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Investigation of initial changes in the mouse olfactory epithelium following a single intravenous injection of vincristine sulphate.

To investigate initial changes in the olfactory epithelium, vincristine sulphate (VCR) was administered intravenously once to male BALB/c mice on day 1 in comparison with unilateral bulbectomy (UBT). The light and electron microscopy of the olfactory epithelium, nerve and/or bulb with BrdU-morphometry was performed sequentially. Further, whole-body radioluminography was conducted at 1 and 24 hours postdose. Apoptosis and an increased number of mitotic cells with a tendency toward decreasing BrdU-positive olfactory epithelial cell counts were observed in olfactory epithelial cells at 6 hours postdose of VCR and became more pronounced at 24 hours postdose. These changes disappeared on days 4 or 15, but minimal axonal degeneration was seen in the olfactory nerve from day 4 onward. Semiquantitative measurement of VCR levels in the ethmoturbinals elicited high drug retention even 24 hours after administration. In contrast, UBT showed no effect on mitosis and BrdU-positive cell counts at 6 hours postdose, but severe lesions in the olfactory epithelium and nerve were seen on days 2, 4, and/or 15. The above results suggest that the initial event of VCR-induced apoptosis in the mouse olfactory epithelium would be mitotic arrest with high drug retention, unlike that evoked by UBT.

Animals↗

[Morphology of olfactory bulb, olfactory tract blood supply affected by anthrosclersis and its clinical significance].

OBJECTIVE: In order to provide morphological evidences for olfactory defect cased by olfactory bulb, olfactory tract ischemia, the origins, numbers, distributions and pathological changes about olfactory bulb, olfactory tract arteries were studied. METHOD: The distributions and pathological changes of olfactory bulb, olfactory tract arteries in 80 sides of adult brain specimens were observed with operation microscope, among which the nourishing arteries and nerve of olfactory tract in two sides aged from 60 to 70 were observed pathohistologically. RESULT: The blood supply of olfactory bulb, olfactory tract comes mainly form artery cerebral and posterior communicainy. 10% of these 60 sides arteries were of multi-branch. 86.3% of them had atheroselerosis. 25.0% of the olfactory bulb and olfactory tract artery were blocked or narrow, and pathological changes in olfactory nerve such as atrophy were observed. CONCLUSION: Excluding other diseases, the olfactory defect in different degree of patients over 60 years old were caused possibly by atheroselerosis of the arteries at base of the brain.

Adult↗

Long term effects of Toki-shakuyaku-san on brain dopamine and nerve growth factor in olfactory-bulb-lesioned mice.

We used olfactory-bulb-lesioned mice induced by intranasal irrigation with zinc sulfate as a model of dementia, to investigate the effects of Toki-shakuyaku-san (TSS) on monoamines and nerve growth factor (NGF) in brain regions. TSS was given daily through the drinking water for either 1, 2, 3, 4 or 8 weeks from the day after olfactory lesion. The administration of TSS significantly suppressed the decrease of 3,4-dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA) in olfactory bulb of olfactory-lesioned mice at 1 week, and tended to suppress the decrease of DOPAC and HVA during the experimental session. However, the administration of TSS had no influence on dopamine contents. NGF contents in the olfactory bulb were increased after the irrigation, and the value returned to the same level as the control at 8 weeks after. Although the NGF contents in the olfactory bulb of TSS-treated mice were immediately increased at 1 and 2 weeks, the value returned to normal level within 3 weeks. These findings indicate that oral administration of TSS prevents the reduction of dopamine metabolites, DOPAC and HVA, and immediately increased NGF contents in the olfactory bulb. This suggested that TSS treatment promotes the NGF contents in olfactory nerves and rescue the neurons from damage.

3,4-Dihydroxyphenylacetic Acid↗

Regulation of main olfactory bulb mitral cell excitability by metabotropic glutamate receptor mGluR1.

In the rodent main olfactory bulb (MOB), mitral cells (MCs) express high levels of the group I metabotropic glutamate receptor (mGluR) subtype, mGluR1. The significance of this receptor in modulating MC excitability is unknown. We investigated the physiological role of mGluR1 in regulating MC activity in rat and mouse MOB slices. The selective group I agonist (RS)-3,5-dihydroxyphenylglycine (DHPG), but not group II or III agonists, induced potent, dose-dependent, and reversible depolarization and increased firing of MCs. These effects persisted in the presence of blockers of fast synaptic transmission, indicating that they are due to direct activation of mGluRs on MCs. Voltage-clamp recordings showed that DHPG elicited a voltage-dependent inward current consisting of multiple components sensitive to potassium and calcium channel blockade and intracellular calcium chelation. MC excitatory responses to DHPG were absent in mGluR1 knockout mice but persisted in mGluR5 knockout mice. Broad-spectrum LY341495, MCPG, as well as preferential mGluR1 LY367385 antagonists blocked the excitatory effects of DHPG and also potently modulated MC spontaneous and olfactory nerve-evoked excitability. mGluR antagonists altered spontaneous membrane potential bistability, increasing the duration of the up and down states. mGluR antagonists also substantially attenuated MC responses to sensory input, decreasing the probability and increasing the latency of olfactory nerve-evoked spikes. These findings suggest that endogenous glutamate tonically modulates MC excitability and responsiveness to olfactory nerve input, and hence the operation of the MOB circuitry, via activation of mGluR1.

Animals↗

Anatomy and morphometry of the olfactory organ of the wels Silurus glanis L. (Siluridae, Pisces).

The anatomical structure of the olfactory organs, nerve tracts and brain was described in Silurus glanis. The changes connected with aging were considered. The olfactory lamellae are thin and tightly set in a rosette. In the 1 year old individuals there are 48...51 lamellae in a single rosette. This number increases gradually with age and in the 9...10 year old welses reaches 150. The surface area of the lamellae of a single rosette also indicates an increase: in the 1 year old specimen it equals 117 mm2, while in the adult individual (5...6 year old)--1040 mm2. This is due to the increase in both the size of each lamella and the number of the lamellae. The obtained results are discussed with regard to other author's data. It has been found that the dynamics of the increase of the surface area of the olfactory epithelium in fish are closely related to the way of life and not to the systematic affiliation of the species.

Aging↗

Nerve growth factor promotes olfactory axonal elongation.

An explant culture system was used to test the effect of nerve growth factor (NGF) on olfactory axonal elongation. Statistical analysis showed that exogenously applied NGF (50 ng/ml) significantly enhanced olfactory neurite elongation from E14 rat olfactory epithelial explants (p = 0.025). Immunostaining showed that the neurites expressed active TrkA receptors and that S-100-positive ensheathing cells were also present. In a separate experiment, immunoassay confirmed that following a growth period of 72 h, E14 presumptive olfactory bulb expressed and secreted NGF into the culture medium. The results indicate that during ontogeny, the olfactory bulb secretes NGF which binds to olfactory axons and facilitates their elongation.

Animals↗

Demonstration of terminalis, olfactory, trigeminal and perivascular nerves in the rat nasal septum.

The innervation of the nasal septum and around the olfactory bulb has been investigated in rats by means of whole-mount preparations and histological sections. Silver staining, OsO4 staining, PAS staining, cholinesterase reaction and fluorescence for catecholamine-containing nerves were used. The nervus terminalis forms on the medial side of the olfactory bulb a ganglionated plexus, from which branches are given off which course peripherally with the vomeronasal nerves. From a dorsal part of the terminalis nerve plexus an anterior branch is given off which runs along the anterior ethmoidal nerve to the nasal vestibule where it connects with a group of ganglia. The peripheral branches of the nerve run from here along two epithelial cristae formed histologically like dermal papillae. Ventrally in the respiratory region at the junction of the nasal cavity and the nasopharynx is a 1 times 2 mm area with olfactory epithelium, glands of Bowman and an independent innervation from the olfactory bulb. This is the so-called septal olfactory organ. Trigeminal nerves form a plexus in the respiratory region and in the vestibule, but do not supply the olfactory region. Catecholamine-containing and cholinesterase-positive nerves run along the meningeal arteries on the cribriform plate and accompany their branches to the vascular plexus in the olfactory and respiratory regions. Double innervation is found not only of this vascular plexus but of the venous sinuses in the swell bodies of the vestibule. The glands of the nose are not surrounded by catecholamine-containing nerves.

Animals↗

Projections of two subclasses of vomeronasal nerve fibers to the accessory olfactory bulb in the rabbit.

The organization of the projections of subclasses of vomeronasal nerve fibers to the accessory olfactory bulb was analysed using monoclonal antibodies generated against a homogenate of the rabbit olfactory bulb. Monoclonal antibody R2D5 labels all the somata of vomeronasal receptor cells in the vomeronasal organ as well as all their axons (vomeronasal nerve fibers). Another monoclonal antibody (R4B12), which has been shown to selectively bind and thus identify a subclass of olfactory nerve fibers, also labels a subclass of vomeronasal nerve fibers. The R4B12-positive subclass of vomeronasal nerve fibers project to the glomeruli in the rostrolateral part of the accessory olfactory bulb. The third monoclonal antibody (R5A10) recognizes a complementary subclass of vomeronasal nerve fibers projecting to the glomeruli in the caudomedial part of the accessory bulb. In contrast to the clearly segregated terminations in the accessory bulb, the two subclasses of vomeronasal nerve fibers are intermingled with each other in the vomeronasal nerve bundles. Retrograde labeling of vomeronasal receptor cell somata following injection of horseradish peroxidase within the rostrolateral (R4B12-positive) part of the accessory bulb indicates that vomeronasal receptor cells of this subtype are widely distributed in the vomeronasal sensory epithelium. These results demonstrate the heterogeneity of vomeronasal receptor cells and the specificity of projections arising from subclasses of vomeronasal nerve fibers to the accessory olfactory bulb.

Animals↗

Anosmin-1 immunoreactivity during embryogenesis in a primitive eutherian mammal.

Kallmann syndrome is hypogonadotropic hypogonadism coupled with anosmia. A morphological study found that the endocrine disorder in X-linked Kallmann syndrome is due to failed migration of gonadotropin releasing-hormone (GnRH) neurons from the olfactory placode to the brain during development. Anosmia results from agenesis of the olfactory bulbs and tracts. The gene responsible for the X-linked form of Kallmann syndrome, KAL-1, has been characterized. The orthologues of KAL-1 have been isolated in the chick and the zebrafish, but still await identification in rodents. In the present study, we used polyclonal and monoclonal antibodies to the human KAL-1 encoded protein, anosmin-1, in a primitive mammal, the Asian musk shrew. Musk shrews are insectivores and are therefore evolutionarily closer to primates than rodents. By immunoblot analysis of musk shrew tissues, a band of the expected apparent molecular mass (95 kDa) was detected in several structures of the central nervous system, but not in liver or muscle, which is consistent with the gene expression pattern previously reported in the chick. By immunohistochemical analysis, anosmin-1 was detected in the developing olfactory epithelium, the olfactory, vomeronasal and terminalis nerves, the olfactory bulbs, the cerebellum and the cerebral cortex and in several other regions of the brain, during musk shrew embryogenesis. Furthermore, migrating gonadotropin releasing-hormone (GnRH)-immunoreactive neurons were seen in close association with anosmin-1-immunoreactive fibers. Assuming that the protein is present at the surface of these fibers, we suggest a possible direct role of anosmin-1 in the migration of GnRH neurons in this species.

Animals↗

Central projections of the nervus terminalis in four species of amphibians.

The central projections of the nervus terminalis were investigated in two anuran and two urodele species by means of horseradish peroxidase injections into one nasal cavity. In anurans, the nervus terminalis projects to the medial septum, to the preoptic nucleus, to the nucleus of the anterior commissure and to the hypothalamus. In addition to these structures, the dorsal thalamus, the infundibulum and the mesencephalic tegmentum are innervated in urodeles. The structure containing the highest density of terminals in the amphibians investigated is the hypothalamus. In one anuran and one urodele species, the contralateral hypothalamus is primarily innervated, whereas in the other two species the majority of fibers remain ipsilateral. A comparison with other vertebrates shows that the terminalis system in urodeles has the greatest diversity of connections. Anurans, in contrast, lack some connections that are present in urodeles and fishes. These findings have implications for a possible relation of the nervus terminalis to an aquatic habitat.

Ambystoma mexicanum↗

[Studies on chemotactic behaviors of Strongyloides ratti infective larvae in vitro and migration routes of the larvae in rat head].

For the purpose of clarifying host-finding mechanisms, the infective larvae of Strongyloides ratti were run on an agarose plate which had been placed various attractants around the larvae. They were accumulated at the sites of sodium compounds, serum proteins and albumins. At 20, 30, 40 hours after infection, rats were killed and heads were separated. They were then processed for thin section specimens. Larvae were found in brains, olfactory bulbs and its nerves. These larvae seemed to move along olfactory nerves during descending from the cranial cavity. Another migration study was done by whole body autoradiography after 35S-methionine labeling for clarifying the larval pathway how to invade cranial cavity in the rats. They first crawled under subcutaneous region of rat and then accumulated at the tip of the nose. Next, they began to ascend olfactory nerves. They were in cranial cavity up to 20 hours after infection and then descending same route to nasal cavity. I don't know why they aim the cranial cavity but they had necessity to invade the cranial cavity and stay there for appropriate time to be an adult in the intestine.

Animals↗

Management of a sporadic malignant subfrontal peripheral nerve sheath tumor.

Malignant subfrontal (olfactory) peripheral nerve sheath tumors (MPNSTs) are exceedingly rare. Although meningiomas are the most common subfrontal extra-axial lesions, it is important to recognize that MPNSTs, which are radiographically similar to meningiomas, can also be present in this location. MPNSTs require more aggressive surgical and postoperative management than meningiomas. In this paper, we describe a patient with a subfrontal MPNST with unusual histological characteristics and present a review of the literature. A 49-year-old woman presented with chronic sinusitis and progressive headaches. A neurological examination revealed left-sided anosmia. Brain-imaging studies revealed a large left subfrontal mass with extension into the frontal and ethmoid sinuses and the nasal cavity. The patient underwent both a bifrontal transbasal craniotomy and a transnasal approach for an attempt at total resection of both the intradural and extradural components of the MPNST. The patient was treated postoperatively with radiation therapy, and had no evidence of recurrence at her follow-up examination 1-year after treatment. Subfrontal PNSTs are extremely rare and usually benign. The specific cell and nerve of origin for these tumors remains unknown. Our case shows that these rare lesions can present as a malignant variant and thus require aggressive surgical and postoperative management to provide long-term tumor control.

Adult↗

Breathing and upper airway CO2 in reptiles: role of the nasal and vomeronasal systems.

The ventilatory response of the garter snake, Thamnophis sirtalis, to 2% CO2 delivered to the upper airways (UA) was measured before and after the olfactory or vomeronasal nerves were transected. The UA (nasal cavities and mouth) were isolated from the gas source inspired into the lungs by inserting an endotracheal T tube into the glottis. CO2 was administered to the UA via a head chamber. The primary ventilatory response to UA CO2 was a significant decrease in ventilatory frequency (f) and minute ventilation. The decrease in f was caused by a significant increase in the pause duration. Tidal volume, expiratory duration, and inspiratory duration were not altered with UA CO2. The f response to UA CO2 was abolished with olfactory nerve transection, whereas vomeronasal nerve transection significantly increased the magnitude of the f depression. These results indicate that CO2-sensitive receptors are located in the nasal epithelium and that the olfactory nerves must be intact for the UA CO2 f response to be observed. In addition, the vomeronasal system appears to modulate the ventilatory response to UA CO2.

Animals↗

Lectin identification of olfactory receptor neuron subclasses with segregated central projections.

Our previous studies have demonstrated that the primary olfactory projection in rainbow trout is organized nontopographically; the pattern of termination of olfactory axons in the olfactory bulb is unrelated to the distribution of their cell bodies in the olfactory mucosa. In the present research we have further characterized the organization of this projection by examining the lectin-binding properties of olfactory receptor neurons. The results indicate that in trout, as in mammals, populations of olfactory receptor neurons differ significantly from one another in their carbohydrate "signatures." We have identified subsets of olfactory receptor neurons, specified by unique lectin-binding properties, that are widely distributed and intermingled with the other receptor neurons in the olfactory mucosa and nerve, but that segregate as they enter the olfactory bulb and project to restricted regions of the glomerular layer. This pattern of terminations is bilaterally symmetrical, is remarkably consistent across individuals, and reappears when the primary olfactory projection is reconstituted following transection of the olfactory nerve. As revealed by the carbohydrates on subpopulations of receptor neurons, there is substantial order in the nontopographic projection of olfactory receptor neurons to the olfactory bulb. The functional significance of this organization and the means by which it develops and is maintained remain under investigation.

Animals↗