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PubMed2006

Alpha-synuclein pathology of the spinal and peripheral autonomic nervous system in neurologically unimpaired elderly subjects.

Studies on cases with incidental Lewy body disease (ILBD) suggest that alpha-synuclein (alphaSN) pathology of Parkinson's disease (PD) starts in lower brainstem nuclei and in the olfactory bulb. However, medullary structures as the induction site of alphaSN pathology have been questioned as large parts of the nervous system, including the spinal cord and the peripheral autonomic nervous system (PANS), have not been examined in ILBD. Thus, the time course of PD lesions in the spinal cord or PANS in relation to medullary lesions remains unknown. We collected 98 post mortem cases with no reference to PD-associated symptoms on clinical records. alphaSN pathology was found in the central nervous system, including the spinal cord, and in the PANS in 17 (17.3%) cases. alphaSN pathology was encountered in autonomic nuclei of the thoracic spinal cord, brainstem and olfactory nerves in 17/17, in sacral parasympathetic nuclei in 15/16, in the myenteric plexus of oesophagus in 14/17, in sympathetic ganglia in 14/17, and in the vagus nerve in 12/16 cases. In addition to the thoracic lateral horns, a high number of alphaSN lesions was also found in non-autonomic spinal cord nuclei. Considering supraspinal structures our cases corresponded roughly to the recently described sequential order of alphaSN involvement in PD. Our study indicates, however, that the autonomic nuclei of the spinal cord and the PANS belong to the most constantly and earliest affected regions next to medullary structures and the olfactory nerves. A larger cohort of ILBD cases will be needed to pinpoint the precise induction site of alphaSN pathology among these structures.

Aged↗
PubMed1994

Luteinizing hormone-releasing hormone (LHRH) and neural cell adhesion molecule (NCAM)-immunoreactivity in development of the forebrain and reproductive system.

The origin and migration of LHRH neurons (detected by immunocytochemical procedures) is preceded by a migration of NCAM-immunoreactive cells from the olfactory epithelium, and the formation of an NCAM-immunoreactive cellular aggregate between the olfactory epithelium and the developing forebrain. The central processes of the olfactory nerves grow into the lateral parts of this aggregate and the terminal and vomeronasal nerves grow into the medial parts. No nerve fibers of the main or accessory olfactory systems grow directly into the forebrain. The LHRH neurons, following the course of the terminal and vomeronasal nerves, traverse the medial edge of the NCAM-immunoreactive cellular aggregate before they enter the medial forebrain caudal to the developing olfactory bulbs. The LHRH neurons do not migrate through the olfactory bulbs. After formation of the olfactory bulbs, the cellular aggregate disappears and is replaced by the olfactory nerve layer of the olfactory bulb. The NCAM and LHRH-immunoreactive cells on the medial side appear to the retained in the ganglion terminale of the terminal nerve. The fate of the NCAM-immunoreactive cells that formed the aggregate could not be determined by the methods used in these studies. The early-appearing NCAM-immunoreactive cells may function to separate and direct axons of the olfactory, vomeronasal and terminal nerves (and the LHRH neurons) to their respective targets in the forebrain. The development and migration of neurons from both the lateral and medial parts of the olfactory placode appears to be essential for the normal development of the forebrain and reproductive system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Glial cells from adult rat olfactory bulb: immunocytochemical properties of pure cultures of ensheathing cells.

Three morphologically and immunohistochemically distinct types of cell were present in primary cultures of adult rat olfactory nerve and glomerular layers of the olfactory bulb. One cell type was multipolar and stained positively for glial fibrillary acidic protein; a second type had fried egg-like morphology and stained with antibodies to epitope ED1; the third cell type had fusiform morphology, reacted with antibodies to vimentin and laminin and was glial fibrillary acidic protein- and ED1-negative. Trypsinization of these primary cultures (3 min, 37 degrees C), detached multipolar and fusiform cells only. When detached cells were set up in secondary culture on a glass substrate, fusiform cells did not attach, resulting in a pure culture of multipolar cells. Multipolar cells were glial fibrillary acidic protein- and myelin basic protein-positive and had the properties of so-called ensheathing cells or Blanes' glia. Immunoreactivity with anti-nerve growth factor receptor and anti-fibronectin allowed us to identify four distinct populations of multipolar ensheathing cells. One population was nerve growth factor receptor-positive, fibronectin-negative. A second was nerve growth factor receptor-negative and fibronectin-positive. A third was positive for both markers and the remaining cells did not stain for either of them. The morphological and immunological characteristics of cultured cells from olfactory nerve and glomerular layers were similar to those of Schwann cells and the similarities could account for the permissivity to axonal growth of the olfactory bulb.

Animals↗
PubMed1977

Physiological and anatomical characteristics of reticulospinalneurones in lamprey.

1. Intracellular records were obtained from giant reticulospinal cells (Müller cells) in the brain of adult lamprey. The cells had maximum resting potentials of -80 mV and action potentials with overshoots of 30 mV. Input resistances varied from 2 to 8 MOmega.2. Individual spontaneous excitatory and inhibitory synaptic potentials (e.p.s.p.s and i.p.s.p.s) were observed, as well as occasional high frequency bursts of excitatory potentials. Much of the spontaneous synaptic activity could be eliminated by elevating the Ca(2+) concentration in the bathing solution to 10-15 mM, suggesting that the synaptic potentials were due to spike activity in elements presynaptic to Müller cells.3. Electrical stimulation of cranial nerves produced synaptic responses in Müller cells. Ipsilateral vestibular nerve stimulation produced i.p.s.p.s; contralateral stimulation, e.p.s.p.s. Stimulation of either optic nerve produced mixed synaptic responses with e.p.s.p.s dominating in cells with large resting potentials. Trigeminal nerve stimulation produced mixed responses. Olfactory nerve stimulation produced excitation. Spinal cord stimulation produced e.p.s.p.s and i.p.s.p.s, the dominant effect being inhibition.4. In favourable preparations strong electrical stimulation of cranial nerves produced afterdisharges in Müller cells, lasting from a few seconds after stimulation of the olfactory and vestibular nerves to as long as several minutes after optic, trigeminal or spinal cord stimulation.5. Natural stimulation of tactile, visual and vestibular receptors resulted in synaptic responses similar to those produced by electrical stimulation of the cranial nerves. Fish odour applied to the olfactory mucosa produced no response.6. Iontophoretic application of L-glutamate to Müller cells produced depolarization accompanied by a decrease in input resistance. In addition, glutamate produced bursts of inhibitory and excitatory synaptic potentials, presumably by depolarizing excitatory or inhibitory nerve terminals or nearby cell bodies.7. Iontophoretic application of gamma-aminobutyric acid (GABA) resulted in a slight hyperpolarization, accompanied by a large reduction in input resistance. The reversal point both of the hyperpolarizations and of the spontaneous inhibitory post-synaptic potentials was about 6 mV greater than the resting potential.8. There were two types of synaptic ending on Müller cell bodies, one type containing round vesicles and the other containing ellipsoidal vesicles. These terminals were intermixed over the surface of the cell bodies and dendrites with no readily apparent segregation.9. Intracellular records from the spinal axons of Müller cells during electrical stimulation of cranial nerves and spinal cord showed, in addition to the normal propagating action potential activity which normally originates in the cell bodies, depolarizing, hyperpolarizing and biphasic evoked potentials. These membrane responses were grossly similar in appearance to synaptic potentials except that the large depolarizing potentials had unusually long decay times. The physiological basis of these potentials remains unclear.10. Electron microscopic examination showed very few synaptic endings afferent to Müller axons, a finding in contrast to the abundance of synaptic-like potentials recorded. However, the occasional synapses afferent to Müller axons were invariably located near an efferent synaptic region of the axon itself. This raises the possibility that a very limited number of synaptic regions of Müller axons may be subject to presynaptic modulation of transmitter release.11. The observations reported here support the idea that Müller cells in lamprey are an important motor outflow from the brain and serve to coordinate the lamprey's trunk responses to external sensory stimulation.

Action Potentials↗
PubMed1990

Intracellular responses of identified rat olfactory bulb interneurons to electrical and odor stimulation.

1. Intracellular recordings were made from 28 granule cells and 6 periglomerular cells of the rat olfactory bulb during odor stimulation and electrical stimulation of the olfactory nerve layer (ONL) and lateral olfactory tract (LOT). Neurons were identified by injection of horseradish peroxidase (HRP) or biocytin and/or intracellular response characteristics. Odorants were presented in a cyclic sniff paradigm, as reported previously. 2. All interneurons could be activated from a wide number of stimulation sites on the ONL, with distances exceeding their known dendritic spreads and the dispersion of nerve fibers within the ONL, indicating that multisynaptic pathways must also exist at the glomerular region. All types of interneurons also responded to odorant stimulation, showing a variety of responses. 3. Granule cells responded to electrical stimulation of the LOT and ONL as reported previously. However, intracellular potential, excitability, and conductance analysis suggested that the mitral cell-mediated excitatory postsynaptic potential (EPSP) is followed by a long inhibitory postsynaptic potential (IPSP). An early negative potential, before the EPSP, was also observed in every granule cell and correlated with component I of the extracellular LOT-induced field potential. We have interpreted this negativity as a "field effect," that may be diagnostic of granule cells. 4. Most granule cells exhibited excitatory responses to odorant stimulation. Odors could produce spiking responses that were either nonhabituating (response to every sniff) or rapidly habituating (response to first sniff only). Other granule cells, while spiking to electrical stimulation, showed depolarizations that did not evoke spikes to odor stimulation. These depolarizations were transient with each sniff or sustained across a series of sniffs. These physiological differences to odor stimulation correlated with granule cell position beneath the mitral cell layer for 12 cells, suggesting that morphological subtypes of granule cells may show physiological differences. Some features of the granule cell odor responses seem to correlate with some of the features we have observed in mitral/tufted cell intracellular recordings. Only one cell showed inhibition to odors. 5. Periglomerular (PG) cells showed a response to ONL stimulation that was unlike that found in other olfactory bulb neurons. There was a long-duration hyperpolarization after a spike and large depolarization or burst of spikes (20-30 ms in duration). Odor stimulation produced simple bursts of action potentials, Odor stimulation produced simple bursts of action potentials, suggesting that PG cells may simply follow input from the olfactory nerve.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Differential distribution of six calcium-binding proteins in the rat olfactory epithelium during postnatal development and adulthood.

Odorant stimulation of receptor cells results in a calcium influx that activates the transduction pathway. Ca2+ acceptors, such as calmodulin, may mediate between the change in intracellular calcium and the conductance mechanism underlying the initial electrical event. Ca2+ acceptors also may participate in subsequent processing of olfactory information. The identification and characterization of these molecules, therefore, should provide important information about the complex signal transduction pathway involving calcium in olfaction as well as other sensory systems. The present study describes the distribution of six calcium-binding proteins in the rat main olfactory epithelium during postnatal development to determine when different Ca2+ acceptors can be detected and whether they segregate into different layers or portions of the epithelium. Calmodulin, calretinin, calbindin-D28k, neurocalcin, and recoverin were detected immunohistochemically in olfactory receptors but not in basal cells. S-100 immunoreactivity was restricted to glial cells primarily around the cribriform plate. During postnatal development (from P1 to P20), calmodulin, calretinin, calbindin-D28k, and neurocalcin formed a gradient of immunoreactivity descending from the central to the lateral areas in the nasal cavity, whereas recoverin was expressed only in sporadic, mature receptors in the proximal region of the mucosa. At P20, the immunoreactivity pattern for each calcium-binding protein was identical to the adult profile, indicating that the olfactory epithelium had reached maturity by this stage. Olfactory nerve fiber bundles displayed a differential staining pattern from P1 until adulthood for calbindin-D28k and calretinin (internal portions of bundles). Differential calmodulin immunoreactivity of olfactory nerves (large external portions of bundles) appeared at P10. The immunoreactivity of the nerve fiber bundles may reflect a further degree of organization relevant to odor discrimination.

Animals↗
PubMed2000

Smell and taste in children with simple obesity.

In 30 children, aged 10-16 years and suffering from simple obesity, significantly lowered odour detection thresholds were noted. The thresholds were lower than the average for a given age group in around 20% of obese children in cases of odours stimulating olfactory nerve and in around 57% in cases of substances stimulating olfactory and trigeminal nerves. Odour identification thresholds were similarly affected, with identification of olfactory nerve plus trigeminal nerve stimulating odours affected more than twice as frequently. In 77% cases also the electrogustometric thresholds were found below the normal range values when anode was used as the stimulating electrode. The detected alterations may be linked to metabolic disturbances, which accompany simple obesity.

Adolescent↗
PubMed1990

Expression of the neuronal surface glycoprotein Thy-1 is under post-transcriptional control, and is spatially regulated, in the developing olfactory system.

Expression of the neuronal cell surface glycoprotein Thy-1 has been studied during the development of the olfactory bulb in mice and rats, using in situ hybridisation and immunohistochemistry to follow the appearance of Thy-1 mRNA and protein, respectively. The mRNA was first detected 4 days before birth on all mitral cells, the main projection neuron of the bulb, as they formed a distinct layer and grew dendrites. At no stage was any spatial gradient of expression of Thy-1 mRNA evident around the mitral cell layer. Thy-1 protein, on the other hand, was first detectable 2 days later on a group of mitral cells immediately adjacent the point of entry of the olfactory nerve. The numbers of immunoreactive cells spread, over the next 7 days, to include all mitral cells, those located rostrally and laterally in the bulb being slowest to express Thy-1 protein. Thus there was a spatiotemporal gradient of expression of Thy-1 protein, which was not apparent in the earlier general expression of its mRNA, suggesting that some further inductive signal was required after transcription in order to get effective production of protein. Analysis of the growth of the mitral cell axons in the lateral olfactory tract suggested this signal was related to the cessation of axonogenesis, as Thy-1 immunoreactivity became detectable on these axons only when their expression of the transient epitope detected by the G10 antibody, present on microtubule-associated protein (MAP)1x only during axonal growth, declined. For the first week after Thy-1 protein appeared on mitral cells, it was not distributed uniformally on their surface. Immunoreaction was relatively weak on the somatic surface, and the molecule appeared to be entirely excluded from the distal regions of its main dendrite, above the outer plexiform layer. Here the dendrite reaches up to the synaptic glomeruli formed with the incoming olfactory nerve axons. These distal regions of the dendritic shaft became immunoreactive only after the periglomerular cells had first begun to express Thy-1 protein in the glomeruli. Immunolabelling of the somatic membrane then increased, to give the adult pattern of uniform Thy-1 labelling of the neuronal membrane by the end of the second postnatal week. It is suggested that some of the molecular features of Thy-1, and anatomical features of the main bulb, could interact to produce this initial restriction of Thy-1 to particular parts of the mitral cell surface.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2006

Dendritic excitability and calcium signalling in the mitral cell distal glomerular tuft.

The processing of odour information starts at the level of the olfactory glomerulus, where the mitral cell distal dendritic tuft not only receives olfactory nerve sensory input but also generates dendrodendritic output to form complicated glomerular synaptic circuits. Analysing the membrane properties and calcium signalling mechanisms in these tiny dendritic branches is crucial for understanding how the glomerular tuft transmits and processes olfactory signals. With the use of two-photon Ca2+ imaging in rat olfactory bulb slices, we found that these distal dendritic branches displayed a significantly larger Ca2+ signal than the soma and primary dendrite trunk. A back-propagating action potential was able to trigger a Ca2+ increase throughout the entire glomerular tuft, indicative of the presence of voltage-gated Ca2+ conductances in all branches at different levels of ramification. In response to a train of action potentials evoked at 60 Hz from the soma, the tuft Ca2+ signal increased linearly with the number of action potentials, suggesting that these glomerular branches were able to support repetitive penetration of Na+ action potentials. When a strong olfactory nerve excitatory input was paired with an inhibition from mitral cell basal dendrites, a small spike-like fast prepotential was revealed at both the soma and distal primary dendrite trunk. Corresponding to this fast prepotential was a Ca2+ increase confined locally within the glomerular tuft. In summary, the mitral cell distal dendritic tuft possesses both Na+ and Ca2+ voltage-dependent conductances which can mediate glomerular Ca2+ responsiveness critical for dendrodendritic output and synaptic plasticity.

Action Potentials↗
PubMed2002

Cell surface carbohydrates reveal heterogeneity in olfactory receptor cell axons in the mouse.

Cell surface carbohydrates, both in the olfactory system and elsewhere, have been proposed to play critical roles in axon guidance and targeting. Recent studies have used plant lectins to study the heterogeneous distribution of carbohydrates in the olfactory system. One lectin, Dolichos biflorus agglutinin (DBA), heterogeneously labels subsets of glomeruli. In the olfactory epithelium DBA labeled a subset of olfactory sensory neurons (OSNs) including their cilia, dendrites, and somata. OSN axons were also labeled and readily observed in the olfactory nerve and bulb. The patterns of glomerular innervation by DBA labeled (DBA(+)) axons were diverse; some glomeruli contained many labeled axons, while others contained few or no labeled axons. To characterize the heterogeneous innervation of glomeruli, we double labeled olfactory bulbs with DBA and an antibody to olfactory marker protein (OMP). OMP colocalized in most, but not all, DBA(+) axons. To determine if those axons that did not express OMP were immature, we double labeled olfactory bulbs with DBA and anti-GAP-43. GAP-43 rarely colocalized with DBA, suggesting that DBA(+) axons are not, as a population, immature. Triple labeling with all three markers revealed a small subset of DBA(+) axons which did not express either OMP or GAP-43. Electron microscopy established that DBA labels axons in the olfactory nerve and DBA-labeled axons form typical glomerular axodendritic synapses.

Animals↗
PubMed2005

Olfactory and sensory attributes of the nose.

The human nasal cavity contains multiple sensory and olfactory structures. The nasal mucosa with its complex innervation detects the danger substances in the air and stimulates the protective reflexes. Healthy olfactory mucosa allows for appreciation of pleasant aromas and food flavors. The olfactory nerve, in concert with the trigeminal nerve, serves as a main interpreter and modulator of chemosensory information. The anatomy of the olfactory neuroepithelium, which occupies only a small portion of the nasal mucosa, is generally well understood, while the presence and distribution of the sensory/tactile receptors in the mucosa of the nasal cavity is still a subject of controversy. The nasal vestibule, lined with skin, contains receptors that can sense noxious stimuli and air-flow. The sensitivity of the nasal mucosa to air-flow still needs further research. Understanding the distribution of the air-flow receptors could help to guide nasal surgery for obstruction.

Chemoreceptor Cells↗
PubMed1999

Mohr syndrome in two sisters: prenatal diagnosis in a 22-week-old fetus with post-mortem findings in both.

Oral-facial digital syndrome type II (OFP syndrome II; orofaciodigital syndrome II) is a rare autosomal recessive syndrome, first described by Mohr (1941). We present two sisters with Mohr syndrome from a consanguineous family. One is a three-day-old female patient, the other is 22-week-old fetus. Polydactyly with bifid thumbs in both hands, bilateral polysyndactyly of halluces, lateral polysyndactyly and bilateral pes equinovarus were demonstrated in the fetus sonographically. Corpus callosum agenesis, congenital heart disease, bilateral bifid thumbs and halluces and polydactyly were seen in both patients. In addition, post-mortem findings showed absence of olfactory nerve, single atrium. VSD, abnormal lung lobulation and natal teeth in the fetus. Absence of olfactory nerve and natal teeth have not been reported previously in Mohr syndrome.

Autopsy↗
PubMed1986

Laminar organization of the main olfactory bulb of Podarcis hispanica: an electron microscopic and Golgi study.

In this study, the lamination pattern of the main olfactory bulb (MOB) of P. hispanica has been described using EM and Golgi-impregnation techniques. Six layers could be distinguished from the external surface to the ventricles: olfactory nerve layer (ONL), glomerular layer (GL), external plexiform layer (EPL), mitral layer (ML), internal plexiform layer (IPL), and granular cell layer (GCL). In ONL unmyelinated axonic bundles from the olfactory mucosa are seen. The GL is defined by the presence of terminal ramifications of the mitral primary dendrites and by axonic terminals of the olfactory nerve. The EPL is a dendritic articulation layer between the mitral and granule cells, where a great density of dendrodendritic synaptic contacts has been found. The ML is defined by the large mitral cell somata, and the IPL by myelinated axonic bundles that run rostro-caudally. Finally, the GCL is characterized by the presence of granule cells. Using the Golgi-impregnation method, five different neuronal types have been described. In the glomerular layer, a small cell population is located; these neurons seem the periglomerular cells described in mammals. The second type corresponds to the mitral cell population and the morphological features of these cells resemble to those of mammals. The three remaining types constitute the granule cell population; this population is characterized by a great morphological heterogeneousness. However, these types have been differentiated according to their dendritic tree morphology and location of the cell body. A morphological gradient depending on the distance of cell body for each type to the ependymal layer, has been observed. In EM, four different types of neuronal cell bodies according to their location and ultrastructure have been defined. The laminar organization of the MOB of Podarcis is similar to that in all vertebrates. The results for the fine structure and dendritic tree morphology have revealed a high similarity between these reptiles and mammals.

Animals↗
PubMed1984

Functional anatomy of the peripheral olfactory system of the African lungfish Protopterus annectens owen: development of the primary olfactory pathway during postembryonic growth.

Seven specimens of the African lungfish ranging in size from 4 to 350 gm were used for the study of changes in the olfactory nerve and bulb during postembryonic growth as expressed by the increasing number of lamellae of the olfactory organ. Serial semithin sections were used, and the data were studied mathematically. The number of axons of the olfactory nerve, the surface area of the bulb, and the number of mitral cells increase exponentially; the mitral cell density decreases exponentially; and the calculated average convergence (counted axons/counted mitral cells) of axons onto the cells of the bulbar relay increases exponentially. Convergence figures obtained are smaller than those cited by other authors; two factors might explain this: first the mode of calculation, and second the fact that every year this fish undergoes a 6-month starvation stage marked by degeneration of the primary olfactory structure. A preliminary view of the primary olfactory pathway using serial-section reconstructions is proposed: An orderly projection of the mucosa onto the bulb takes place after a 90 degrees rotation of the system of two perpendicular axes which apply to both the olfactory organ and the olfactory bulb. This study suggests an original attempt at relating the postembryonic change in convergence and projection to the primary processing of the olfactory message.

Animals↗
PubMed1976

Fine structure of the olfactory bulb in the goldfish, Carassius auratus.

Ultrastructural studies have aided in identifying the principal cell types and the layers of the olfactory bulb in goldfish. The concentrically arranged four layers are: the primary olfactory nerve layer (most peripheral), the glomerular layer, the mitral cell layer, and the granule cell layer (deepest). Three types of cell bodies were differentiated by their size and cytoplasmic organelles: mitral cells, granule cells and short axon cells. The axons of the primary olfactory nerve formed synaptic contacts with mitral cell dendrites in the glomeruli. Reciprocal synapses were observed between the granule cell dendrites and the mitral cell dendrites in the mitral cell layer. Terminals of the centrifugal fibers forming synaptic contacts with the granule cell dendrites were identified in the granule cell layer. The relationships between the cellular and synaptic organizations and the neural mechanism of olfaction are discussed.

Animals↗
PubMed1975

[Frontobasal cranio-encephalic injuries].

The authors deal with the results accomplished by surgical procedure on 10 cases of fronto-basal trauma. X-Rays taken from the skull disclosed an involvement of bone structures of the fronto-basal region in all cases examined. The most outstanding clinical findings in these cases were: lesion of the olfactory nerve (7cases), bacterial meningitis (3 cases), cerebrospinal fluid cranio-nasal fistula (3 cases). The surgical technic was accomplished according to the procedure devised by Dietz and consisted of plastics of the anterior floor of the skull accompanied by galea-periosteal junction taken out from the scalp. The authors did not find any post-operative complications in the cases registered.

Adolescent↗
PubMed2004

Expression and putative role of lactoseries carbohydrates present on NCAM in the rat primary olfactory pathway.

Primary olfactory neurons project axons from the olfactory neuroepithelium lining the nasal cavity to the olfactory bulb in the brain. These axons grow within large mixed bundles in the olfactory nerve and then sort out into homotypic fascicles in the nerve fiber layer of the olfactory bulb before terminating in topographically fixed glomeruli. Carbohydrates expressed on the cell surface have been implicated in axon sorting within the nerve fiber layer. We have identified two novel subpopulations of primary olfactory neurons that express distinct alpha-extended lactoseries carbohydrates recognised by monoclonal antibodies LA4 and KH10. Both carbohydrate epitopes are present on novel glycoforms of the neural cell adhesion molecule, which we have named NOC-7 and NOC-8. Primary axon fasciculation is disrupted in vitro when interactions between these cell surface lactoseries carbohydrates and their endogenous binding molecules are inhibited by the LA4 and KH10 antibodies or lactosamine sugars. We report the expression of multiple members of the lactoseries binding galectin family in the primary olfactory system. In particular, galectin-3 is expressed by ensheathing cells surrounding nerve fascicles in the submucosa and nerve fiber layer, where it may mediate cross-linking of axons. Galectin-4, -7, and -8 are expressed by the primary olfactory axons as they grow from the nasal cavity to the olfactory bulb. A putative role for NOC-7 and NOC-8 in axon fasciculation and the expression of multiple galectins in the developing olfactory nerve suggest that these molecules may be involved in the formation of this pathway, particularly in the sorting of axons as they converge towards their target.

Amino Sugars↗
PubMed1985

The toxicity of dimethylamine in F-344 rats and B6C3F1 mice following a 1-year inhalation exposure.

Dimethylamine is a widely used commodity chemical, for which there are few chronic toxicity data. Male and female F-344 rats and B6C3F1 mice were exposed by inhalation to 0, 10, 50, or 175 ppm dimethylamine (DMA) for 6 hr/day, 5 days/week for 12 months. Groups of 9-10 male and female rats and mice were necropsied after 6 and 12 months of exposure. No male mice were sacrificed at 12 months due to a high incidence of early deaths in that group. The mean body weight gain of rats and mice exposed to 175 ppm DMA was depressed to approximately 90% of control after 3 weeks of exposure. The only other treatment-related changes were concentration-related lesions in the nasal passages. Two distinct locations in the nose were affected: the respiratory epithelium in the anterior nasal passages, and the olfactory epithelium, especially that lining the anterior dorsal meatus. There was focal destruction of the anterior nasoturbinate and nasal septum, local inflammation, and focal squamous metaplasia of the respiratory epithelium in rats and mice. Mild goblet cell hyperplasia was observed only in rats. The olfactory epithelium exhibited extensive loss of sensory cells with less damage to sustentacular cells. There was also loss of olfactory nerves, hypertrophy of Bowman's glands, and distension of the ducts of these glands by serocellular debris in regions underlying degenerating olfactory epithelium. At the 175-ppm exposure level, rats had more extensive olfactory lesions than mice, with hyperplasia of small basophilic cells adjacent to the basement membrane being present in rats but not mice. After 12 months of exposure to 10 ppm DMA, minimal loss of olfactory sensory cells and their axons in olfactory nerve bundles was observed in the nasal passages of a few rats and mice. These results indicate that the olfactory sensory cell is highly sensitive to the toxic effects of DMA, with minor lesions being produced in rodents even at the current threshold limit value of 10 ppm.

Air Pollutants↗