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PubMed1989

Induction of tyrosine hydroxylase expression in rat forebrain neurons.

Olfactory nerve input is required for the normal expression of tyrosine hydroxylase (TH) by dopaminergic neurons in the glomerular region of the rodent main olfactory bulb. To determine whether the olfactory nerve exerts a similar influence on neurons in other brain regions, we performed unilateral bulbectomies in rat pups on postnatal day 5-7 and examined the brains 2-6 months later, after the regenerated olfactory nerve had penetrated the forebrain. Tissue was stained for TH, dopamine beta-hydroxylase (DBH) and olfactory marker protein immunoreactivity. We observed novel TH-immunoreactivity in neurons located in those areas of the adult forebrain which received olfactory nerve fibers, particularly the rostral extension of the subependymal layer. Many of these neurons resembled the periglomerular cells of the olfactory bulb. No cell staining for DBH was observed in these areas, suggesting the possible dopaminergic phenotype of these neurons. Our data indicate that afferent regulation of neurotransmitter expression by the olfactory nerve is not limited to the cells of the olfactory bulb.

Animals↗

PubMed1996

Expression and localization of FGF-1 in the developing rat olfactory system.

Primary olfactory axons project from the nasal olfactory neuroepithelium to glomeruli in the olfactory bulb where they synapse with mitral cells, the second-order olfactory neurons. We have shown that the heparin-binding growth factor FGF-1 is expressed by olfactory nerve ensheathing cells which surround fascicles of primary olfactory axons en route to the olfactory bulb. These cells are believed to modulate olfactory axon growth between the olfactory neuroepithelium and the olfactory bulb. During late embryogenesis, FGF-1 expression is turned on in the mitral cells, and the FGF-1 peptide becomes confined to layers of synaptic neuropil in the postnatal olfactory bulb. FGF-1 is selectively present in glomeruli and the external plexiform layer. In cultures of olfactory neuroepithelial cells, complexes between FGF-1 and an appropriate activating heparan sulfate proteoglycan stimulated morphological differentiation of both olfactory nerve ensheathing cells and primary sensory olfactory neurons. Thus, the spatiotemporal expression and the functional properties of FGF-1 in this system suggest that this molecule plays an important regulatory role in the formation of the olfactory pathway.

Animals↗

PubMed1995

Restoration of olfactory mediated behavior after olfactory bulb deafferentation.

Transection of olfactory nerve fibers leads to deafferentation of olfactory bulbs and a loss of olfactory mediated behavior. Nerve transection studies have shown that during recovery, olfactory nerve fibers can reestablish connections with the olfactory bulbs. Two groups of experimental animals were studied to determine if olfactory mediated behavior returns after recovery. One group (n = 18) received bilateral olfactory nerve transection (BTX), while the second group (n = 4) received a sham surgical procedure. Performance on odor detection and discrimination tasks was measured during recovery periods ranging from 1-120 days. Return of olfactory mediated behavior was first observed 19 days after nerve transection. Performance levels improved with recovery time and by day 40 animals returned to criterion level (> or = 90% correct response). Sham animals maintained a criterion level of performance throughout the recovery period. Horseradish peroxidase (HRP) was used to trace reconnection of olfactory nerve fibers. The absence of HRP label in the bulbs of animals examined one day after BTX, verified the completeness of the nerve transection procedure. After 10 days of recovery, a few HRP labeled axons were observed and the amount of HRP in the bulb increased with recovery time. The results of this study demonstrate that olfactory receptor axons can reestablish functional connections with the deafferented olfactory bulb and these connections are sufficient to restore olfactory mediated behavior.

Animals↗

PubMed1995

Straying phenomenon of migrating LHRH neurons and highly polysialylated NCAM in the chick embryo.

The present study on unilaterally incompletely placodectomized chick embryos revealed that arrival of migrating LHRH neurons into the forebrain area is dependent on the presence of a central projection of the olfactory nerve. When a fragment of the lateral and medial olfactory epithelium was spared the damage, a small number of LHRH-ir cells were found to migrate into the forebrain along a thin NCAM-H-expressing fiber bundle of the olfactory nerve. In embryos with large lesions which destroyed the lateral olfactory epithelium, the poorly developed NCAM-H-positive olfactory nerve fibers were arrested where they meet the NCAM-positive medial nasal branch of the ophthalmic nerve and frequently fused with this branch fiber bundle. In these embryos, no LHRH-ir cells were detected in the forebrain area. They were deviated from their regular migratory course to the NCAM-H-positive medial nasal branch fiber bundle. This straying phenomenon indicates that some structural support is apparently needed for the migration of LHRH-ir cells, but their migratory route is not completely programmed in their precursor cells in the olfactory placode. In cultures of placodal tissues, the coexistence of migrating LHRH-ir cells with NCAM-H-expressing neural elements was always confirmed. It is suggested therefore that not only the structural support for the migration but also the interaction between LHRH-ir cells and NCAM-H-expressing neural elements is a prerequisite for successful LHRH neuronal migration.

Animals↗

PubMed2003

Pneumococcal carriage results in ganglioside-mediated olfactory tissue infection.

Streptococcus pneumoniae cause considerable morbidity and mortality, with persistent neurological sequelae, particularly in young children and the elderly. It is widely assumed that carriage occurs through direct mucosal colonization from the environment whereas meningitis results from invasion from the blood. However, the results of published studies can be interpreted that pneumococci may enter the brain directly from the nasal cavity by axonal transport through olfactory nerves. This hypothesis is based on findings that (i) teichoic acid of the pneumococcal cell wall interact with gangliosides (GLS), (ii) the interaction of GLS with cholera toxin leads to axonal transport through the olfactory nerves into the brain, and (iii) viruses enter the brain through axonal transport into olfactory nerves. After nasal inoculation, we observe high numbers of pneumococci in nasal washes and the olfactory nerves and epithelium. Significant numbers of pneumococci also infected the olfactory bulbs, brain, and the trigeminal ganglia. The absence of bacteremia in this model makes it unlikely that the bacteria entered the brain from the blood stream. Recovery of colony-forming units from the brain, lungs, olfactory nerves, and epithelium and nasal washes was inhibited by incubating pneumococci with GLS before nasal inoculation. These findings, confirmed by PCR and immunohistochemistry, support a GLS-mediated process of infection and are consistent with pneumococci reaching the brain through retrograde axonal transport.

Animals↗

PubMed1992

Postoperative anosmia after removal of pituitary gland adenomas using the pterional approach.

There have been several studies on anosmia following operations on anterior circulation aneurysms, but no similar study has yet been reported on pituitary gland adenomas which required the transcranial approach. In this study, 38 cases with pituitary gland adenomas, for whom the pterional approach was employed, were observed retrospectively from the point of view of postoperative olfactory nerve function. In the postoperative period only one case complained of impaired sense of smell on the operated side. Eight cases objectively showed olfactory nerve dysfunctions. The olfactory nerve function could be preserved at a relatively high rate of 79 per cent. This high rate, we think, resulted from the microtechnique employed as well as the relatively cautious frontal retraction which was less than 1.5 cm.

Adenoma↗

PubMed1996

Uptake of 203Hg2+ in the olfactory system in pike.

Inorganic mercury (203Hg2+) was applied to the olfactory chambers or was given i.v. to pike (Esox lucius) and the uptake of the metal in the olfactory system and the brain was examined by autoradiography and gamma spectrometry. Application of 203Hg2+ in the olfactory chambers resulted in an accumulation of the metal in the olfactory nerves and the anterior parts of the olfactory bulbs of the brain. The levels of 203Hg2+ in other brain areas, such as the telencephalon, the optic tecti and the cerebellum, remained low. Application of 203Hg2+ in only one olfactory chamber resulted in an uptake of the metal only in the ipsilateral olfactory nerve and olfactory bulb. Intravenous injection of the 203Hg2+ resulted in a labelling of the olfactory system and the brain, which was much lower than of the blood. These results indicate that the 203Hg2+ is taken up in the olfactory neurones from the olfactory receptor cells in the olfactory rosettes and is transported to the terminal parts of the olfactory neurones in the olfactory bulbs. The uptake of mercury as well as some other metals in the olfactory system may result in noxious effects and this may be an important component in the toxicology of metals in fish.

Animals↗

PubMed1996

Olfactory responses of a euryhaline fish, the rainbow trout: adaptation of olfactory receptors to sea water and salt-dependence of their responses to amino acids

Salmonid fishes are able to survive in both fresh water and sea water. Concentrations of NaCl in fresh water and sea water are 0.5 and 493 mmol l-1, respectively, and, hence, salt concentrations in the medium at the olfactory epithelium are greatly changed when the fish migrate between fresh water and sea water. We used the rainbow trout, which is a salmonid fish, to examine the adaptation mechanisms of the olfactory receptors to high concentrations of salts in sea water. Application of sea water to the olfactory epithelium elicited only a very small response in the olfactory nerve, but 500 mmol l-1 NaCl elicited a large response which did not adapt to a spontaneous level with time. It is considered that the olfactory nerve becomes fatigued when the olfactory epithelium is exposed to 500 mmol l-1 NaCl for long periods. We found that the presence of 10 mmol l-1 Ca2+ in sea water inhibited the response to 500 mmol l-1 NaCl, suggesting that Ca2+ in sea water is essential for adaptation of the olfactory receptors to sea water. In the second part of the study, we examined whether the olfactory nerve responses to amino acids, potent stimulants for fish, were altered between fresh water and sea water. The magnitudes of the responses to the six amino acids examined were similar in artificial pond water and artificial sea water, indicating that a large change in NaCl concentration between fresh and sea water does not affect the olfactory nerve responses to amino acids. We used fish reared in fresh water and fish acclimated to sea water and obtained similar results. It was concluded that the tolerance of the olfactory receptors for large changes in osmotic pressure is not acquired while fish are maintained in fresh or sea water, but that the receptors of these euryhaline fish naturally provide the tolerance.

Journal Article↗

PubMed1987

Microtubules of frog olfactory axons: their length and number/axon.

Counts of the number of microtubule profiles in cross-sections of axons of bullfrog olfactory nerves indicates that about 80% of them have 2 or 3 microtubules, regardless of whether one samples axons in the proximal or distal ends of the nerve. In the olfactory lobe of the brain, however, only 50% of the axon profiles showed 2 or 3 microtubules. In the brain, 30% of the olfactory axons showed 4 or more microtubule profiles, compared with only 4% in axons sampled from the nerve proper. By following microtubule profiles in sets of serial cross-sections of frog olfactory axons, data were obtained indicating that, in the olfactory nerve proper, the average length of the microtubules is about 400 microns. In olfactory axons sampled in the brain, however, the average microtubule length is about 5-fold less than that found for microtubules in the nerve proper. The evidence suggests that as the olfactory axons approach their synaptic terminations in the brain, the microtubules become fragmented into shorter segments which may reflect their depolymerization.

Animals↗

PubMed1994

NADPH-diaphorase localization in the olfactory system.

NADPH-diaphorase staining was studied in the intact olfactory system and following transections of the olfactory nerve. Intense staining was found in the olfactory epithelia of rat and salamander, especially at the mucosal surface. The olfactory bulb nerve and glomerular layers were also stained. Transection of the olfactory nerve in salamander, or bulbectomy in rat, resulted in decreased staining at the mucosal surface, although staining increased in cells deeper in the epithelium. Deafferentation also caused the disappearance of staining in the olfactory nerve and glomerular layers of the bulb. These results support the notion of a role for NADPH in the olfactory system, perhaps as a biosynthesis substrate for NO modulation of cGMP in the developing epithelium and a complementary role for CO in the adult.

Animals↗

PubMed1987

Myelinated and nonmyelinated nerves: comparison of proton MR properties.

The magnetic resonance (MR) relaxation rates of protons were compared in the myelinated and nonmyelinated nerves of the garfish. The long, large olfactory nerve of the garfish, as an easily accessible source of nonmyelinated axons, is uniquely suited for such a comparison. The T1 and T2 measurements revealed distinct and consistent differences between nonmyelinated olfactory nerves and myelinated optic and oculomotor nerves. Comparisons between water content, lipid content, and relaxation rates indicated that the differences in MR properties represent complex differences in the distribution and physical environment of the constituent lipid and water protons.

Animals↗

PubMed1988

Responses of mitral/tufted cells to orthodromic and antidromic electrical stimulation in the olfactory bulb of the tiger salamander.

1. Responses evoked by electrical stimulation of the olfactory nerve and olfactory tracts were analyzed in 46 output cells of the salamander olfactory bulb, in vivo. Labeling of several cells with horseradish peroxidase indicated that they were mitral and/or tufted neurons. The responses contained reproducible sequences of depolarizing and hyperpolarizing potentials, which changed with increases in stimulus intensity. 2. Stimulation of the nerve with intensities subthreshold for evoking spikes in the recorded cell resulted in a small depolarization followed by a period of hyperpolarization, during which spontaneous spikes were suppressed. With suprathreshold stimulus intensities, a single spike or often a burst of spikes was evoked, followed by a complex prolonged hyperpolarization. When full spikes were blocked by injecting hyperpolarizing current through the recording electrode, an excitatory postsynaptic potential (EPSP) with two major components and sometimes a fast prepotential were observed at the beginning of the response. Amplitudes of the EPSP and hyperpolarization increased with graded increases in stimulus intensity. In tests with paired stimulus volleys, spike generation was inhibited for at least 1 s and often for several seconds during the hyperpolarization. 3. Stimulation of the tracts with intensities subthreshold for evoking spikes in the recorded cell resulted in a complex prolonged hyperpolarization. With suprathreshold stimulus intensities, a single spike was evoked, followed by a similar period of hyperpolarization. When full spikes were blocked by injecting hyperpolarizing current through the recording electrode, a small antidromic spike, presumably generated in the axon or initial segment, was often observed. Amplitude of the hyperpolarization increased with graded increases in stimulus intensity. In tests with paired volleys, generation of a full antidromic spike was inhibited for a period that usually began 20-30 ms, following the spike evoked by the conditioning stimulus and lasted 100-500 ms. Full antidromic spikes were evoked prior to the period of inhibition and small antidromic spikes were evoked during the period. 4. The mean latencies of single evoked spikes or the first spikes of bursts decreased from 22 to 17 ms with increases in the intensity of nerve stimulation and from 7 to 6 ms with increases in the intensity of tract stimulation. Only decreases in orthodromic latency were significant at P less than or equal to 0.05, as determined by one-sided t tests between the means of responses subdivided according to response pattern and relative stimulus intensity.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1989

[Immunohistochemical study on the primary olfactory neuron of rat and suncus].

Carnosine (beta-alanyl-L-histidine), a putative neurotransmitter, was identified immunohistochemically in the primary olfactory neuron, using newly developed anti-carnosine antiserum. Similar results were obtained in the rat and suncus. Carnosine-like immunoreactivity was observed in the olfactory cells and its apical dendrites of the olfactory epithelium. The olfactory nerve and glomerular layer of the olfactory bulb showed positive reaction. At electron microscopic level, carnosine-immunoreactive end products widely spread out in the cytoplasm of olfactory nerve cells and also on microtubules of olfactory cilia. In the glomerular layer, reaction products were found diffusely in many axon terminals. These terminals had small spherical vesicles and often made asymmetric synaptic contacts to the second neuron. Unilateral closure of the olfactory naris resulted lower immunoreactivity of tyrosine hydroxylase in periglomerular cells, which are dopaminergic interneurons and are thought to regulate neurotransmission of olfactory input. In contrast no remarkable changes were seen on carnosine immunoreactivity in olfactory bulb. The present results suggest that carnosine may play some important roles in the olfactory mucosa. The functional role of carnosine remarks to be further examined.

Animals↗

PubMed1998

[Calretinin immunoreactivity in olfactory bulb and mucosa in mice].

The vertebrate olfactory system is capable of recognizing and discriminating thousands of different odorant molecules. In vitro biochemical studies have shown that some odorants elicit an increase in the intercellular second messenger cyclic AMP, whereas other odorants cause an increase in the second messenger inositol triphosphate (IP3). If IP3 plays an important role in the signal transduction, calcium-binding protein will be needed. We investigated the expression of calretinin, which belongs to the E-F hand family, in the neonatal and adult olfactory mucosa and olfactory bulb. Mice were sacrificed on postnatal day 1 (P1), day 3 (P3), day 10 (P10) and 12 weeks as adults. The olfactory mucosa of the nasal septum and the olfactory bulb were stained with anti-calretinin antibody at a 1:1000 dilution for 48 hours. The results were as follows. 1) Olfactory mucosa: In the P1 mouse, the olfactory nerves running in the submucosal layer and olfactory cells in the epithelium were positive. In the epithelium, immunopositive spots were seen exclusively in the upper half of the epithelium. In the P3, P10 and adult mice, these spots were seen throughout the olfactory cell layer. However, the basal cell layer and supporting cells were negative. 2) Olfactory bulb: In all stages, the olfactory nerve layer and the glomerular layer were strongly stained. In the external plexiform layer, many cells were positive. Their shape was bipolar and the size of the cell body was thought to be about 20 microns. They were thought to be tufted cells. However, there is a possibility that these cells are short axon cells in the external plexiform layer. In the granule layer, some granule cells were positive. In the P1 mouse, the immunopositive spots were exclusively seen in the upper half of the epithelium. In contrast, in the P3 mouse, these spots were seen throughout the olfactory cell layer. Judging from our results, it is suspected that the important change in neurogenesis of olfactory cells occurred between P1 and P3. In the olfactory bulb, from P1 to adult mice, calretinin was positive in the olfactory nerve layer, the glomerulus and periglomerular cells. In contrast, mitral cells were negative. Most reports state that calcium binding protein appears in periglomerular cells. However, in the external plexiform layer, many cells were positive. As their shape was bipolar and the cell body was a little larger than the periglomerular cells, these cells were thought to be tufted cells.

Animals↗

PubMed1996

Ultrastructural study of ensheathing cells in early development of olfactory axons.

Ultrastructural observations in the grey short-tailed opossum (Monodelphis domestica) and rat revealed that ensheathing cells were intimately related to the early formation of olfactory axons. Whilst the axons were still in the olfactory epithelium, they were enveloped by ensheathing cell processes which formed a cradle-like structure on the basal side of the epithelium. Continued downgrowth of the axons towards the lamina propria resulted in an evagination with the ensheathing cell process or cell body in direct contact with the basal lamina. Subsequently the basal lamina became fragmented, and the newly formed olfactory nerve emerged from the olfactory epithelium. As the olfactory nerve grew, it was observed that the ensheathing cell process always extended ahead of the axons while axon terminals moving ahead of ensheathing cells were never observed. The findings in this study suggest that ensheathing cells play a role in regulating and promoting olfactory axon growth.

Animals↗

PubMed1991

An immunocytochemical study of the development of the olfactory system in the three-spined stickleback (Gasterosteus aculeatus L., Teleostei).

Antisera against a variety of substances have been found to produce an identical immunoreaction in the developing olfactory system of a teleost, the three-spined stickleback (Gasterosteus aculeatus). The label is localized in the olfactory placode, the olfactory nerve and those parts of the secondary olfactory tracts which constitute the dorsal descending fascicles and the ventral descending fibers of the medial olfactory tract. The label was first detected 3 days after fertilization (3D) in the olfactory placode where labeled supporting cells were observed. At 4D, the label was observed at the site of the developing olfactory bulbs. At 7D, the olfactory placode lost the direct contact with the brain and the labeled olfactory nerve became visible. At the same time, the medial olfactory tract emerged from the bulbs, and contacts with cells in the nucleus of the terminal nerve were observed. The development of the medial olfactory tract proceeded caudally, and by the end of 10D, the olfactory tract reached the periventricular hypothalamus. Pre-absorption of the antisera with the respective antigens did not abolish the capacity of the antisera to produce the label. The immunoreaction is thus not specific for the antigens against which the antisera have been raised. Yet the label produced by the immunoreaction is an extremely reliable marker for the primary olfactory tract, and the only existing marker by which secondary olfactory tracts can be visualized.

Animals↗

PubMed1989

MAP 1A and MAP 1B are structurally related microtubule associated proteins with distinct developmental patterns in the CNS.

Five high-molecular-weight microtubule-associated proteins (MAPs) were identified in brain tissue in previous work from this laboratory (Bloom et al., 1984). These proteins were termed MAP 1A, 1B, 1C, 2A, and 2B. The MAP 1's differed from the MAP 2's, and showed little evidence of interrelationship on the basis of immunological and biochemical comparison. We report here that MAP 1A and MAP 1B are, in fact, related at the level of subunit composition. Immunoprecipitation of the individual MAPs showed that both contained low-molecular-weight subunits of Mr 30,000 and Mr 19,000 (light chains 1 and 3). An additional subunit, light chain 2 (Mr 28,000), was primarily found in preparations of MAP 1A. The light chains co-sedimented with microtubules after chymotryptic digestion of the MAPs. This suggested an association of the light chains with the microtubule binding domains of the MAPs, which are identified here as distinct fragments of Mr 60,000 for MAP 1A and 120,000 for MAP 1B. A panel of monoclonal anti-MAP 1A and anti-MAP 1B antibodies, including one that reacts with a common phosphorylated epitope, was used to examine the distribution of these proteins in the developing rat brain and spinal cord. MAP 1B was found to be abundant in the newborn brain and to decrease with development, in contrast to MAP 1A which increased with development. By immunohistochemistry MAP 1B was found to be highly concentrated in developing axonal processes in the cerebellar molecular layer, the corticospinal tract, the mossy fibers in the hippocampus, and the olfactory nerve. Of particular interest, the mossy fiber and olfactory nerve staining persisted in the adult, indicating continued outgrowth of the mossy fibers as well as olfactory nerve axons. MAP 1A staining was, in contrast, weak or absent in developing axonal fibers but moderate in mature axons and intense in developing and mature dendritic processes. Our results indicate that MAP 1A and MAP 1B are structurally related components of the neuronal cytoskeleton with complementary patterns of expression.

Animals↗

PubMed1985

Immunohistopathology of human olfactory epithelium, nerve and bulb.

The immunohistochemical characteristics of the human olfactory system were (OMP). OMP was detected in the olfactory receptor neurons and processes extending from the olfactory neuroepithelium to the olfactory bulb. The olfactory receptor cells located close to the epithelial surface also contained OMP. In severely degenerate regions, only a few OMP-containing cells were observed. Differences in OMP-staining intensity were noted among the olfactory receptor cells. The thick neuroepithelium. Proliferating olfactory neuroepithelium contained OMP reactive and nonreactive olfactory receptor cells. The presence of OMP reactive and nonreactive olfactory neurons indicates the coexistence of two functionally different phases of olfactory neurons. These findings suggest that continuous cell turnover is occurring in human olfactory neuroepithelium.

Adult↗