Olfactory Mucous Membrane Research Articles

Olfactory Ecto-Mesenchymal Stem Cells in Modeling and Treating Alzheimer's Disease.

Alzheimer's disease (AD) is a condition in the brain that is marked by a gradual and ongoing reduction in memory, thought, and the ability to perform simple tasks. AD has a poor prognosis but no cure yet. Therefore, the need for novel models to study its pathogenesis and therapeutic strategies is evident, as the brain poorly recovers after injury and neurodegenerative diseases and can neither replace dead neurons nor reinnervate target structures. Recently, mesenchymal stem cells (MSCs), particularly those from the human olfactory mucous membrane referred to as the olfactory ecto-MSCs (OE-MSCs), have emerged as a potential avenue to explore in modeling AD and developing therapeutics for the disease due to their lifelong regeneration potency and facile accessibility. This review provides a comprehensive summary of the current literature on isolating OE-MSCs and delves into whether they could be reliable models for studying AD pathogenesis. It also explores whether healthy individual-derived OE-MSCs could be therapeutic agents for the disease. Despite being a promising tool in modeling and developing therapies for AD, some significant issues remain, which are also discussed in the review.

Morphological features of changes in peripheral olfactory structures in SARS-COV-2 coronavirus infection

Coronavirus infection caused by the SARS-CoV-2 virus is an extremely important and urgent problem of modern medicine. It spreads quickly, has a high probability of a severe course and a large number of critical complications in patients from the risk group. The presence of pathognomonic symptoms, one of which is the development of hypo– or anosmia, makes it possible to quickly differentiate coronavirus infection from other acute respiratory viral infections, that is, to isolate the patient on time and begin correct treatment, taking all possible risks into account. The aim is to identify the morphological features of olfactory structural elements in patients with coronavirus disease (COVID-19) for a better understanding of the mechanisms of olfactory disorders development in coronavirus infection. Materials and methods. The basis of the work is a retrospective analysis of autopsy material, namely the mucous membrane of the upper parts of the nasal cavity (olfactory epithelium) and olfactory bulbs of nine deceased (4 women and 5 men) aged from 53 to 79 years with a laboratory-confirmed diagnosis of COVID-19 and anosmia in anamnesis. We used standard hematoxylin and eosin staining and immunohistochemical reactions in accordance with the TermoScientific protocols (USA) with antibodies to neurospecific beta-III tubulin (clone TuJ-1) and RnDsystems protocols with antibodies to olfactory marker protein (OMP) and angiotensin converting enzyme (ACE-2). To compare the results, a control group of 9 deaths (3 women and 6 men) aged from 59 to 68 years with a laboratory-refuted diagnosis of COVID-19 was formed. The causes of death of these patients were complications of diabetes, coronary heart disease and cerebrovascular disorders of the ischemictype. Results. The average age of the deceased with a laboratory-confirmed diagnosis of COVID-19 and a history of anosmia and the control group was 64.67 ± 7.73 and 62.33 ± 6.48 years, respectively. The expression of olfactory marker protein (OMP) and neurospecific beta-III tubulin (clone TuJ-1) was partially positive (40.89 (25.00–52.00) and 42.44 (29.00–55.00) cells in the field of view at a magnification of 200×, respectively) in seven out of nine sections of the olfactory mucous membrane of deaths with a laboratory-confirmed diagnosis of COVID-19 and anosmia in anamnesis. The reaction with antibodies to angiotensin converting enzyme (ACE-2) was focally or subtotally absent (34.33 (14.00–49.00) cells in the field of view at 200× magnification). There was expression of these three markers in control sections of the olfactory mucosa of a deceased with a laboratory excluded diagnosis of COVID-19 and no symptoms of anosmia (Mann–Whitney test, P < 0.05). In sections of olfactory bulbs of patients with COVID-19 weak (Mann–Whitney test, P < 0.05) expression of receptors for angiotensin-converting enzyme (ACE-2) (26.78 (15.00–39.00) cells in field of view at a magnification of 200×) was revealed in contrast to control sections (100.56 (94.00–107.00) cells in the field of view at a magnification of 200×). Conclusions. The development of anosmia in SARS-CoV-2 coronavirus infection has specific features. This may be due to the primary destruction of cells expressing receptors for the angiotensin-converting enzyme (ACE-2-positive: sustentacular cells of the olfactory mucosa, neurons of the olfactory bulbs). Subsequent dysfunction of olfactory cells (OMP- and TuJ-1-positive) is also possible.

Olfactory function improves following hemodialysis

Olfactory function has been shown to be affected in chronic kidney disease; however, studies are contradictory and little is known on the effects of dialysis. To resolve these issues we tested olfactory function in 24 healthy controls and in 28 patients with chronic kidney disease receiving hemodialysis (20 patients) or peritoneal dialysis (the other 8). As assays for olfactory function we measured smell identification, n-butanol and acetic acid thresholds, Kt/V urea, percentage reduced urea, and weights before and after dialysis. Olfactory function was also self-rated by the participants. Compared to healthy controls, predialysis olfactory function was moderately but significantly decreased in the two dialysis groups, with hemodialysis patients being more affected. Patients self-rated olfactory function similar to that of healthy controls, suggesting that patients are unaware of the olfactory decrease. Olfactory function was significantly improved by one hemodialysis session. Neither body mass index, total volume loss, nor any other dialysis parameter correlated with olfactory function or its restitution following hemodialysis. The observed pattern of improvement suggests underlying mixed peripheral and central mechanisms. Thus, olfactory dysfunction in patients with chronic kidney disease is readily reversible by hemodialysis.

Chronic stress aggravates inflammation of nasal mucosa in allergic rhinitis-induced mice model

To investigate the effect of chronic stress on inflammation of nasal mucosa using an unpredictable chronic mild stress (UCMS) model to mimic chronic stress-like disorders. We divided BALB/c mice into four groups: control (n = 5), UCMS-exposed (n = 5), AR-induced (n = 5) and UCMS-exposed/AR-induced groups (n = 5). We measured cortisol as a marker of chronic stress and cytokines such as IFN-γ and IL-4, IL-5 representing Th1 and Th2 response, respectively, and we also examined the nasal mucous membrane histologically. UCMS exposure was confirmed by an increase in the levels of cortisol. Although there was no significant difference in Th1 cytokine (IFN-γ) levels within the groups, Th2 cytokine (IL-5) levels were significantly increased in stressed groups (UCMS-exposed and UCMS-exposed/AR-induced groups) compared to non-stressed groups (control and AR-induced groups). The histological examination of the nasal mucous membrane after antigen challenge in stressed group revealed severe dilation of blood vessels and injured olfactory hairs on the olfactory mucous membrane and severe swelling in the respiratory epithelium, compared to non-stressed group. These results suggest that chronic stress can aggravate inflammation of nasal mucosa in AR-induced mice model by shifting to the Th2 response by up-regulation of Th2 cytokines expression.

Bromocriptine, a dopamine d2 receptor agonist, inhibits adenylyl cyclase activity in rat olfactory epithelium

The presence of large numbers of dopaminergic neurons in the olfactory bulb suggests that dopamine plays an important role in olfaction. Dopamine D2 receptors are produced in olfactory sensory neurons [Shipley et al. (1991) Chem. Senses 16, 5] and found in relatively high concentrations in their terminals in the nerve and glomerular layers of the olfactory bulb [Nickell et al. (1991) NeuroReport 2, 9–12]. In other systems D2 receptors are linked to adenylyl cyclase by an inhibitory G-protein, and activation of the receptors results in inhibition of the enzyme. We examined rat olfactory mucous membrane to determine whether the D2 receptors were linked functionally to adenylyl cyclase as they are in other tissues. Adenylyl cyclase is found in both the olfactory cilia of the sensory epithelium and olfactory nerve terminals in the bulb. Bromocriptine, a D2 receptor agonist, was added to olfactory epithelium membrane preparations from normal and unilaterally bulbectomized adult rats and the preparations were assayed for forskolin-stimulated adenylyl cyclase activity. In unoperated animals bromocriptine significantly inhibited adenylyl cyclase activity, and the inhibition was abolished following pertussis toxin treatment. In mucosa from unilaterally bulbectomized animals we saw significantly lower adenylyl cyclase activity on the operated side and a further decrease in response to bromocriptine. The data indicate that bromocriptine decreases adenylyl cyclase activity in olfactory tissue, specifically in the sensory neurons, and the reaction is dependent on a pertussis toxin-sensitive G-protein. Given the absence of dopaminergic input to the olfactory epithelium, we propose that dopamine D2 receptors are more probably functionally linked to the adenylyl cyclase that is being transported to the axon terminals than to the adenylyl cyclase in cilia. The results also suggest that receptors are coupled to G-proteins before they are transported to nerve terminals.

Enzootic intranasal tumour of goats in Italy.

An outbreak of enzootic intranasal tumour (EIT) in a goat herd in Central Italy is described. From October 1990 to September 1992 41 tumors were diagnosed in goats ranging in age from 6 months to 6 years and of both the Alpine and Saanen breeds. Clinically the affected goats showed nasal discharge, facial swelling, sneezing and snoring respiration and weight loss. Post-mortem examinations revealed uni- or bilateral tumours of the olfactory mucous membrane. The neoplasms were classified as low grade adenocarcinomas. Ultrastructurally, retrovirus-like particles were observed in 10/10 tumours examined. Epidemiological and ultrastructural findings strongly suggest a viral aetiology for intranasal enzootic adenocarcinoma in the goats examined.

きゅう神経芽細胞腫例

It is said that olfactory neuroblastoma is an extremely rare carcinoma developing in the epithelium of the olfactory mucous membrane. In Japan its prognosis is poor.We recently treated a 49-year-old male with olfactory neuroblastoma. Intracranial infiltration was demonstrated by detailed examinations. Patients with intracranial infiltration have an extremely poor prognosis.We performed surgery, radiotherapy and chemotherapy (300mg of cis-diaminedichloroplatinum: CDDP).The patient is still alive without recurrence more than 3 years after surgery.

Selective infections of olfactory and respiratory epithelium by vesicular stomatitis and Sendai viruses.

Following intranasal instillation of vesicular stomatitis virus (VSV) in mice there was an extensive infection of the olfactory epithelium in contrast to a minimal involvement of the respiratory epithelium. Sendai virus (SV), on the other hand, caused an extensive infection of the respiratory epithelium and only minimal infection of the olfactory mucous membrane. VSV budded from basolateral surfaces of supporting cells and olfactory neurons, but not from their apical surfaces or the ciliated bulbous endings of the olfactory neuron dendrites. This asymmetric release of VSV favoured neuroinvasion. The virus spread along the olfactory nerves to the glomeruli in the olfactory bulbs after which it propagated transneuronally into the rest of the brain. SV budded only from the apical surface of respiratory epithelial cells, was released into the air passages, and there were no signs of invasion into the olfactory bulbs. Inoculation of the olfactory mucous membrane is a useful procedure for studies on selectivity of attack on peripheral neurons by viruses and on mechanisms of virus invasion of the nervous system in vivo.

ON THE SENILE OLFACTORY SENSE

Observation concerning the percentage of the number of the patients who were conscious of some olfactory disturbances among the patients with diseases either at nasal or paranasal cavities, and its relation to the age of the patients has led the author to conclude that very few infant as well as aged patients had the disturbances as their chief complaints. This may be explained by the fact in the cases of infant patients, their emotion and attentiveness are poorly developed, while in aged patients their number is few and conditions of the disease become worse during the long period of chronic diseases. Observation was made that 32.7% of the female patients at menopause were apparently conscious of the presence of some olfactory disturbances. The result of the olfactory test. however, was males. Moreover, the result of the olfactory test seemed to have no special correlation to climacteric symptoms. cious nervousness as well as decrease in olfactory sensation depend chiefly on the particularity of the mental condition, in other words, their complaints on olfactory disturbances are considered to be due to the mental condition aroused by such special rest before. The olfactory test undertaken in the persons from 10 to 85 years old who did not show any tivity was remarkable among the persons over 60 years old. ory center and olfactory organ of the people over 60 years old compared with those of normal adult ones were carried out. The results obtained are as follows: (1) Olfactory mucous membrane dermal cell layers lost their original shapes and sometimes disappeared. Processus lacken clearness and were swollen. In such cases the olfactory nerve fibers were swollen and sometimes were disconnected. Due to these changes decrease in stainability often caused difficulties in proving the presence of the nerve fibers. rlayers of the mucous membranes were expanded and congested, but the swelling of the walls was not so remarkable. the blood vessels were observed. In certain cases, hwever, the swelling of the peculiar membranes due to the accumulation of the secretion showed a tendency of dissolving character. (2) Olfactory center General course changes were seen, specially around the blood vssels. Regressive changes were present at the nerve cells. Pigmental atrophy was clearly observed. (3) Olfactory lobe crease of glia cells were seen. Occasionally necrotic nest were present. Blood vessels were dilated and swelling of the walls was also noticed. xylin were also present here as well as in the olfactory center. At the olfactory cord, both the multiplication of the glia cells and the necrotic change were most active. Pathohistological evidences which I believe to be useful to explain the cause of the decrease in the olfactory susceptibility of the people over 60 years old were obtained.

METHODS OF THE SMELL TEST

1) As the results of several examinations, we made the olfactorymeter almost satisfied various conditions, which made the basis inventing the smell tests.2) The smell tests were divided in three; pressure, dilution and venous olfactoiy test. Principle, apparatus and method of each of these tests were stated.3) From the results os these examinations, we could know of ihe olfactory disturbance dependent upon in nasal forms by pressure test and upon sensibility of olfactory mucous membrane by dilution test. venous olfactory test could survey for patients compelelty lost of nasal olfactory sense.

Olfactory nerve fibers.

Cross sections of olfactory nerves present a unique appearance. They indicate the presence of large numbers of very small nerve fibers, with a modal diameter of about 0.2 micro and a narrow range for their size variation. From one side of the nasal septum of a pig the yield of fibers was estimated at 6,000,000; the number arising from the turbinates would be considerably larger. The fibers are attached to the membranes of the Schwann sheaths in large bundles through mesaxons longer and more branched than those that have been seen in other nerves. Continuity of the axons between the nerves and the bipolar cells was traced in an examination of the olfactory mucous membrane; and the indication of a one-to-one relationship between cells and axons was reinforced by a comparative count. After the axons leave the bipolar cells they become incased in the central projections of the sustentacular cells. Where the latter come into contact with the basal cells the axons emerge to push back the plasma membranes of the basal cells in the first step in acquiring their nerve sheaths. Later steps are described. When the axons are delivered by the basal cells to the collecting Schwann tubes, they are already aggregated into small bundles with sheaths fundamentally the same as those they will possess until they are delivered to the glia in the olfactory bulb. Some of the aspects of the cytology of the bipolar cells and adjoining sustentacular cells are described. A survey of the physiological properties of olfactory nerve fibers was made in some experiments on the olfactory nerve of the pike. Almost all of the action potential is encompassed within a single elevation, manifesting at its front a conduction velocity of 0.2 m./sec. For a comparison, the last elevation in the C action potential in the sciatic nerve of the frog is cited as an example of conduction at the same velocity. Though expressed through long time constants, the properties of the pike olfactory fibers conform to the generalized schema for properties of vertebrate nerve fibers. This conformity signalizes that they differ from the exceptional properties of the unmedullated fibers of dorsal root origin. An afferent function for unmedullated nerve fibers does not imply that the fibers concerned are alike in their physiological properties.

Growth of the components of the human eyeball; II. Comparison of the calculated volumes of the eyes of the newborn and of adults, and their components.

THE CALCULATED volume of the eye of the newborn and that of an adult person are shown in table 1 of a previous paper (Wilmer and Scammon 1950) and are illustrated graphically here by charts 1 through 5. The entire eyeball increases a little less than threefold between birth and maturity. This postnatal gain is very small as compared with that of the body as a whole, which increases about twentyfold, and is even less than that of the brain, which increases about three and a half times in weight. However, the gain of the eyeball is greater than that of most of the organs of special sense; for instance, the internal ear remains almost constant in size from late fetal life to maturity, and the olfactory mucous membrane is presumed to increase 10 per cent or less in area. There is little evidence of any increase in the organ

PATHOLOGIC CHANGE IN OLFACTORY NASAL MUCOSA OF ALBINO RATS WITH "STUNTED" OLFACTORY BULBS

The occasional occurrence of small olfactory bulbs in the albino rat has been noted by Holt,1Sugita2and Donaldson and Hatai3and in my previous study.4These bulbs, which occur rather infrequently in young rats and which were designated as stunted by Sugita, were found to be present in all the senile rats studied.4The fact that the decrease in volume was apparently dependent on the loss of the entering olfactory fibers led me to obtain some further material in order that the olfactory mucous membrane and olfactory nerves might be studied along with the olfactory bulbs. The results of this study form the basis of the present communication. MATERIAL AND METHODS Twelve male albino rats of the experimental colony strain were obtained from the Wistar Institute for this investigation. These were of the same stock as those used in a previous study and like them were all normal rats

THE THALAMUS IN THE PHYSIOLOGY AND PATHOLOGY OF THE MIND

The role of the thalamus is one of the most interesting and most important problems. The thalamus is essentially the receptive or sensory portion of the primitive or segmental brain, the paleoencephalon. The relation it bears to the impacts which the organism receives from the outside world and to the transmission of these impacts to the neoencephalon, the cortex, gives it a significance and value altogether peculiar. Too often its importance is overlooked or, it may be, underestimated. When we turn our attention to the cephalic end of the nervous axis of a simple vertebrate form, such as a fish, we note the presence of certain aggregations of neurons which stand in definite relation to certain receptors. The first aggregation is that constituting the olfactory lobe; this is in close relation with the olfactory mucous membrane. Back of the olfactory lobe we note a lobe related to the receptors in