further fractionation of vesicle containing fractions from osmotically lysed crude mitochondrial fractions indicated that [ 3H]carnosine was not associated with vesicles. Nearly 70% of all the [ 3H]carnosine present in olfactory epithelium was soluble with most of the remainder in the crude nuclear fraction. The enzymes carnosine synthetase and carnosinase were clearly soluble in olfactory epithelium with 98% and 85% of the activity in the cytosol. Less than 2% was found in the crude mitochondrial fraction. In olfactory bulb both enzymes also appeared soluble.

Denervation in the primary olfactory pathway of mice. II. Effects on carnosine and other amine compounds

Carnosine (β-alanyl- l-histidine) is present in the olfactory bulb and olfactory epithelium of mice and rats at 1–2 nmole/mg tissue. Peripheral deafferentation or central denervation causes a rapid, selective decrease of this dipeptide from the reciprocal portion of the primary olfactory pathway. These data demonstrate the localization of carnosine within the primary olfactory chemoreceptor neurons and suggest a possible role for this compound in neural transmission.

Electron spin resonance measurements of molecular interactions in mouse olfactory epithelium

THE mechanism by which molecules interact with, and so stimulate, the surfaces of olfactory receptor cells has given rise to much speculation. Since oil-soluble substances are often very effective odours, it has been proposed that olfactory transduction occurs when an odorant molecule perturbs the lipids of the sensory membranes. Conversely, the known steric aspects of odorant molecule interactions argue for a more specific binding for which a protein would be a more suitable receptor1–4.

Alkaline Phosphatase in Taste Buds and Nasal Mucosa

THE application of Gomori‘s (1939) technique for the demonstration of alkaline phospho-mono-esterase to various organs and tissues of the body1, 2, 3showed the enzyme to be located in many hitherto unsuspected sites. In view of its association with the absorptive part of the alimentary tract, and since the process of tasting and smelling appear to involve an absorptive process, it was considered desirable to test for phosphatase in taste buds and olfactory mucosa. Pieces of tongue of bat (Nyctalus noctula), mouse, rabbit, monkey (Cercopithecus griseus) and human being, and pieces of mouse, rabbit and human olfactory and nasal (respiratory) epithelium were therefore treated by Gomori‘s technique.