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PubMed1992

Neural cell adhesion molecules are present in the fetal human primary olfactory pathway.

Olfactory tissues from human fetuses (17.5-28 weeks of gestation) were stained by immunofluorescence for neural cell adhesion molecules (N-CAMs). Staining for N-CAMs was most prominent in the olfactory nerve bundles in the lamina propria, while in the olfactory epithelium, it was present on the olfactory receptor neurons and globose basal cells. The basal cells proper and supporting cells lacked N-CAMs. In the olfactory bulb, only the olfactory nerve and glomerular layers showed moderate labeling for N-CAMs. Western blot analysis showed that the N-CAMs of the fetal human primary olfactory pathway consisted of three molecular isoforms, N-CAM180, N-CAM140 and N-CAM120.

Cell Adhesion Molecules, Neuronal↗
PubMed1990

Glutamic-acid-decarboxylase-and parvalbumin-like-immunoreactive structures in the olfactory bulb of the human adult.

This study examines the distribution and morphological characteristics of glutamic-acid-decarboxylase-like (GAD)- and parvalbumin-like (PA)-immunoreactive structures in the olfactory bulb of the human adult. GAD-immunoreactive somata occurred in the glomerular layer, the external granule cell layer, the more superficial portion of the external plexiform layer, and the internal granule cell layer. The cells were small- to medium-sized. Demonstration of lipofuscin pigment revealed the presence of unpigmented as well as pigmented neurons, thus suggesting the existence of two subpopulations of GAD-positive neurons. GAD-immunoreactive puncta and/or fibers were mainly seen in the periglomerular region and the internal granule cell layer. All other layers of the bulb, as well as the intrabulbar portion of the anterior olfactory nucleus, displayed considerably less of these puncta and/or fibers. The olfactory nerve layer remained practically clear of immunoreactive material. PA-immunoreactive somata occurred in the glomerular layer and both the external and internal granule cell layer. Only a small number of immunoreactive nerve cells were encountered within the white matter or the olfactory tract. Most PA-positive neurons displayed characteristics of short axon cells whereas a few others resembled van Gehuchten cells. All of the PA-immunoreactive neurons were devoid of lipofuscin pigment. Immunoreactive puncta and fibers were present in all layers though predominating in the periglomerular region, the olfactory nerve layer, and the internal granule cell layer. The intrabulbar portions of the anterior olfactory nucleus did not show any immunoreactive structures.

Adult↗
PubMed2001

Cellular interactions in the development of the olfactory system: an ablation and homotypic transplantation analysis.

In the current study, we addressed two questions: First, is the olfactory placode necessary for the development of the olfactory bulb and the entire telencephalon? Second, does the olfactory placode contribute cells to the olfactory bulb? We addressed these questions by unilaterally ablating the olfactory placode in chick embryos before an olfactory nerve was produced and, in a second series of experiments, by replacing the ablated chick olfactory placode with a quail olfactory placode. Our results indicate that the olfactory placode is critical for olfactory bulb development, but is not necessary for the development of the rest of the telencephalon. Further, our results support the hypothesis that LHRH neurons and olfactory nerve glia originate in the olfactory placode, but do not support an olfactory placodal origin for other cell types within the olfactory bulb.

Animals↗
PubMed2003

In vitro and in vivo characterization of a novel semaphorin 3A inhibitor, SM-216289 or xanthofulvin.

SM-216289 (xanthofulvin) isolated from the fermentation broth of a fungal strain, Penicillium sp. SPF-3059, was identified as a strong semaphorin 3A (Sema3A) inhibitor. Sema3A-induced growth cone collapse of dorsal root ganglion neurons in vitro was completely abolished in the presence of SM-216289 at levels less than 2 mum (IC50 = 0.16 mum). When dorsal root ganglion explants were co-cultured with Sema3A-producing COS7 cells in a collagen gel matrix, SM-216289 enabled neurites to grow toward the COS7 cells. SM-216289 diminished the binding of Sema3A to its receptor neuropilin-1 in vitro, suggesting a direct interference of receptor-ligand association. Moreover, our data suggest that SM-216289 interacted with Sema3A directly and blocked the binding of Sema3A to its receptor. We examined the efficacy of SM-216289 in vivo using a rat olfactory nerve axotomy model, in which strong Sema3A induction has been reported around regenerating axons. The regeneration of olfactory nerves was significantly accelerated by a local administration of SM-216289 in the lesion site, suggesting the involvement of Sema3A in neural regeneration as an inhibitory factor. SM-216289 is an excellent molecular probe to investigate the function of Sema3A, in vitro and in vivo, and may be useful for the treatment of traumatic neural injuries.

Animals↗
PubMed1998

ErbB-3 and ErbB-4 expression in the mouse olfactory system.

The interplay between neuregulins and the ErbB receptor family has a pivotal role in the development of several tissues, including the nervous system, and is maintained in the adult olfactory system where extensive plasticity and neurogenesis are retained. In the present work we show the immunohistochemical localization of ErbB-3 and ErbB-4 in the olfactory system of adult normal and lesioned mice. The expression of ErbB-3 is demonstrated to be restricted to the ensheathing cells of the olfactory nerve and to a few substentacular cells of the olfactory epithelium (OE). ErbB-3 staining circumvents the glomeruli but is never observed inside them or elsewhere in the adult olfactory bulb. Conversely, ErbB-4 immunoreactivity is found in all the periglomerular and mitral/tufted cells of the olfactory bulb (OB) and to a minor extent in the olfactory neurons and basal cells of the OE. Interestingly enough, cells coming out from the rostral migratory stream of the subependymal layer (SEL), as well as isolated cells in the granule cell layer, possibly migrating cells, strongly stained for ErbB-4 expression. Lesions of the olfactory epithelium have been performed by unilateral intranasal irrigation with ZnSO4 and 3 weeks after the irrigation, the olfactory bulbs were analyzed for olfactory marker protein (OMP), tyrosine hydroxylase (TH), ErbB-3 and ErbB-4 expression. In the deafferented OB, the drastic loss of immunoreactivity for OMP was accompanied by a strong reduction of ErbB-3 expression. Most of the deafferented dopaminergic interneurons switched off TH expression. In the deafferented periglomerular and mitral/tufted cells ErbB-4 expression was turned off and down, respectively. No differences were noted at the granular cell layer level in the deafferented OB with respect to control. Taken together our results suggest that, in normal conditions, neuregulins are involved in the survival of the ensheathing cells of the olfactory nerve through ErbB-3 activation and in the functional activity of postsynaptic neurons through ErbB-4 activation.

Animals↗
PubMed1994

[Abnormal tau protein expression in biopsied human olfactory mucosa].

Abnormal tau protein expression was immunohistochemically examined in biopsied human olfactory mucosa. The olfactory mucosa of 25 patients with olfactory disturbances, whose structures were relatively preserved, was immunostained with a polyclonal antibody derived from neurofibrillary tangles from the brains of patients with Alzheimer's disease. Abnormal tau protein immunoreactivity was found in the olfactory vesicles, dendrites and perikarya of the olfactory receptor cells in the epithelium and olfactory nerve bundles in the lamina propria. This immunoreactivity in the olfactory nerve bundles was observed in patients in their teens to 80's, and the immunoreactivity of the olfactory vesicles and dendrites of the olfactory receptor cells was widely distributed in patients in their 30's to 70's. On the other hand, the immunoreactivity of the perikarya of the olfactory receptor cells was observed only in patients in their 50's and 60's. These results indicate that abnormal tau protein accumulation of perikarya is a pathological change and is related to aging of the olfactory neurons.

Adolescent↗
PubMed1992

The influence of the olfactory placode on the development of the telencephalon in Xenopus laevis.

Removal of the sensory plate in Xenopus laevis embryos was performed to study the influence of the olfactory anlage on the development of the forebrain. Embryos, which at stage 22-23 underwent removal of the olfactory anlagen, were killed from stage 47 to 60. In 79% of the animals, two olfactory organs reformed and gave origin to two olfactory nerves which contacted the forebrain. In this instance, the telencephalic hemispheres developed normally. In 14% of the animals, one olfactory organ reformed which contacted the brain by means of one olfactory nerve. This resulted in the development of a unique, reduced in size, cone-shaped telencephalic lobe. In the remaining animals, only a rudiment of the olfactory organ, unconnected with the brain, was present; in these cases, the telencephalon did not develop. Similar results were observed in embryos where olfactory anlagen removal was coupled with damage to, or partial removal of, the prosencephalic vesicle. In animals where lesion of the forebrain was performed without placodal removal, normal development of the forebrain was observed. The developmental relationship observed between the olfactory organ and the forebrain suggests an active role of the nose on the development of the brain.

Animals↗
PubMed1999

Gender effects on odor-stimulated functional magnetic resonance imaging.

On standardized tests of odor identification and odor detection, women tend to score better than men at nearly all age groups. We sought to determine if these findings would translate to differences between the sexes in the volume of activated brain when odors are presented to subjects as the stimulants for functional magnetic resonance imaging (FMRI) experiments. The activation maps of eight right-handed women (mean age 25.3 years old, range 20-44, S.D. 8.3 years) were compared with those of 8 right-handed men (mean age 30.5, range 18-37, S.D. 6.5 years) given the same olfactory nerve stimuli in an FMRI experiment at 1.5 T. Olfactory stimuli were delivered to the patients in a passive fashion using a Burghart OM4-B olfactometer with a nose piece inserted into the patients' nostrils. We used agents (eugenol, phenyl ethyl alcohol, or phenyl ethyl alcohol alternating with hydrogen sulfide) that were selective for olfactory nerve stimulation in the nose. The odorants were delivered to both nostrils for 1 s every 4 s during a 30 s 'on-period'. During the 30 s 'off-period', the patient received room air at the same flow rate. The women's group-averaged activation maps showed up to eight times more activated voxels than men for specific regions of the brain (frontal and perisylvian regions). The left and right inferior frontal regions showed a statistically significant increase in activation in women at p<0.01. In general, more women showed activation than men. The results suggest that (1) FMRI activation maps in subject groups can demonstrate correlates to psychophysical tests of olfaction, and (2) one must control for gender when performing odor-stimulated FMRI experiments.

Adolescent↗
PubMed1993

Organization of inhibition in the rat olfactory bulb external plexiform layer.

1. Intracellular recordings were made from the output neurons (mitral and tufted cells) of the rat olfactory bulb during electrical orthodromic stimulation of the olfactory nerve layer (ONL) and antidromic stimulation of the lateral olfactory tract and posterior piriform cortex (pPC) to test for physiological differences among the neuron types. Many of these neurons were identified by intracellular injections of biocytin, and others were identified by their pattern of antidromic activation. 2. Both marked and unmarked mitral cells showed large inhibitory postsynaptic potentials (IPSPs) in response to antidromic stimulation of the pPC, whereas tufted cells exhibited small IPSPs in response to pPC stimulation. Tufted cells, however, showed large IPSPs in response to ONL stimulation. In many cases, these tufted cell responses to ONL stimulation were larger than the mitral cell responses. The marked superficial tufted cells, those with basal dendrites in the superficial sublayer of the external plexiform layer (EPL), had the smallest IPSPs in response to pPC stimulation. These data support anatomic observations suggesting that the granule cell populations responsible for the IPSPs may be different for mitral and for superficial tufted cells. 3. The different types of output cells also showed differences in their responses to orthodromic stimulation. Type I mitral cells, which have basal dendrites confined to the deep sublayer of the EPL, were significantly less excitable by ONL stimulation than were the type II mitral cells, which have basal dendrites distributed within the intermediate sublayer of the EPL. Half of the type I mitral cells could not be excited at all by ONL stimulation. Superficial tufted cells showed even greater orthodromic excitability than type II mitral cells, usually responding to ONL stimulation with two or more spikes. 4. The ionic basis of the IPSPs in the superficial tufted cells appeared similar to those described for mitral cells. These IPSPs could be reversed by chloride injection and were associated with increased membrane conductance. 5. For both mitral and tufted cells, the number of ONL electrodes evoking IPSPs was greater than the number evoking spikes. These data suggest a kind of center-surround organization of inputs to these cells from the ONL, although this does not yet imply that the sensory receptive field of these output cells has a center-surround organization. 6. In conclusion, the properties of rat olfactory bulb output cells correlate with the sublayers of the EPL in which their basal dendrites lie.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2005

Activation of noradrenergic transmission by alpha2-adrenoceptor antagonists counteracts deafferentation-induced neuronal death and cell proliferation in the adult mouse olfactory bulb.

The olfactory bulb is the target of neural progenitor cells that are generated in the subventricular zone of the lateral ventricle in the adult brain. This permanent neurogenesis is likely influenced by olfactory input to the bulb since previous studies have shown that cell proliferation and/or apoptotic death are stimulated by naris closure or surgical transection of the olfactory nerve. Since the olfactory bulb is densely innervated by noradrenergic afferents originating in the locus coeruleus, we have studied the impact of pharmacologically activating this noradrenergic system on cell death and proliferation following unilateral olfactory axotomy in the adult mouse olfactory bulb. We found that noradrenaline release in the olfactory bulb was significantly increased by intraperitoneal injections of the selective alpha(2)-adrenoceptor antagonists, dexefaroxan (0.63 mg/kg) and 5-fluoro-methoxyidazoxan (F 14413; 0.16 mg/kg). A chronic treatment with either compound for 7 days following olfactory axotomy significantly reduced neuronal death, glial activation and cell proliferation in the deafferented olfactory bulb. These data (1) confirm that alpha(2)-adrenoceptor antagonists, presumably by facilitating central noradrenergic transmission, afford neuroprotection in vivo, as previously shown in models of cerebral ischemia, excitotoxicity and devascularization-induced neurodegeneration, and (2) support a role of the locus coeruleus noradrenergic system in promoting survival of neurons in areas of the brain where neurogenesis persists in the adult.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed2005

Detecting activity in olfactory bulb glomeruli with astrocyte recording.

In the olfactory bulb, axons of olfactory sensory neurons (OSNs) expressing the same olfactory receptor converge on specific glomeruli. These afferents form axodendritic synapses with mitral/tufted and periglomerular cell dendrites, whereas the dendrites of mitral/tufted cells and periglomerular interneurons form dendrodendritic synapses. The two types of intraglomerular synapses appear to be spatially isolated in subcompartments delineated by astrocyte processes. Because each astrocyte sends processes into a single glomerulus, we used astrocyte recording as an intraglomerular detector of neuronal activity. In glomerular astrocytes, a single shock in the olfactory nerve layer evoked a prolonged inward current, the major part of which was attributable to a barium-sensitive potassium current. The K+ current closely reflected the time course of depolarization of mitral/tufted cells, indicating that K+ accumulation mainly reflects the activity of mitral/tufted cells. The astrocyte K+ current was dependent on AMPA and NMDA receptors in mitral/tufted cells as well as on a previously undescribed metabotropic glutamate receptor 1 component. Block of the K+ current with barium unmasked a synaptic glutamate transporter current. Perhaps surprisingly, the transporter current had components caused by glutamate released at both olfactory nerve terminals and mitral/tufted cell dendrites. The time course of the transporter currents suggested that rapid synchronous glutamate release at OSN terminals triggers asynchronous glutamate release from mitral/tufted cells. Glomerular astrocyte recording provides a sensitive means to examine functional compartmentalization within and between olfactory bulb glomeruli.

Animals↗
PubMed1997

Experimental infection of swine and cat central nervous systems by the pig paramyxovirus of the blue eye disease.

This study analyses whether the pig paramyxovirus of blue eye disease (PPBED) infects the central nervous system (CNS) utilizing anterograde and retrograde peripheral nerve transport systems. The virus was injected into muscle and skin, and inoculated per nasum. The presence of PPBED was detected by an immunohistochemical method using polyclonal mouse antibodies against the whole inactivated virus, and was revealed with polyclonal rabbit antibodies against mouse immunoglobulin G (IgG) labelled with peroxidase. The PPBED injected into the pig medial gastrocnemius (MG) muscle was detected in a terminal branch innervating the MG muscle, in neural fibres of the sciatic nerve, in fibres of the ventral and dorsal spinal roots and in ventral horn neurones of the spinal cord. When PPBED was injected into the skin area innervated by the sural nerve, it was detected in neural fibres of the sural and sciatic nerves and in spinal cord dorsal horn neurones. The per nasum inoculum rapidly invaded the CNS through the olfactory nerve. The study concluded that, in order to invade the CNS, PPBED was transported retrogradely by peripheral cutaneous and muscular nerves, and anterogradely by the olfactory nerve. No PPBED was detected in either cat peripheral nerves or in cat CNS.

Animals↗
PubMed1984

Synaptic excitatory and inhibitory interactions at distal dendritic sites on mitral cells in the isolated turtle olfactory bulb.

The olfactory nerves terminate exclusively on the distal dendritic tufts of mitral cells in the olfactory bulb, which makes this a favorable model for analysis of synaptic responses in distal dendrites. Intracellular recordings of responses to olfactory nerve volleys have been obtained in the isolated turtle olfactory bulb. Single mitral cells usually responded with excitatory postsynaptic potentials (EPSPs) to volleys in two different bundles, indicating convergence from separate receptor neuron populations. Paired volleys revealed long-lasting inhibition of a test EPSP by a conditioning volley. This could be shown to be independent of the inhibition of mitral cells by granule cell interneurons in the deeper layers. The results suggest that excitatory and inhibitory synaptic interactions in the glomerular layer are important in the processing of olfactory inputs. The results also provide an exception to the classical doctrine that synaptic inhibition is preferentially sited near the cell body and axon hillock in order to control impulse generation there. Our findings of inhibitory actions on distal dendrites of mitral cells may provide a model for similar actions on distal dendrites of other central neurons.

Animals↗
PubMed1997

Role of laminin in axonal extension from olfactory receptor cells.

The role of laminin, an extracellular matrix molecule believed to be involved in axon extension, was explored in the outgrowth of olfactory receptor cells and therefore in the maintenance of organization in the olfactory pathway. First, immunocytochemistry was used to examine laminin expression in the olfactory nerve and bulb during development. Laminin immunoreactivity was high in the olfactory nerve and glomerular layers. Although it declined in intensity, laminin expression continued in the nerve and in single glomeruli of adults. Second, the influence of laminin on neurite outgrowth was examined in vitro using olfactory receptor cells harvested from E14 rat embryos. We developed an in vitro assay to quantify the substrate preference of outgrowing neurites. Cells were cultured for 48 h on coverslips coated with either poly-L-lysine alone, or poly-L-lysine overlaid with laminin. On laminin-coated regions of coverslips, the primary neurites of olfactory receptor cells were 52% longer than on the poly-L-lysine control substrates. In addition, the direction of the neurite outgrowth was influenced by laminin. Fifty-six percent of all receptor cells located in a defined area surrounding a laminin zone extended neurites onto laminin. In contrast, only 7% of all receptor cells located in the corresponding laminin zone extended a neurite onto poly-L-lysine. In summary, these data suggest that laminin provides a favorable substrate for the extension of the primary neurite from olfactory receptor cells and the direction of their extension. Therefore, laminin may be a factor underlying continuous olfactory receptor cell axon outgrowth and its pathfinding in the olfactory system.

Animals↗
PubMed1991

Localization of tyrosine hydroxylase and olfactory marker protein immunoreactivities in the human and macaque olfactory bulb.

These studies utilized specific antisera to examine the distribution and characteristics of tyrosine hydroxylase and olfactory marker protein in the olfactory bulb of the human and macaque monkey. The macaque displayed immunoreactive profiles to both antisera comparable to those described previously for other mammals. Olfactory marker protein antiserum labeled the olfactory nerve layer and glomeruli. Within the glomeruli, labeled processes were interdigitated with unlabeled processes believed to be the postsynaptic dendrites of olfactory bulb neurons. Tyrosine hydroxylase antisera labeled somata surrounding the glomeruli as well as putative dendritic processes with the glomerular neuropil. It appeared that only a subset of juxtaglomerular neurons were immunoreactive. A similar pattern was observed in the human for both antibodies. Fascicles of olfactory marker protein immunoreactive olfactory nerves often coursed long distances into the olfactory bulb prior to arborizing within a glomerulus. The data suggest that olfactory receptor cell axons destined for specific glomeruli fasciculate into bundles prior to reaching the target glomeruli. The immunoreactivity in the human to tyrosine hydroxylase was qualitatively similar to the macaque and other mammals although the number of labeled somata and intraglomerular processes appeared lower. As in the macaque, it appeared that only a subset of juxtaglomerular neurons were labeled.

Adult↗
PubMed1993

High-affinity cAMP phosphodiesterase and adenosine localized in sensory organs.

Odorant-stimulated formation of cAMP in olfactory receptor neurons may mediate olfactory signal transduction. The response is short and desensitization occurs rapidly, possibly by induction of cyclic nucleotide phosphodiesterase (PDE) activity. Previously, we showed that two low Km PDEs regulate hydrolysis of cAMP in olfactory cilia. One PDE is Ca2+/calmodulin-dependent and non-selective for both cAMP-PDE and cGMP; the other is Ca2+/calmodulin-independent, sensitive to rolipram and selective for cAMP. We have localized cAMP-selective PDE in olfactory, gustatory and retinal sensory systems by autoradiography with the selective inhibitor [3H]rolipram. We observe dense binding over olfactory neurons, particularly over olfactory nerve bundles and olfactory cilia. In the tongue apical regions of taste buds of the circumvallate papillae are strongly labeled as well as portions of the glossopharyngeal nerve. Retinal binding is most dense over the inner plexiform layer, ganglion cells and the optic nerve but is also substantial over the inner nuclear layer. The pattern of [3H]rolipram-binding in retina is reminiscent of adenosine localization. Accordingly, adenosine was immunohistochemically localized in olfactory, gustatory and retinal tissues. Adenosine immunoreactivity is observed in olfactory neurons, in the basal regions of taste buds and in retinal ganglion cells.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1989

[Olfactory groove meningioma].

Twelve cases of olfactory groove meningioma had been reported. The first symptom of the disease was dysfunction of the olfactory nerve. Rhinologists are responsible for the early diagnosis of the disease. The very important diagnostic points of the disease are dysfunction of the olfactory nerve; visual impairment; headache; Foster-Kennedy's syndrome and the CT scan. The clinical features, diagnosis and treatment of the 12 cases were discussed. Early diagnosis of the diseases is very important for the performance of the operation via the rhino-anterior fossa approach.

Adult↗
PubMed1994

Basal interfalcine approach through a frontal sinusotomy with vein and nerve preservation. Technical note.

The authors describe a new method for a frontal interhemispheric approach when treating craniopharyngiomas of the third ventricle or anterior communicating artery aneurysms. This technique ensures preservation of the bridging veins and the olfactory nerves. This "basal interfalcine approach" involves a craniotomy in the centrobasal portion of the frontal bone (the frontal sinus), removal of the inner tables and the crista galli, and splitting the basal portion of the falx into two leaves, through which the basal interhemispheric fissure is opened. The olfactory nerves are protected by the leaves of the falx, and the bridging veins are preserved because the approach is low enough to spare them. The surgical techniques are described together with a unilateral variation of this approach. The significance of preserving the bridging veins is discussed in connection with avoidance of postoperative contusional hemorrhage.

Cerebral Ventricle Neoplasms↗