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Sample records for adult olfactory epithelium

  1. Molecular events in the cell types of the olfactory epithelium during adult neurogenesis

    PubMed Central

    2013-01-01

    Background Adult neurogenesis, fundamental for cellular homeostasis in the mammalian olfactory epithelium, requires major shifts in gene expression to produce mature olfactory sensory neurons (OSNs) from multipotent progenitor cells. To understand these dynamic events requires identifying not only the genes involved but also the cell types that express each gene. Only then can the interrelationships of the encoded proteins reveal the sequences of molecular events that control the plasticity of the adult olfactory epithelium. Results Of 4,057 differentially abundant mRNAs at 5 days after lesion-induced OSN replacement in adult mice, 2,334 were decreased mRNAs expressed by mature OSNs. Of the 1,723 increased mRNAs, many were expressed by cell types other than OSNs and encoded proteins involved in cell proliferation and transcriptional regulation, consistent with increased basal cell proliferation. Others encoded fatty acid metabolism and lysosomal proteins expressed by infiltrating macrophages that help scavenge debris from the apoptosis of mature OSNs. The mRNAs of immature OSNs behaved dichotomously, increasing if they supported early events in OSN differentiation (axon initiation, vesicular trafficking, cytoskeletal organization and focal adhesions) but decreasing if they supported homeostatic processes that carry over into mature OSNs (energy production, axon maintenance and protein catabolism). The complexity of shifts in gene expression responsible for converting basal cells into neurons was evident in the increased abundance of 203 transcriptional regulators expressed by basal cells and immature OSNs. Conclusions Many of the molecular changes evoked during adult neurogenesis can now be ascribed to specific cellular events in the OSN cell lineage, thereby defining new stages in the development of these neurons. Most notably, the patterns of gene expression in immature OSNs changed in a characteristic fashion as these neurons differentiated. Initial patterns

  2. Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

    SciTech Connect

    Manceur, Aziza P.; Tseng, Michael; Holowacz, Tamara; Witterick, Ian; Weksberg, Rosanna; McCurdy, Richard D.; Warsh, Jerry J.; Audet, Julie

    2011-09-10

    The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.

  3. Olfactory epithelium changes in germfree mice

    PubMed Central

    François, Adrien; Grebert, Denise; Rhimi, Moez; Mariadassou, Mahendra; Naudon, Laurent; Rabot, Sylvie; Meunier, Nicolas

    2016-01-01

    Intestinal epithelium development is dramatically impaired in germfree rodents, but the consequences of the absence of microbiota have been overlooked in other epithelia. In the present study, we present the first description of the bacterial communities associated with the olfactory epithelium and explored differences in olfactory epithelium characteristics between germfree and conventional, specific pathogen-free, mice. While the anatomy of the olfactory epithelium was not significantly different, we observed a thinner olfactory cilia layer along with a decreased cellular turn-over in germfree mice. Using electro-olfactogram, we recorded the responses of olfactory sensitive neuronal populations to various odorant stimulations. We observed a global increase in the amplitude of responses to odorants in germfree mice as well as altered responses kinetics. These changes were associated with a decreased transcription of most olfactory transduction actors and of olfactory xenobiotic metabolising enzymes. Overall, we present here the first evidence that the microbiota modulates the physiology of olfactory epithelium. As olfaction is a major sensory modality for most animal species, the microbiota may have an important impact on animal physiology and behaviour through olfaction alteration. PMID:27089944

  4. Spatial pattern of receptor expression in the olfactory epithelium.

    PubMed Central

    Nef, P; Hermans-Borgmeyer, I; Artières-Pin, H; Beasley, L; Dionne, V E; Heinemann, S F

    1992-01-01

    A PCR-based strategy for amplifying putative receptors involved in murine olfaction was employed to isolate a member (OR3) of the seven-transmembrane-domain receptor superfamily. During development, the first cells that express OR3 appear adjacent to the wall of the telencephalic vesicle at embryonic day 10. The OR3 receptor is uniquely expressed in a subset of olfactory cells that have a characteristic bilateral symmetry in the adult olfactory epithelium. This receptor and its specific pattern of expression may serve a functional role in odor coding or, alternatively, may play a role in the development of the olfactory system. Images PMID:1384038

  5. Olfactory receptor gene expression in tiger salamander olfactory epithelium.

    PubMed

    Marchand, James E; Yang, Xinhai; Chikaraishi, Dona; Krieger, Jurgen; Breer, Heinz; Kauer, John S

    2004-06-28

    Physiological studies of odor-elicited responses from the olfactory epithelium and bulb in the tiger salamander, Ambystoma tigrinum, have elucidated a number of features of olfactory coding that appear to be conserved across several vertebrate species. This animal model has provided an accessible in vivo system for observing individual and ensemble olfactory responses to odorant stimulation using biochemical, neurophysiological, and behavioral assays. In this paper we have complemented these studies by characterizing 35 candidate odorant receptor genes. These receptor sequences are similar to those of the large families of olfactory receptors found in mammals and fish. In situ hybridization, using RNA probes to 20 of these sequences, demonstrates differential distributions of labeled cells across the extent and within the depth of the olfactory epithelium. The distributions of cells labeled with probes to different receptors show spatially restricted patterns that are generally localized to different degrees in medial-lateral and anterior-posterior directions. The patterns of receptor expression in the ventral olfactory epithelium (OE) are mirrored in the dorsal OE. We present a hypothesis as to how the sensory neuron populations expressing different receptor types responding to a particular odorant may relate to the distribution patterns of epithelial and bulbar responses previously characterized using single-unit and voltage-sensitive dye recording methods.

  6. Accessory Olfactory Bulb Function is Modulated by Input from the Main Olfactory Epithelium

    PubMed Central

    Slotnick, Burton; Restrepo, Diego; Schellinck, Heather; Archbold, Georgina; Price, Stephen; Lin, Weihong

    2013-01-01

    While it is now established that sensory neurons in both the main olfactory epithelium and the vomeronasal organ may be activated by both general and pheromonal odorants, it remains unclear what initiates sampling by the VNO. Anterograde transport of wheat germ agglutinin-horseradish peroxidase was used to determine that adequate intranasal syringing with zinc sulfate interrupted all inputs to the main olfactory bulb but left intact those to the accessory olfactory bulb. Adult male treated mice were frankly anosmic when tested with pheromonal and non-pheromonal odors and failed to engage in aggressive behavior. Treated juvenile females failed to show puberty acceleration subsequent to exposure to bedding from adult males. Activation of the immediate early gene c-Fos and electro-vomeronasogram recording confirmed the integrity of the vomeronasal system in zinc sulfate treated mice. These results support the hypothesis that odor detection by the main olfactory epithelium is required to initiate sampling by the vomeronasal system. PMID:20377623

  7. Accessory olfactory bulb function is modulated by input from the main olfactory epithelium.

    PubMed

    Slotnick, Burton; Restrepo, Diego; Schellinck, Heather; Archbold, Georgina; Price, Stephen; Lin, Weihong

    2010-03-01

    Although it is now established that sensory neurons in both the main olfactory epithelium and the vomeronasal organ may be activated by both general and pheromonal odorants, it remains unclear what initiates sampling by the vomeronasal organ. Anterograde transport of wheat germ agglutinin-horseradish peroxidase was used to determine that adequate intranasal syringing with zinc sulfate interrupted all inputs to the main olfactory bulb but left intact those to the accessory olfactory bulb. Adult male treated mice were frankly anosmic when tested with pheromonal and non-pheromonal odors and failed to engage in aggressive behavior. Treated juvenile females failed to show puberty acceleration subsequent to exposure to bedding from adult males. Activation of the immediate early gene c-Fos and electrovomeronasogram recording confirmed the integrity of the vomeronasal system in zinc sulfate-treated mice. These results support the hypothesis that odor detection by the main olfactory epithelium is required to initiate sampling by the vomeronasal system.

  8. Quantum Dot Distribution in the Olfactory Epithelium After Nasal Delivery

    NASA Astrophysics Data System (ADS)

    Garzotto, D.; De Marchis, S.

    2010-10-01

    Nanoparticles are used in a wide range of human applications from industrial to bio-medical fields. However, the unique characteristics of nanoparticles, such as the small size, large surface area per mass and high reactivity raises great concern on the adverse effects of these particles on ecological systems and human health. There are several pioneer studies reporting translocation of inhaled particulates to the brain through a potential neuronal uptake mediated by the olfactory nerve (1, 2, 3). However, no direct evidences have been presented up to now on the pathway followed by the nanoparticles from the nose to the brain. In addition to a neuronal pathway, nanoparticles could gain access to the central nervous system through extracellular pathways (perineuronal, perivascular and cerebrospinal fluid paths). In the present study we investigate the localization of intranasally delivered fluorescent nanoparticles in the olfactory epithelium. To this purpose we used quantum dots (QDs), a model of innovative fluorescent semiconductor nanocrystals commonly used in cell and animal biology (4). Intranasal treatments with QDs were performed acutely on adult CD1 mice. The olfactory epithelium was collected and analysed by confocal microscopy at different survival time after treatment. Data obtained indicate that the neuronal components of the olfactory epithelium are not preferentially involved in QDs uptake, thus suggesting nanoparticles can cross the olfactory epithelium through extracellular pathways.

  9. Odors Discrimination by Olfactory Epithelium Biosensor

    NASA Astrophysics Data System (ADS)

    Liu, Qingjun; Hu, Ning; Ye, Weiwei; Zhang, Fenni; Wang, Hua; Wang, Ping

    2011-09-01

    Humans are exploring the bionic biological olfaction to sense the various trace components of gas or liquid in many fields. For achieving the goal, we endeavor to establish a bioelectronic nose system for odor detection by combining intact bioactive function units with sensors. The bioelectronic nose is based on the olfactory epithelium of rat and microelectrode array (MEA). The olfactory epithelium biosensor generates extracellular potentials in presence of odor, and presents obvious specificity under different odors condition. The odor response signals can be distinguished with each other effectively by signal sorting. On basis of bioactive MEA hybrid system and the improved signal processing analysis, the bioelectronic nose will realize odor discrimination by the specific feature of signals response to various odors.

  10. Scanning electron microscopic studies of the surface morphology of the vomeronasal epithelium and olfactory epithelium of garter snakes.

    PubMed

    Wang, R T; Halpern, M

    1980-04-01

    Fixed vomeronasal and olfactory epithelia from normal adult garter snakes were microdissected, fractured, and examined with a scanning electron microscope. The method permits a detailed comparative study of the structural organization and morphological characteristics of the constituent cells of the vomeronasal and olfactory epithelia. Despite similarities in the nomenclature of the constituent cells in both epithelia, significant differences exist in their surface morphology. A unique columnar structure composed of non-neuronal elements is present in the vomeronasal epithelium. These columns house the bioplar neurons and undifferentiated cells. Such a columnar organization is absent in the olfactory epithelium. In vomeronasal epithelium the bipolar neurons possess microvillous terminals at their dendritic tips, while the dendritic tips of the bipolar neurons of the olfactory epithelium possess cilia. Vomeronasal supporting cells are covered with microvilli, while olfactory supporting cells are covered with cytoplasmic protuberances in addition to the microvilli. In the vomeronasal epithelium the pear-shaped neurons have a grossly smooth surface and are organized into clusters, while in the olfactory epithelium the elliptical bipolar neurons are spinous, aligned side-by-side and interdigitate. The basal (undifferentiated) cell layer in the vomeronasal epithelium has a high packing density and is composed of several layers of irregularly shaped cells. In the olfactory epithelium the basal cell layer is loosely organized and composed of a single layer of oval cells. This information on the three-dimensional cell structure of both epithelia provides a basis for experimental observations on changes in morphology of the bipolar neurons during genesis, development, maturation, degeneration, and regeneration in postnatal, adult animals.

  11. Brain-derived neurotrophic factor (BDNF) expression in normal and regenerating olfactory epithelium of Xenopus laevis.

    PubMed

    Frontera, Jimena Laura; Cervino, Ailen Soledad; Jungblut, Lucas David; Paz, Dante Agustín

    2015-03-01

    Olfactory epithelium has the capability to continuously regenerate olfactory receptor neurons throughout life. Adult neurogenesis results from proliferation and differentiation of neural stem cells, and consequently, olfactory neuroepithelium offers an excellent opportunity to study neural regeneration and the factors involved in the maintenance and regeneration of all their cell types. We analyzed the expression of BDNF in the olfactory system under normal physiological conditions as well as during a massive regeneration induced by chemical destruction of the olfactory epithelium in Xenopus laevis larvae. We described the expression and presence of BDNF in the olfactory epithelium and bulb. In normal physiological conditions, sustentacular (glial) cells and a few scattered basal (stem) cells express BDNF in the olfactory epithelium as well as the granular cells in the olfactory bulb. Moreover, during massive regeneration, we demonstrated a drastic increase in basal cells expressing BDNF as well as an increase in BDNF in the olfactory bulb and nerve. Together these results suggest an important role of BDNF in the maintenance and regeneration of the olfactory system.

  12. Are pheromones detected through the main olfactory epithelium?

    PubMed

    Wang, Zhenshan; Nudelman, Aaron; Storm, Daniel R

    2007-06-01

    A major sensory organ for the detection of pheromones by animals is the vomeronasal organ (VNO). Although pheromones control the behaviors of various species, the effect of pheromones on human behavior has been controversial because the VNO is not functional in adults. However, recent genetic, biochemical, and electrophysiological data suggest that some pheromone-based behaviors, including male sexual behavior in mice, are mediated through the main olfactory epithelium (MOE) and are coupled to the type 3 adenylyl cyclase (AC3) and a cyclic nucleotide-gated (CNG) ion channel. These recent discoveries suggest the provocative hypothesis that human pheromones may signal through the MOE.

  13. Cell cycle of globose basal cells in rat olfactory epithelium.

    PubMed

    Huard, J M; Schwob, J E

    1995-05-01

    The olfactory epithelium of adult mammals has the unique property of generating olfactory sensory neurons throughout life. Cells of the basal compartment, which include horizontal and globose basal cells, are responsible for the ongoing process of neurogenesis in this system. We report here that the globose basal cells in olfactory epithelium of rats, as in mice, are the predominant type of proliferating cell, and account for 97.6% of the actively dividing cells in the basal compartment of the normal epithelium. Globose basal cells have not been fully characterized in terms of their proliferative properties, and the dynamic aspects of neurogenesis are not well understood. As a consequence, it is uncertain whether cell kinetic properties are under any regulation that could affect the rate of neurogenesis. To address this gap in our knowledge, we have determined the duration of both the synthesis phase (S-phase) and the full cell cycle of globose basal cells in adult rats. The duration of the S-phase was found to be 9 hr in experiments utilizing sequential injections of either IdU followed by BrdU or 3H-thy followed by BrdU. The duration of the cell cycle was determined by varying the time interval between the injections of 3H-thy and BrdU and tracking the set of cells that exit S shortly after the first injection. With this paradigm, the interval required for these cells to traverse G2, M, G1, and a second S-phase, is equivalent to the duration of one mitotic cycle and equals 17 hr. These observations serve as the foundation to assess whether the cell cycle duration is subject to regulation in response to experimental injury, and whether such regulation is partly responsible for changes in the rate of neurogenesis in such settings.

  14. Olfactory epithelium in the olfactory recess: a case study in new world leaf-nosed bats.

    PubMed

    Eiting, Thomas P; Smith, Timothy D; Dumont, Elizabeth R

    2014-11-01

    The olfactory recess (OR) is a restricted space at the back of the nasal fossa in many mammals that is thought to improve olfactory function. Mammals that have an olfactory recess are usually described as keen-scented, while those that do not are typically thought of as less reliant on olfaction. However, the presence of an olfactory recess is not a binary trait. Many mammal families have members that vary substantially in the size and complexity of the olfactory recess. There is also variation in the amount of olfactory epithelium (OE) that is housed in the olfactory recess. Among New World leaf-nosed bats (family Phyllostomidae), species vary by over an order of magnitude in how much of their total OE lies within the OR. Does this variation relate to previously documented neuroanatomical proxies for olfactory reliance? Using data from 12 species of phyllostomid bats, we addressed the hypothesis that the amount of OE within the OR relates to a species' dependence on olfaction, as measured by two commonly used neuroanatomical metrics, the size of the olfactory bulb, and the number of glomeruli in the olfactory bulb, which are the first processing units within the olfactory signal cascade. We found that the percentage of OE within the OR does not relate to either measure of olfactory "ability." This suggests that olfactory reliance is not reflected in the size of the olfactory recess. We explore other roles that the olfactory recess may play.

  15. The location of olfactory receptors within olfactory epithelium is independent of odorant volatility and solubility

    PubMed Central

    2011-01-01

    Background Our objective was to study the pattern of olfactory receptor expression within the dorsal and ventral regions of the mouse olfactory epithelium. We hypothesized that olfactory receptors were distributed based on the chemical properties of their ligands: e.g. receptors for polar, hydrophilic and weakly volatile odorants would be present in the dorsal region of olfactory epithelium; while receptors for non-polar, more volatile odorants would be distributed to the ventral region. To test our hypothesis, we used micro-transplantation of cilia-enriched plasma membranes derived from dorsal or ventral regions of the olfactory epithelium into Xenopus oocytes for electrophysiological characterization against a panel of 100 odorants. Findings Odorants detected by ORs from the dorsal and ventral regions showed overlap in volatility and water solubility. We did not find evidence for a correlation between the solubility and volatility of odorants and the functional expression of olfactory receptors in the dorsal or ventral region of the olfactory epithelia. Conclusions No simple clustering or relationship between chemical properties of odorants could be associated with the different regions of the olfactory epithelium. These results suggest that the location of ORs within the epithelium is not organized based on the physico-chemical properties of their ligands. PMID:21548958

  16. Compensatory plasticity in the olfactory epithelium: age, timing, and reversibility

    PubMed Central

    Barber, Casey N.

    2015-01-01

    Like other biological systems, olfaction responds “homeostatically” to enduring change in the stimulus environment. This adaptive mechanism, referred to as compensatory plasticity, has been studied almost exclusively in developing animals. Thus it is unknown if this phenomenon is limited to ontogenesis and irreversible, characteristics common to some other forms of plasticity. Here we explore the effects of odor deprivation on the adult mouse olfactory epithelium (OE) using nasal plugs to eliminate nasal airflow unilaterally. Plugs were in place for 2–6 wk after which electroolfactograms (EOGs) were recorded from the occluded and open sides of the nasal cavity. Mean EOG amplitudes were significantly greater on the occluded than on the open side. The duration of plugging did not affect the results, suggesting that maximal compensation occurs within 2 wk or less. The magnitude of the EOG difference between the open and occluded side in plugged mice was comparable to adults that had undergone surgical naris occlusion as neonates. When plugs were removed after 4 wk followed by 2 wk of recovery, mean EOG amplitudes were not significantly different between the always-open and previously plugged sides of the nasal cavity suggesting that this form of plasticity is reversible. Taken together, these results suggest that compensatory plasticity is a constitutive mechanism of olfactory receptor neurons that allows these cells to recalibrate their stimulus-response relationship to fit the statistics of their current odor environment. PMID:26269548

  17. Responses of the Rat Olfactory Epithelium to Retronasal Air Flow

    PubMed Central

    Scott, John W.; Acevedo, Humberto P.; Sherrill, Lisa; Phan, Maggie

    2008-01-01

    Responses of the rat olfactory epithelium were assessed with the electroolfactogram while odorants were presented to the external nares with an artificial sniff or to the internal nares by positive pressure. A series of seven odorants that varied from very polar, hydrophilic odorants to very non-polar, hydrophobic odorants were used. While the polar odorants activated the dorsal olfactory epithelium when presented by the external nares (orthonasal presentation), they were not effective when forced through the nasal cavity from the internal nares (retronasal presentation). However, the non-polar odorants were effective in both stimulus modes. These results were independent of stimulus concentration or of humidity of the carrier air. Similar results were obtained with multiunit recording from olfactory bulb. These results help to explain why human investigations often report differences in the sensation or ability to discriminate odorants presented orthonasally vs. retronasally. The results also strongly support the importance of odorant sorption in normal olfactory processes. PMID:17215498

  18. Intranasal Location and Immunohistochemical Characterization of the Equine Olfactory Epithelium

    PubMed Central

    Kupke, Alexandra; Wenisch, Sabine; Failing, Klaus; Herden, Christiane

    2016-01-01

    The olfactory epithelium (OE) is the only body site where neurons contact directly the environment and are therefore exposed to a broad variation of substances and insults. It can serve as portal of entry for neurotropic viruses which spread via the olfactory pathway to the central nervous system. For horses, it has been proposed and concluded mainly from rodent studies that different viruses, e.g., Borna disease virus, equine herpesvirus 1 (EHV-1), hendra virus, influenza virus, rabies virus, vesicular stomatitis virus can use this route. However, little is yet known about cytoarchitecture, protein expression and the intranasal location of the equine OE. Revealing differences in cytoarchitecture or protein expression pattern in comparison to rodents, canines, or humans might help to explain varying susceptibility to certain intranasal virus infections. On the other hand, disclosing similarities especially between rodents and other species, e.g., horses would help to underscore transferability of rodent models. Analysis of the complete noses of five adult horses revealed that in the equine OE two epithelial subtypes with distinct marker expression exist, designated as types a and b which resemble those previously described in dogs. Detailed statistical analysis was carried out to confirm the results obtained on the descriptive level. The equine OE was predominantly located in caudodorsal areas of the nasal turbinates with a significant decline in rostroventral direction, especially for type a. Immunohistochemically, olfactory marker protein and doublecortin (DCX) expression was found in more cells of OE type a, whereas expression of proliferating cell nuclear antigen and tropomyosin receptor kinase A was present in more cells of type b. Accordingly, type a resembles the mature epithelium, in contrast to the more juvenile type b. Protein expression profile was comparable to canine and rodent OE but equine types a and b were located differently within the nose and

  19. The Olfactory Neural Epithelium As a Tool in Neuroscience.

    PubMed

    Lavoie, Joëlle; Gassó Astorga, Patricia; Segal-Gavish, Hadar; Wu, YeeWen Candace; Chung, Youjin; Cascella, Nicola G; Sawa, Akira; Ishizuka, Koko

    2017-02-01

    Capturing both dynamic changes (state) and persistent signatures (trait) directly associated with disease at the molecular level is crucial in modern medicine. The olfactory neural epithelium, easily accessible in clinical settings, is a promising surrogate model in translational brain medicine, complementing the limitations in current engineered cell models.

  20. Endocannabinoid modulation in the olfactory epithelium.

    PubMed

    Breunig, Esther; Czesnik, Dirk; Piscitelli, Fabiana; Di Marzo, Vincenzo; Manzini, Ivan; Schild, Detlev

    2010-01-01

    Appetite, food intake, and energy balance are closely linked to the endocannabinoid system in the central nervous system. Now, endocannabinoid modulation has been discovered in the peripheral olfactory system of larval Xenopus laevis. The endocannabinoid 2-AG has been shown to influence odorant-detection thresholds according to the hunger state of the animal. Hungry animals have increased 2-AG levels due to enhanced synthesis of 2-AG in sustentacular supporting cells. This renders olfactory receptor neurons, exhibiting CB1 receptors, more sensitive at detecting lower odorant concentrations, which probably helps the animal to locate food. Since taste and vision are also influenced by endocannabinoids, this kind of modulation might boost sensory inputs of food in hungry animals.

  1. Expression and differential localization of xenobiotic transporters in the rat olfactory neuro-epithelium.

    PubMed

    Thiebaud, Nicolas; Menetrier, Franck; Belloir, Christine; Minn, Anne-Laure; Neiers, Fabrice; Artur, Yves; Le Bon, Anne-Marie; Heydel, Jean-Marie

    2011-11-14

    Transporters, such as multidrug resistance P-glycoproteins (MDR), multidrug resistance-related proteins (MRP) and organic anion transporters (OATs), are involved in xenobiotic metabolism, particularly the cellular uptake or efflux of xenobiotics (and endobiotics) or their metabolites. The olfactory epithelium is exposed to both inhaled xenobiotics and those coming from systemic circulation. This tissue has been described as a pathway for xenobiotics to the brain via olfactory perineural space. Thereby, olfactory transporters and xenobiotic metabolizing enzymes, dedicated to the inactivation and the elimination of xenobiotics, have been involved in the toxicological protection of the brain, the olfactory epithelium itself and the whole body. These proteins could also have a role in the preservation of the olfactory sensitivity by inactivation and clearance of the excess of odorant molecules from the perireceptor space. The goal of the present study was to increase our understanding of the expression and the localization of transporters in this tissue. For most of the studied transporters, we observed an opposite mRNA expression pattern (RT-PCR) in the olfactory epithelium compared to the liver, which is considered to be the main metabolic organ. Olfactory epithelium mainly expressed efflux transporters (MRP, MDR). However, a similar pattern was observed between the olfactory epithelium and the olfactory bulb. We also demonstrate distinct cellular immunolocalization of the transporters in the olfactory epithelium. As previously reported, Mrp1 was mainly found in the supranuclear portions of supporting cells. In addition, Mrp3 and Mrp5 proteins, which were detected for the first time in olfactory epithelium, were localized to the olfactory neuron layer, while Mdr1 was localized to the capillary endothelium of lymphatic vessels in the subepithelial region. The pattern of expression and the distinct localization of the olfactory transporters showed in this work may

  2. Inducible activation of ERK5 MAP kinase enhances adult neurogenesis in the olfactory bulb and improves olfactory function.

    PubMed

    Wang, Wenbin; Lu, Song; Li, Tan; Pan, Yung-Wei; Zou, Junhui; Abel, Glen M; Xu, Lihong; Storm, Daniel R; Xia, Zhengui

    2015-05-20

    Recent discoveries have suggested that adult neurogenesis in the subventricular zone (SVZ) and olfactory bulb (OB) may be required for at least some forms of olfactory behavior in mice. However, it is unclear whether conditional and selective enhancement of adult neurogenesis by genetic approaches is sufficient to improve olfactory function under physiological conditions or after injury. Furthermore, specific signaling mechanisms regulating adult neurogenesis in the SVZ/OB are not fully defined. We previously reported that ERK5, a MAP kinase selectively expressed in the neurogenic regions of the adult brain, plays a critical role in adult neurogenesis in the SVZ/OB. Using a site-specific knock-in mouse model, we report here that inducible and targeted activation of the endogenous ERK5 in adult neural stem/progenitor cells enhances adult neurogenesis in the OB by increasing cell survival and neuronal differentiation. This conditional ERK5 activation also improves short-term olfactory memory and odor-cued associative olfactory learning under normal physiological conditions. Furthermore, these mice show enhanced recovery of olfactory function and have more adult-born neurons after a zinc sulfate-induced lesion of the main olfactory epithelium. We conclude that ERK5 MAP kinase is an important endogenous signaling pathway regulating adult neurogenesis in the SVZ/OB, and that conditional activation of endogenous ERK5 is sufficient to enhance adult neurogenesis in the OB thereby improving olfactory function both under normal conditions and after injury.

  3. Global Expression Profiling of Globose Basal Cells and Neurogenic Progression Within the Olfactory Epithelium

    PubMed Central

    Krolewski, Richard C.; Packard, Adam; Schwob, James E.

    2013-01-01

    Ongoing, lifelong neurogenesis maintains the neuronal population of the olfactory epithelium in the face of piecemeal neuronal turnover and restores it following wholesale loss. The molecular phenotypes corresponding to different stages along the progression from multipotent globose basal cell (GBC) progenitor to differentiated olfactory sensory neuron are poorly characterized. We used the transgenic expression of enhanced green fluorescent protein (eGFP) and cell surface markers to FACS-isolate ΔSox2-eGFP(+) GBCs, Neurog1-eGFP(+) GBCs and immature neurons, and ΔOMP-eGFP(+) mature neurons from normal adult mice. In addition, the latter two populations were also collected 3 weeks after olfactory bulb ablation, a lesion that results in persistently elevated neurogenesis. Global profiling of mRNA from the populations indicates that all stages of neurogenesis share a cohort of >2,100 genes that are upregulated compared to sustentacular cells. A further cohort of >1,200 genes are specifically upregulated in GBCs as compared to sustentacular cells and differentiated neurons. The increased rate of neurogenesis caused by olfactory bulbectomy had little effect on the transcriptional profile of the Neurog1-eGFP(+) population. In contrast, the abbreviated lifespan of ΔOMP-eGFP(+) neurons born in the absence of the bulb correlated with substantial differences in gene expression as compared to the mature neurons of the normal epithelium. Detailed examination of the specific genes upregulated in the different progenitor populations revealed that the chromatin modifying complex proteins LSD1 and coREST were expressed sequentially in upstream ΔSox2-eGFP(+) GBCs and Neurog1-eGFP(+) GBCs/immature neurons. The expression patterns of these proteins are dynamically regulated after activation of the epithelium by methyl bromide lesion. PMID:22847514

  4. Tonic and Phasic Receptor Neurons in the Vertebrate Olfactory Epithelium

    PubMed Central

    Madrid, Rodolfo; Sanhueza, Magdalena; Alvarez, Osvaldo; Bacigalupo, Juan

    2003-01-01

    Olfactory receptor neurons (ORNs) respond to odorants with characteristic patterns of action potentials that are relevant for odor coding. Prolonged odorant exposures revealed three populations of dissociated toad ORNs, which were mimicked by depolarizing currents: tonic (TN, displaying sustained firing, 49% of 102 cells), phasic (PN, exhibiting brief action potential trains, 36%) and intermediate neurons (IN, generating trains longer than PN, 15%). We studied the biophysical properties underlying the differences between TNs and PNs, the most extreme cases among ORNs. TNs and PNs possessed similar membrane capacitances (∼4 pF), but they differed in resting potential (−82 versus −64 mV), input resistance (4.2 versus 2.9 GΩ) and unspecific current, Iu (TNs: 0 < Iu ≤ 1 pA/pF; and PNs: Iu > 1 pA/pF). Firing behavior did not correlate with differences in voltage-gated conductances. We developed a mathematical model that accurately simulates tonic and phasic patterns. Whole cell recordings from rat ORNs in fragments (∼4 mm2) of olfactory epithelium showed that such a tissue normally contains tonic and phasic receptor neurons, suggesting that this feature is common across a wide range of vertebrates. Our findings show that the individual passive electrical properties can govern the firing patterns of ORNs. PMID:12770919

  5. BDNF promoter-mediated beta-galactosidase expression in the olfactory epithelium and bulb.

    PubMed

    Clevenger, Amy C; Salcedo, Ernesto; Jones, Kevin R; Restrepo, Diego

    2008-07-01

    The neurotrophin brain-derived neurotrophic factor (BDNF) has been implicated in the generation and differentiation of new olfactory sensory neurons (OSNs) and in the regulation of branching of OSN axons in their target glomeruli. However, previous reports of BDNF mRNA and protein expression in olfactory epithelium and olfactory bulb (OB) have been inconsistent, raising questions on the proposed roles for BDNF. Here, we report on beta-galactosidase (beta-gal) expression in adult gene-targeted mice where the BDNF promoter drives expression of the Escherichia coli lacZ gene (BDNF(lacZneo) mice). We find that beta-gal is expressed in a small subset of OSNs with axons that reach the olfactory nerve layers throughout the OB. In the OB, we find expression of beta-gal in gamma-aminobutyric acidergic but not dopaminergic periglomerular cells and external tufted cells and in interneurons located in the mitral cell layer. Our results are inconsistent with the regulation of generation and differentiation of new OSNs elicited by the release of BDNF from horizontal basal cells. The results are consistent with a role for BDNF in competitive branching of OSN axons within the glomeruli of the OB.

  6. High Fructose Diet inducing diabetes rapidly impacts olfactory epithelium and behavior in mice

    PubMed Central

    Rivière, Sébastien; Soubeyre, Vanessa; Jarriault, David; Molinas, Adrien; Léger-Charnay, Elise; Desmoulins, Lucie; Grebert, Denise; Meunier, Nicolas; Grosmaitre, Xavier

    2016-01-01

    Type 2 Diabetes (T2D), a major public health issue reaching worldwide epidemic, has been correlated with lower olfactory abilities in humans. As olfaction represents a major component of feeding behavior, its alteration may have drastic consequences on feeding behaviors that may in turn aggravates T2D. In order to decipher the impact of T2D on the olfactory epithelium, we fed mice with a high fructose diet (HFruD) inducing early diabetic state in 4 to 8 weeks. After only 4 weeks of this diet, mice exhibited a dramatic decrease in olfactory behavioral capacities. Consistently, this decline in olfactory behavior was correlated to decreased electrophysiological responses of olfactory neurons recorded as a population and individually. Our results demonstrate that, in rodents, olfaction is modified by HFruD-induced diabetes. Functional, anatomical and behavioral changes occurred in the olfactory system at a very early stage of the disease. PMID:27659313

  7. An endocannabinoid system is present in the mouse olfactory epithelium but does not modulate olfaction

    PubMed Central

    Hutch, Chelsea; Hillard, Cecilia J.; Jia, Cuihong; Hegg, Colleen C.

    2015-01-01

    Endocannabinoids modulate a diverse array of functions including progenitor cell proliferation in the central nervous system, and odorant detection and food intake in the mammalian central olfactory system and larval Xenopus laevis peripheral olfactory system. However, the presence and role of endocannabinoids in the peripheral olfactory epithelium has not been examined in mammals. We found the presence of cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2) receptor protein and mRNA in the olfactory epithelium. Using either immunohistochemistry or calcium imaging we localized CB1 receptors on neurons, glia like sustentacular cells, microvillous cells and progenitor-like basal cells. To examine the role of endocannabinoids, CB1 and CB2 receptor deficient (CB1−/−/CB2−/−) mice were used. The endocannabinoid 2-arachidonylglycerol (2-AG) was present at high levels in both C57BL/6 wildtype and CB1−/−/CB2−/− mice. 2-AG synthetic and degradative enzymes are expressed in wildtype mice. A small but significant decrease in basal cell and olfactory sensory neuron numbers was observed in CB1−/−/CB2−/− mice compared to wildtype mice. The decrease in olfactory sensory neurons did not translate to impairment in olfactory-mediated behaviors assessed by the buried food test and habituation/dishabituation test. Collectively, these data indicate the presence of an endocannabinoid system in the mouse olfactory epithelium. However, unlike in tadpoles, endocannabinoids do not modulate olfaction. Further investigation on the role of endocannabinoids in progenitor cell function in the olfactory epithelium is warranted. PMID:26037800

  8. Lesion of the olfactory epithelium accelerates prion neuroinvasion and disease onset when prion replication is restricted to neurons.

    PubMed

    Crowell, Jenna; Wiley, James A; Bessen, Richard A

    2015-01-01

    Natural prion diseases of ruminants are moderately contagious and while the gastrointestinal tract is the primary site of prion agent entry, other mucosae may be entry sites in a subset of infections. In the current study we examined prion neuroinvasion and disease induction following disruption of the olfactory epithelium in the nasal mucosa since this site contains environmentally exposed olfactory sensory neurons that project directly into the central nervous system. Here we provide evidence for accelerated prion neuroinvasion and clinical onset from the olfactory mucosa after disruption and regeneration of the olfactory epithelium and when prion replication is restricted to neurons. In transgenic mice with neuron restricted replication of prions, there was a reduction in survival when the olfactory epithelium was disrupted prior to intranasal inoculation and there was >25% decrease in the prion incubation period. In a second model, the neurotropic DY strain of transmissible mink encephalopathy was not pathogenic in hamsters by the nasal route, but 50% of animals exhibited brain infection and/or disease when the olfactory epithelium was disrupted prior to intranasal inoculation. A time course analysis of prion deposition in the brain following loss of the olfactory epithelium in models of neuron-restricted prion replication suggests that neuroinvasion from the olfactory mucosa is via the olfactory nerve or brain stem associated cranial nerves. We propose that induction of neurogenesis after damage to the olfactory epithelium can lead to prion infection of immature olfactory sensory neurons and accelerate prion spread to the brain.

  9. Lesion of the Olfactory Epithelium Accelerates Prion Neuroinvasion and Disease Onset when Prion Replication Is Restricted to Neurons

    PubMed Central

    Crowell, Jenna; Wiley, James A.; Bessen, Richard A.

    2015-01-01

    Natural prion diseases of ruminants are moderately contagious and while the gastrointestinal tract is the primary site of prion agent entry, other mucosae may be entry sites in a subset of infections. In the current study we examined prion neuroinvasion and disease induction following disruption of the olfactory epithelium in the nasal mucosa since this site contains environmentally exposed olfactory sensory neurons that project directly into the central nervous system. Here we provide evidence for accelerated prion neuroinvasion and clinical onset from the olfactory mucosa after disruption and regeneration of the olfactory epithelium and when prion replication is restricted to neurons. In transgenic mice with neuron restricted replication of prions, there was a reduction in survival when the olfactory epithelium was disrupted prior to intranasal inoculation and there was >25% decrease in the prion incubation period. In a second model, the neurotropic DY strain of transmissible mink encephalopathy was not pathogenic in hamsters by the nasal route, but 50% of animals exhibited brain infection and/or disease when the olfactory epithelium was disrupted prior to intranasal inoculation. A time course analysis of prion deposition in the brain following loss of the olfactory epithelium in models of neuron-restricted prion replication suggests that neuroinvasion from the olfactory mucosa is via the olfactory nerve or brain stem associated cranial nerves. We propose that induction of neurogenesis after damage to the olfactory epithelium can lead to prion infection of immature olfactory sensory neurons and accelerate prion spread to the brain. PMID:25822718

  10. Progressive effects of N-myc deficiency on proliferation, neurogenesis, and morphogenesis in the olfactory epithelium.

    PubMed

    Wittmann, Walter; Schimmang, Thomas; Gunhaga, Lena

    2014-06-01

    N-myc belongs to the myc proto-oncogene family, which is involved in numerous cellular processes such as proliferation, growth, apoptosis, and differentiation. Conditional deletion of N-myc in the mouse nervous system disrupted brain development, indicating that N-myc plays an essential role during neural development. How the development of the olfactory epithelium and neurogenesis within are affected by the loss of N-myc has, however, not been determined. To address these issues, we examined an N-myc(Foxg1Cre) conditional mouse line, in which N-myc is depleted in the olfactory epithelium. First changes in N-myc mutants were detected at E11.5, with reduced proliferation and neurogenesis in a slightly smaller olfactory epithelium. The phenotype was more pronounced at E13.5, with a complete lack of Hes5-positive progenitor cells, decreased proliferation, and neurogenesis. In addition, stereological analyses revealed reduced cell size of post-mitotic neurons in the olfactory epithelium, which contributed to a smaller olfactory pit. Furthermore, we observed diminished proliferation and neurogenesis also in the vomeronasal organ, which likewise was reduced in size. In addition, the generation of gonadotropin-releasing hormone neurons was severely reduced in N-myc mutants. Thus, diminished neurogenesis and proliferation in combination with smaller neurons might explain the morphological defects in the N-myc depleted olfactory structures. Moreover, our results suggest an important role for N-myc in regulating ongoing neurogenesis, in part by maintaining the Hes5-positive progenitor pool. In summary, our results provide evidence that N-myc deficiency in the olfactory epithelium progressively diminishes proliferation and neurogenesis with negative consequences at structural and cellular levels.

  11. Olfactory epithelium biosensor: odor discrimination of receptor neurons from a bio-hybrid sensing system.

    PubMed

    Liu, Qingjun; Hu, Ning; Zhang, Fenni; Zhang, Diming; Hsia, K Jimmy; Wang, Ping

    2012-12-01

    Bio-hybrid systems provide an opportunity for integrating a living bio-active unit and a proper biosensing system, to employ the unique properties of the bio-active unit. The biological olfactory system can sense and identify thousands of trace odors. The purpose of this study is to combine olfactory epithelium with microelectrode array (MEA) to establish an olfactory epithelium-MEA hybrid system to record the odor-induced electrophysiological activities of the tissue. In our experiments, extracellular potential of olfactory receptor neurons in intact epithelium were measured in the presence of ethyl ether, acetic acid, butanedione, and acetone, respectively. After the odor-induced response signals were analyzed in the time and frequency domain, the temporal characteristics of response signals were extracted. We found that olfactory epithelium-MEA hybrid system can reflect the in vitro odor information of different signal characteristics and firing modes in vitro. The bio-hybrid sensing system can represent a useful instrument to sense and detect the odorant molecules with well recognizing patterns. With the development of sensor technology, bio-hybrid systems will represent emerging and promising platforms for wide applications, ranging from health care to environmental monitoring.

  12. Ultrastructure of the olfactory epithelium in a flatfish, barfin flounder (Verasper moseri).

    PubMed

    Nakamuta, Shoko; Nakamuta, Nobuaki; Taniguchi, Kazuyuki

    2010-06-01

    In this study, we examined the olfactory epithelium (OE) of the barfin flounder by transmission electron microscopy. As in the case of the ordinary teleost, the OE of the barfin flounder had 3 types of olfactory receptor cells (ciliated olfactory receptor cell, microvillous olfactory receptor cell and crypt cell), 3 types of supporting cells (ciliated, microvillous and crypt supporting cells) and basal cells. Each type of OE cells in the barfin flounder had similar ultrastructure to that of the ordinary teleost. Crypt cell is the third type of olfactory receptor cell unique to fish, whose function is unclear. The barfin flounder may be a suitable material to study crypt cells because it has relatively abundant crypt cells in the OE.

  13. Molecular signatures associated with cognitive deficits in schizophrenia: a study of biopsied olfactory neural epithelium

    PubMed Central

    Horiuchi, Y; Kondo, M A; Okada, K; Takayanagi, Y; Tanaka, T; Ho, T; Varvaris, M; Tajinda, K; Hiyama, H; Ni, K; Colantuoni, C; Schretlen, D; Cascella, N G; Pevsner, J; Ishizuka, K; Sawa, A

    2016-01-01

    Cognitive impairment is a key feature of schizophrenia (SZ) and determines functional outcome. Nonetheless, molecular signatures in neuronal tissues that associate with deficits are not well understood. We conducted nasal biopsy to obtain olfactory epithelium from patients with SZ and control subjects. The neural layers from the biopsied epithelium were enriched by laser-captured microdissection. We then performed an unbiased microarray expression study and implemented a systematic neuropsychological assessment on the same participants. The differentially regulated genes in SZ were further filtered based on correlation with neuropsychological traits. This strategy identified the SMAD 5 gene, and real-time quantitative PCR analysis also supports downregulation of the SMAD pathway in SZ. The SMAD pathway has been important in multiple tissues, including the role for neurodevelopment and bone formation. Here the involvement of the pathway in adult brain function is suggested. This exploratory study establishes a strategy to better identify neuronal molecular signatures that are potentially associated with mental illness and cognitive deficits. We propose that the SMAD pathway may be a novel target in addressing cognitive deficit of SZ in future studies. PMID:27727244

  14. Early survival factor deprivation in the olfactory epithelium enhances activity-driven survival

    PubMed Central

    François, Adrien; Laziz, Iman; Rimbaud, Stéphanie; Grebert, Denise; Durieux, Didier; Pajot-Augy, Edith; Meunier, Nicolas

    2013-01-01

    The neuronal olfactory epithelium undergoes permanent renewal because of environmental aggression. This renewal is partly regulated by factors modulating the level of neuronal apoptosis. Among them, we had previously characterized endothelin as neuroprotective. In this study, we explored the effect of cell survival factor deprivation in the olfactory epithelium by intranasal delivery of endothelin receptors antagonists to rat pups. This treatment induced an overall increase of apoptosis in the olfactory epithelium. The responses to odorants recorded by electroolfactogram were decreased in treated animal, a result consistent with a loss of olfactory sensory neurons (OSNs). However, the treated animal performed better in an olfactory orientation test based on maternal odor compared to non-treated littermates. This improved performance could be due to activity-dependent neuronal survival of OSNs in the context of increased apoptosis level. In order to demonstrate it, we odorized pups with octanal, a known ligand for the rI7 olfactory receptor (Olr226). We quantified the number of OSN expressing rI7 by RT-qPCR and whole mount in situ hybridization. While this number was reduced by the survival factor removal treatment, this reduction was abolished by the presence of its ligand. This improved survival was optimal for low concentration of odorant and was specific for rI7-expressing OSNs. Meanwhile, the number of rI7-expressing OSNs was not affected by the odorization in non-treated littermates; showing that the activity-dependant survival of OSNs did not affect the OSN population during the 10 days of odorization in control conditions. Overall, our study shows that when apoptosis is promoted in the olfactory mucosa, the activity-dependent neuronal plasticity allows faster tuning of the olfactory sensory neuron population toward detection of environmental odorants. PMID:24399931

  15. Early survival factor deprivation in the olfactory epithelium enhances activity-driven survival.

    PubMed

    François, Adrien; Laziz, Iman; Rimbaud, Stéphanie; Grebert, Denise; Durieux, Didier; Pajot-Augy, Edith; Meunier, Nicolas

    2013-01-01

    The neuronal olfactory epithelium undergoes permanent renewal because of environmental aggression. This renewal is partly regulated by factors modulating the level of neuronal apoptosis. Among them, we had previously characterized endothelin as neuroprotective. In this study, we explored the effect of cell survival factor deprivation in the olfactory epithelium by intranasal delivery of endothelin receptors antagonists to rat pups. This treatment induced an overall increase of apoptosis in the olfactory epithelium. The responses to odorants recorded by electroolfactogram were decreased in treated animal, a result consistent with a loss of olfactory sensory neurons (OSNs). However, the treated animal performed better in an olfactory orientation test based on maternal odor compared to non-treated littermates. This improved performance could be due to activity-dependent neuronal survival of OSNs in the context of increased apoptosis level. In order to demonstrate it, we odorized pups with octanal, a known ligand for the rI7 olfactory receptor (Olr226). We quantified the number of OSN expressing rI7 by RT-qPCR and whole mount in situ hybridization. While this number was reduced by the survival factor removal treatment, this reduction was abolished by the presence of its ligand. This improved survival was optimal for low concentration of odorant and was specific for rI7-expressing OSNs. Meanwhile, the number of rI7-expressing OSNs was not affected by the odorization in non-treated littermates; showing that the activity-dependant survival of OSNs did not affect the OSN population during the 10 days of odorization in control conditions. Overall, our study shows that when apoptosis is promoted in the olfactory mucosa, the activity-dependent neuronal plasticity allows faster tuning of the olfactory sensory neuron population toward detection of environmental odorants.

  16. Neural regeneration dynamics of Xenopus laevis olfactory epithelium after zinc sulfate-induced damage.

    PubMed

    Frontera, J L; Raices, M; Cervino, A S; Pozzi, A G; Paz, D A

    2016-11-01

    Neural stem cells (NSCs) of the olfactory epithelium (OE) are responsible for tissue maintenance and the neural regeneration after severe damage of the tissue. In the normal OE, NSCs are located in the basal layer, olfactory receptor neurons (ORNs) mainly in the middle layer, and sustentacular (SUS) cells in the most apical olfactory layer. In this work, we induced severe damage of the OE through treatment with a zinc sulfate (ZnSO4) solution directly in the medium, which resulted in the loss of ORNs and SUS cells, but retention of the basal layer. During recovery following injury, the OE exhibited increased proliferation of NSCs and rapid neural regeneration. After 24h of recovery, new ORNs and SUS cells were observed. Normal morphology and olfactory function were reached after 168h (7 days) of recovery after ZnSO4 treatment. Taken together, these data support the hypothesis that NSCs in the basal layer activate after OE injury and that these are sufficient for complete neural regeneration and olfactory function restoration. Our analysis provides histological and functional insights into the dynamics between olfactory neurogenesis and the neuronal integration into the neuronal circuitry of the olfactory bulb that restores the function of the olfactory system.

  17. CD36 is expressed in a defined subpopulation of neurons in the olfactory epithelium

    PubMed Central

    Xavier, André Machado; Ludwig, Raissa Guimarães; Nagai, Maíra Harume; de Almeida, Tiago Jonas; Watanabe, Hebe Mizuno; Hirata, Marcio Yukio; Rosenstock, Tatiana Rosado; Papes, Fabio; Malnic, Bettina; Glezer, Isaias

    2016-01-01

    The sensory neurons in the olfactory epithelium (OSNs) are equipped with a large repertoire of olfactory receptors and the associated signal transduction machinery. In addition to the canonical OSNs, which express odorant receptors (ORs), the epithelium contains specialized subpopulations of sensory neurons that can detect specific information from environmental cues and relay it to relevant neuronal circuitries. Here we describe a subpopulation of mature OSNs in the main olfactory epithelium (MOE) which expresses CD36, a multifunctional receptor involved in a series of biological processes, including sensory perception of lipid ligands. The Cd36 expressing neurons coexpress markers of mature OSNs and are dispersed throughout the MOE. Unlike several ORs analyzed in our study, we found frequent coexpression of the OR Olfr287 in these neurons, suggesting that only a specific set of ORs may be coexpressed with CD36 in OSNs. We also show that CD36 is expressed in the cilia of OSNs, indicating a possible role in odorant detection. CD36-deficient mice display no signs of gross changes in the organization of the olfactory epithelium, but show impaired preference for a lipid mixture odor. Our results show that CD36-expressing neurons represent a distinct population of OSNs, which may have specific functions in olfaction. PMID:27145700

  18. Microvillous cells expressing IP3R3 in the olfactory epithelium of mice

    PubMed Central

    Hegg, Colleen C.; Jia, Cuihong; Chick, Wallace S.; Restrepo, Diego; Hansen, Anne

    2015-01-01

    Microvillous cells of the main olfactory epithelium have been described variously as primary olfactory neurons, secondary chemosensory cells, or non-sensory cells. Here we generated an IP3R3tm1(tauGFP) mouse in which the coding region for a fusion protein of tau and green fluorescent protein (tauGFP) replaces the first exon of the Itpr3 gene. We provide immunohistochemical and functional characterization of the cells expressing IP3 receptor type 3 in the olfactory epithelium. Since we determined that these cells bear microvilli at their apex, we call these cells IP3R3 MV cells. The cell body of these IP3R3 MV cells lies in the upper third of the main olfactory epithelium; a long thick basal process projects towards the base of the epithelium without penetrating the basal lamina. Retrograde labeling and unilateral bulbectomy corroborated that these IP3R3 MV cells do not extend axons to the olfactory bulb and therefore are not olfactory sensory neurons. The immunohistochemical features of the IP3R3 MV cell varied suggesting either developmental stages or the existence of subsets of these cells. Thus, for example, subsets of the IP3R3 MV cells make contact with substance P fibers or express the purinergic receptor P2X3. In addition, in recordings of intracellular calcium, these cells respond to ATP and substance P as well as to a variety of odors. The characterization of IP3R3 MV cells as non-neuronal chemoresponsive cells helps explain the differing descriptions of microvillous cells in the literature. PMID:20958798

  19. Response of the hammerhead shark olfactory epithelium to amino acid stimuli.

    PubMed

    Tricas, Timothy C; Kajiura, Stephen M; Summers, Adam P

    2009-10-01

    Sharks and rays are highly sensitive to chemical stimuli in their natural environment but several hypotheses predict that hammerhead sharks, with their expanded head and enlarged olfactory epithelium, have particularly acute olfactory systems. We used the electro-olfactogram (EOG) technique to compare the relative response of the scalloped hammerhead shark (Sphyrna lewini) olfactory epithelium to 20 proteinogenic amino acids and determine the sensitivity for 6 amino acids. At micromolar concentrations, cysteine evoked the greatest EOG response which was approximately twice as large as that of alanine. The weakest response was obtained for proline followed by aspartic acid and isoleucine. The olfactory epithelium showed adaptation to sequential stimulation, and recovery was related to the inter-stimulus time period. Estimated EOG response thresholds were in the sub-nanomolar range for both alanine (9.2 x 10(-11) M) and cysteine (8.4 x 10(-10) M) and in the micromolar range for proline and serine. These thresholds from 10(-10) to 10(-6) M for the scalloped hammerhead shark are comparable or lower than those reported for other teleost and elasmobranch species. Future work should focus on binary and more complex compounds to test for competition and cross-adaptation for different classes of peripheral receptors, and their responses to molecules found in biologically relevant stimuli.

  20. Adult Neurogenesis and the Olfactory System

    PubMed Central

    Whitman, Mary C.; Greer, Charles A.

    2009-01-01

    Though initially described in the early 1960s, it is only within the past decade that the concept of continuing adult neurogenesis has gained widespread acceptance. Neuroblasts from the subventricular zone (SVZ) migrate along the rostral migratory stream (RMS) into the olfactory bulb, where they differentiate into interneurons. Neuroblasts from the subgranular zone (SGZ) of the hippocampal formation show relatively little migratory behavior, and differentiate into dentate gyrus granule cells. In sharp contrast to embryonic and perinatal development, these newly differentiated neurons must integrate into a fully functional circuit, without disrupting ongoing performance. Here, after a brief historical overview and introduction to olfactory circuitry, we review recent advances in the biology of neural stem cells, mechanisms of migration in the RMS and olfactory bulb, differentiation and survival of new neurons, and finally mechanisms of synaptic integration. Our primary focus is on the olfactory system, but we also contrast the events occurring there with those in the hippocampal formation. Although both SVZ and SGZ neurogenesis are involved in some types of learning, their full functional significance remains unclear. Since both systems offer models of integration of new neuroblasts, there is immense interest in using neural stem cells to replace neurons lost in injury or disease. Though many questions remain unanswered, new insights appear daily about adult neurogenesis, regulatory mechanisms, and the fates of the progeny. We discuss here some of the central features of these advances, as well as speculate on future research directions. PMID:19615423

  1. Canonical Wnt Signaling Drives Tumor-Like Lesions from Sox2-Positive Precursors of the Murine Olfactory Epithelium

    PubMed Central

    Engel, Nils W.; Neumann, Julia E.; Ahlfeld, Julia; Wefers, Annika K.; Merk, Daniel J.; Ohli, Jasmin

    2016-01-01

    Canonical Wnt signaling is known to promote proliferation of olfactory stem cells. In order to investigate the effects of a constitutive activation of Wnt signaling in Sox2-positive precursor cells of the olfactory epithelium, we used transgenic mice that allowed an inducible deletion of exon 3 of the Ctnnb1 gene, which is responsible for the phosphorylation and degradation of Ctnnb1 protein. After induction of aberrant Wnt activation by Ctnnb1 deletion at embryonic day 14, such mice developed tumor-like lesions in upper parts of the nasal cavity. We still observed areas of epithelial hyperplasia within the olfactory epithelium following early postnatal Wnt activation, but the olfactory epithelial architecture remained unaffected in most parts when Wnt was activated at postnatal day 21 or later. In summary, our results suggest an age-dependent tumorigenic potential of aberrant Wnt signaling in the olfactory epithelium of mice. PMID:27902722

  2. Gene Expression Profiles of Main Olfactory Epithelium in Adenylyl Cyclase 3 Knockout Mice

    PubMed Central

    Wang, Zhenshan; Zhou, Yanfen; Luo, Yingtao; Zhang, Jing; Zhai, Yunpeng; Yang, Dong; Zhang, Zhe; Li, Yongchao; Storm, Daniel R.; Ma, Runlin Z.

    2015-01-01

    Adenylyl Cyclase 3 (AC3) plays an important role in the olfactory sensation-signaling pathway in mice. AC3 deficiency leads to defects in olfaction. However, it is still unknown whether AC3 deficiency affects gene expression or olfactory signal transduction pathways within the main olfactory epithelium (MOE). In this study, gene microarrays were used to screen differentially expressed genes in MOE from AC3 knockout (AC3−/−) and wild-type (AC3+/+) mice. The differentially expressed genes identified were subjected to bioinformatic analysis and verified by qRT-PCR. Gene expression in the MOE from AC3−/− mice was significantly altered, compared to AC3+/+ mice. Of the 41266 gene probes, 3379 had greater than 2-fold fold change in expression levels between AC3−/− and AC3+/+ mice, accounting for 8% of the total gene probes. Of these genes, 1391 were up regulated, and 1988 were down regulated, including 425 olfactory receptor genes, 99 genes that are specifically expressed in the immature olfactory neurons, 305 genes that are specifically expressed in the mature olfactory neurons, and 155 genes that are involved in epigenetic regulation. Quantitative RT-PCR verification of the differentially expressed epigenetic regulation related genes, olfactory receptors, ion transporter related genes, neuron development and differentiation related genes, lipid metabolism and membrane protein transport etc. related genes showed that P75NTR, Hinfp, Gadd45b, and Tet3 were significantly up-regulated, while Olfr370, Olfr1414, Olfr1208, Golf, Faim2, Tsg101, Mapk10, Actl6b, H2BE, ATF5, Kirrrel2, OMP, Drd2 etc. were significantly down-regulated. In summary, AC3 may play a role in proximal olfactory signaling and play a role in the regulation of differentially expressed genes in mouse MOE. PMID:26633363

  3. Exposure to Zinc Sulfate Results in Differential Effects on Olfactory Sensory Neuron Subtypes in Adult Zebrafish

    PubMed Central

    Hentig, James T.; Byrd-Jacobs, Christine A.

    2016-01-01

    Zinc sulfate is a known olfactory toxicant, although its specific effects on the olfactory epithelium of zebrafish are unknown. Olfactory organs of adult zebrafish were exposed to zinc sulfate and, after 2, 3, 5, 7, 10 or 14 days, fish were processed for histological, immunohistochemical, ultrastructural, and behavioral analyses. Severe morphological disruption of the olfactory organ was observed two days following zinc sulfate exposure, including fusion of lamellae, epithelial inflammation, and significant loss of anti-calretinin labeling. Scanning electron microscopy revealed the apical surface of the sensory region was absent of ciliated structures, but microvilli were still present. Behavioral analysis showed significant loss of the ability to perceive bile salts and some fish also had no response to amino acids. Over the next several days, olfactory organ morphology, epithelial structure, and anti-calretinin labeling returned to control-like conditions, although the ability to perceive bile salts remained lost until day 14. Thus, exposure to zinc sulfate results in rapid degeneration of the olfactory organ, followed by restoration of morphology and function within two weeks. Zinc sulfate appears to have a greater effect on ciliated olfactory sensory neurons than on microvillous olfactory sensory neurons, suggesting differential effects on sensory neuron subtypes. PMID:27589738

  4. Identification and molecular regulation of neural stem cells in the olfactory epithelium

    SciTech Connect

    Beites, Crestina L.; Kawauchi, Shimako; Crocker, Candice E.; Calof, Anne L. . E-mail: alcalof@uci.edu

    2005-06-10

    The sensory neurons that subserve olfaction, olfactory receptor neurons (ORNs), are regenerated throughout life, making the neuroepithelium in which they reside [the olfactory epithelium (OE)] an excellent model for studying how intrinsic and extrinsic factors regulate stem cell dynamics and neurogenesis during development and regeneration. Numerous studies indicate that transcription factors and signaling molecules together regulate generation of ORNs from stem and progenitor cells during development, and work on regenerative neurogenesis indicates that these same factors may operate at postnatal ages as well. This review describes our current knowledge of the identity of the OE neural stem cell; the different cell types that are thought to be the progeny (directly or indirectly) of this stem cell; and the factors that influence cell differentiation in the OE neuronal lineage. We review data suggesting that (1) the ORN lineage contains three distinct proliferating cell types-a stem cell and two populations of transit amplifying cells; (2) in established OE, these three cell types are present within the basal cell compartment of the epithelium; and (3) the stem cell that gives rise ultimately to ORNs may also generate two glial cell types of the primary olfactory pathway: sustentacular cells (SUS), which lie within OE proper; and olfactory ensheathing cells (OEC), which envelope the olfactory nerve. In addition, we describe factors that are both made by and found within the microenvironment of OE stem and progenitor cells, and which exert crucial growth regulatory effects on these cells. Thus, as with other regenerating tissues, the basis of regeneration in the OE appears be a population of stem cells, which resides within a microenvironment (niche) consisting of factors crucial for maintenance of its capacity for proliferation and differentiation.

  5. Nanoscale Particulate Matter from Urban Traffic Rapidly Induces Oxidative Stress and Inflammation in Olfactory Epithelium with Concomitant Effects on Brain

    PubMed Central

    Cheng, Hank; Saffari, Arian; Sioutas, Constantinos; Forman, Henry J.; Morgan, Todd E.; Finch, Caleb E.

    2016-01-01

    Background: Rodent models for urban air pollution show consistent induction of inflammatory responses in major brain regions. However, the initial impact of air pollution particulate material on olfactory gateways has not been reported. Objective: We evaluated the olfactory neuroepithelium (OE) and brain regional responses to a nanosized subfraction of urban traffic ultrafine particulate matter (nPM, < 200 nm) in vivo, ex vivo, and in vitro. Methods: Adult mice were exposed to reaerosolized nPM for 5, 20, and 45 cumulative hours over 3 weeks. The OE, the olfactory bulb (OB), the cerebral cortex, and the cerebellum were analyzed for oxidative stress and inflammatory responses. Acute responses of the OE to liquid nPM suspensions were studied with ex vivo and primary OE cultures. Results: After exposure to nPM, the OE and OB had rapid increases of 4-hydroxy-2-nonenal (4-HNE) and 3-nitrotyrosine (3-NT) protein adducts, whereas the cerebral cortex and cerebellum did not respond at any time. All brain regions showed increased levels of tumor necrosis factor-α (TNFα) protein by 45 hr, with earlier induction of TNFα mRNA in OE and OB. These responses corresponded to in vitro OE and mixed glial responses, with rapid induction of nitrite and inducible nitric oxide synthase (iNOS), followed by induction of TNFα. Conclusions: These findings show the differential time course of oxidative stress and inflammatory responses to nPM between the OE and the brain. Slow cumulative transport of inhaled nPM into the brain may contribute to delayed responses of proximal and distal brain regions, with potential input from systemic factors. Citation: Cheng H, Saffari A, Sioutas C, Forman HJ, Morgan TE, Finch CE. 2016. Nanoscale particulate matter from urban traffic rapidly induces oxidative stress and inflammation in olfactory epithelium with concomitant effects on brain. Environ Health Perspect 124:1537–1546; http://dx.doi.org/10.1289/EHP134 PMID:27187980

  6. Skn-1a/Pou2f3 is required for the generation of Trpm5-expressing microvillous cells in the mouse main olfactory epithelium

    PubMed Central

    2014-01-01

    Background The main olfactory epithelium (MOE) in mammals is a specialized organ to detect odorous molecules in the external environment. The MOE consists of four types of cells: olfactory sensory neurons, supporting cells, basal cells, and microvillous cells. Among these, development and function of microvillous cells remain largely unknown. Recent studies have shown that a population of microvillous cells expresses the monovalent cation channel Trpm5 (transient receptor potential channel M5). To examine functional differentiation of Trpm5-expressing microvillous cells in the MOE, we investigated the expression and function of Skn-1a, a POU (Pit-Oct-Unc) transcription factor required for functional differentiation of Trpm5-expressing sweet, umami, and bitter taste bud cells in oropharyngeal epithelium and solitary chemosensory cells in nasal respiratory epithelium. Results Skn-1a is expressed in a subset of basal cells and apical non-neuronal cells in the MOE of embryonic and adult mice. Two-color in situ hybridization revealed that a small population of Skn-1a-expressing cells was co-labeled with Mash1/Ascl1 and that most Skn-1a-expressing cells coexpress Trpm5. To investigate whether Skn-1a has an irreplaceable role in the MOE, we analyzed Skn-1a-deficient mice. In the absence of Skn-1a, olfactory sensory neurons differentiate normally except for a limited defect in terminal differentiation in ectoturbinate 2 of some of MOEs examined. In contrast, the impact of Skn-1a deficiency on Trpm5-expressing microvillous cells is much more striking: Trpm5, villin, and choline acetyltransferase, cell markers previously shown to identify Trpm5-expressing microvillous cells, were no longer detectable in Skn-1a-deficient mice. In addition, quantitative analysis demonstrated that the density of superficial microvillous cells was significantly decreased in Skn-1a-deficient mice. Conclusion Skn-1a is expressed in a minority of Mash1-positive olfactory progenitor cells and a

  7. Adult c-Kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons.

    PubMed

    Goldstein, Bradley J; Goss, Garrett M; Hatzistergos, Konstantinos E; Rangel, Erika B; Seidler, Barbara; Saur, Dieter; Hare, Joshua M

    2015-01-01

    The olfactory epithelium houses chemosensory neurons, which transmit odor information from the nose to the brain. In adult mammals, the olfactory epithelium is a uniquely robust neuroproliferative zone, with the ability to replenish its neuronal and non-neuronal populations due to the presence of germinal basal cells. The stem and progenitor cells of these germinal layers, and their regulatory mechanisms, remain incompletely defined. Here we show that progenitor cells expressing c-Kit, a receptor tyrosine kinase marking stem cells in a variety of embryonic tissues, are required for maintenance of the adult neuroepithelium. Mouse genetic fate-mapping analyses show that embryonically, a c-Kit(+) population contributes to olfactory neurogenesis. In adults under conditions of normal turnover, there is relatively sparse c-Kit(+) progenitor cell (ckPC) activity. However, after experimentally induced neuroepithelial injury, ckPCs are activated such that they reconstitute the neuronal population. There are also occasional non-neuronal cells found to arise from ckPCs. Moreover, the selective depletion of the ckPC population, utilizing temporally controlled targeted diphtheria toxin A expression, results in failure of neurogenesis after experimental injury. Analysis of this model indicates that most ckPCs reside among the globose basal cell populations and act downstream of horizontal basal cells, which can serve as stem cells. Identification of the requirement for olfactory c-Kit-expressing progenitors in olfactory maintenance provides new insight into the mechanisms involved in adult olfactory neurogenesis. Additionally, we define an important and previously unrecognized site of adult c-Kit activity.

  8. Intracellular injection of vital dyes into single cells in the salamander olfactory epithelium.

    PubMed

    Schwartz Levey, M; Cinelli, A R; Kauer, J S

    1992-06-22

    Intracellular vital dye injection was used to examine the morphology of single sustentacular and receptor cells and the developmental fate of individual basal cells in the olfactory epithelium of the tiger salamander. In acute experiments, Lucifer yellow injections were used to identify single basal, receptor or sustentacular cells on the basis of their overall morphology. Dye-coupling between a number of the different epithelial cells was observed. Progeny of basal cells were examined by following labeled cells for up to 2 weeks using intracellular injection of rhodamine-labeled dextran. These experiments indicate that some olfactory epithelial cells are dye-coupled and that dye-filled basal cells can undergo division and migration.

  9. Mercuric chloride induced toxicity responses in the olfactory epithelium of Labeo rohita (Hamilton): a light and electron microscopy study.

    PubMed

    Ghosh, Debasree; Mandal, Dipak Kumar

    2014-02-01

    Bioaccumulation of mercury and histomorphological changes in the olfactory epithelium of Labeo rohita were investigated after exposing the fish to two sublethal concentrations of HgCl₂ (66 and 132 μg/L) for 15 and 30 days. Mercury deposition increased in the tissue significantly (p < 0.05) with dose- and duration-dependent manner. Severe damage to the olfactory epithelium was evident. When fish exposed to 66 μg/L for 15 days, the histology of olfactory epithelium exhibited that mucous cell proliferation was upregulated and cell size was significantly increased from the control. Similar trends were found in 30 days exposure in both treated groups. Histology showed that mercury induced degeneration of columnar sensory cells, supporting cells and ciliated non-sensory cells and induced basal cell proliferation. Basal cell hyperplasia led to form intraepithelial proliferative lesion, thickening of epithelium, basal lamina disruption and cyst formation. Scanning electron microscopy revealed that mercury exposure at 66 μg/L caused clumping and loss of cilia, erosion in microridges on the supporting cells and proliferation of mucous cell opening. Complete degeneration of ciliated cells and cyst formation was observed in the fish when exposed to 132 μg/L HgCl₂. This result suggests that prolonged exposure to mercury might cause irreversible damage to the olfactory epithelium and impair the olfactory function of fish.

  10. Occurrence of neuropeptides and tyrosine hydroxylase in the olfactory epithelium of the lesser-spotted catshark (Scyliorhinus canicula Linnaeus, 1758).

    PubMed

    Zaccone, Daniele; Lo Cascio, Patrizia; Lauriano, Rita; Pergolizzi, Simona; Sfacteria, Alessandra; Marino, Fabio

    2011-11-01

    Immunohistochemical studies using antisera against various neuropeptides (Substance P, vasoactive intestinal polypeptide, and cholecystokinin octapeptide) and tyrosine hydroxylase revealed both olfactory sensory neuron (OSN) polymorphisms and transepithelial-subepithelial nerves in the olfactory epithelium of the cartilaginous fish, Scyliorhinus canicula. This study provides the first evidence of three morphological types of OSNs within the olfactory epithelium of cartilaginous fish that are similar to those found in the teleosts. In fishes there is evidence that OSNs differ functionally, including their differential olfactory bulb projections and molecular properties. The Substance P positive olfactory neurons in S. canicula may have a separate bulbar projection site that is not known, but may indicate a characteristic found in olfactory neuron subtypes in both lampreys and teleost fish. Numerous Substance P immunopositive nerves are found at the base of and in the olfactory epithelium. Some of them were observed to extend outwards almost reaching the epithelial surface. Their presumptive origin from the trigeminal nerve and their interrelationship with chemosensory cells in the nasal passages of vertebrates are discussed.

  11. Functional promiscuity in a mammalian chemosensory system: extensive expression of vomeronasal receptors in the main olfactory epithelium of mouse lemurs

    PubMed Central

    Hohenbrink, Philipp; Dempewolf, Silke; Zimmermann, Elke; Mundy, Nicholas I.; Radespiel, Ute

    2014-01-01

    The vomeronasal organ (VNO) is functional in most terrestrial mammals, though progressively reduced in the primate lineage, and is used for intraspecific communication and predator recognition. Vomeronasal receptor (VR) genes comprise two families of chemosensory genes (V1R and V2R) that have been considered to be specific for the VNO. However, recently a large number of VRs were reported to be expressed in the main olfactory epithelium (MOE) of mice, but there is little knowledge of the expression of these genes outside of rodents. To explore the function of VR genes in mammalian evolution, we analyzed and compared the expression of 64 V1R and 2 V2R genes in the VNO and the MOE of the gray mouse lemur (Microcebus murinus), the primate with the largest known VR repertoire. We furthermore compared expression patterns in adults of both sexes and seasons, and in an infant. A large proportion (83–97%) of the VR loci was expressed in the VNO of all individuals. The repertoire in the infant was as rich as in adults, indicating reliance on olfactory communication from early postnatal development onwards. In concordance with mice, we also detected extensive expression of VRs in the MOE, with proportions of expressed loci in individuals ranging from 29 to 45%. TRPC2, which encodes a channel protein crucial for signal transduction via VRs, was co-expressed in the MOE in all individuals indicating likely functionality of expressed VR genes in the MOE. In summary, the large VR repertoire in mouse lemurs seems to be highly functional. Given the differences in the neural pathways of MOE and VNO signals, which project to higher cortical brain centers or the limbic system, respectively, this raises the intriguing possibility that the evolution of MOE-expression of VRs enabled mouse lemurs to adaptively diversify the processing of VR-encoded olfactory information. PMID:25309343

  12. Purinergic Receptor Antagonists Inhibit Odorant-Induced Heat Shock Protein 25 Induction in Mouse Olfactory Epithelium

    PubMed Central

    Hegg, Colleen C.; Lucero, Mary T.

    2010-01-01

    Heat shock proteins (HSPs) accumulate in cells exposed to a variety of physiological and environmental factors, such as heat shock, oxidative stress, toxicants, and odorants. Ischemic, stressed, and injured cells release ATP in large amounts. Our hypothesis is that noxious stimulation (in this case, strong odorant) evokes the release of ATP in the olfactory epithelium (OE). Extracellular ATP, a signal of cellular stress, induces the expression of HSPs via purinergic receptors. In the present study, in vivo odorant exposure (heptanal or r-carvone) led to a selective induction of HSP25 in glia-like sustentacular cells in the Swiss Webster mouse OE, as previously shown in rats (Carr et al., 2001). Furthermore, in vitro and in vivo administration of purinergic receptor antagonists suramin and pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) blocked the expression of HSP25 immunoreactivity in sustentacular cells. ATP released by acutely injured cells could act as an early signal of cell and tissue damage, causing HSP expression and initiating a stress signaling cascade to protect against further damage. Sustentacular cells have a high capacity to detoxify xenobiotics and thereby protect the olfactory epithelium from airborne pollutants. Thus, the robust, rapid induction of HSPs in sustentacular cells may help maintain the integrity of the OE during exposure to toxicants. PMID:16206165

  13. Anatomical and functional evidence for a role of arginine-vasopressin (AVP) in rat olfactory epithelium cells.

    PubMed

    Levasseur, Grégoire; Baly, Christine; Grébert, Denise; Durieux, Didier; Salesse, Roland; Caillol, Monique

    2004-08-01

    The olfactory epithelium (OE) is composed of olfactory sensory neurons (OSNs) and sustentacular cells; it lies in the nasal cavity where it is protected by a thin mucus layer. The finely regulated composition of this mucus provides OSN with a suitable ionic environment. To maintain the functional integrity of the epithelium despite permanent physical, chemical and microbial aggressions, both OSNs and surrounding sustentacular cells are continuously renewed from globose basal cells. Moreover, the sense of smell is involved in so numerous behaviours (feeding, reproduction, etc.) that it has to cross-talk with the endocrine and neuroendocrine systems. Thus, besides its sensory function, the olfactory epithelium is thought to undergo a lot of complex regulatory processes. We therefore studied the effects of various neuropeptides on primary cultures of Sprague-Dawley rat olfactory epithelium cells. We found that arginine-vasopressin (AVP) triggered a robust, dose-dependent calcium increase in these cells. The cell response was essentially ascribed to the V1a AVP receptor, whose presence was confirmed by RT-PCR and immunolabelling. In the culture, V1a but not V1b receptors were present, mainly localized in neurons. In the epithelium, both subtypes were found differentially distributed. V1a-R were localized mainly in globose basal cells and at the apical side of the epithelium, in the area of the dendritic knobs of OSNs. V1b-R were strongly associated with Bowman's gland cells and globose basal cells. These localizations suggested potential multifaceted roles of a hormone, AVP, in the olfactory epithelium.

  14. Sensory deprivation disrupts homeostatic regeneration of newly generated olfactory sensory neurons after injury in adult mice.

    PubMed

    Kikuta, Shu; Sakamoto, Takashi; Nagayama, Shin; Kanaya, Kaori; Kinoshita, Makoto; Kondo, Kenji; Tsunoda, Koichi; Mori, Kensaku; Yamasoba, Tatsuya

    2015-02-11

    Although it is well known that injury induces the generation of a substantial number of new olfactory sensory neurons (OSNs) in the adult olfactory epithelium (OE), it is not well understood whether olfactory sensory input influences the survival and maturation of these injury-induced OSNs in adults. Here, we investigated whether olfactory sensory deprivation affected the dynamic incorporation of newly generated OSNs 3, 7, 14, and 28 d after injury in adult mice. Mice were unilaterally deprived of olfactory sensory input by inserting a silicone tube into their nostrils. Methimazole, an olfactotoxic drug, was also injected intraperitoneally to bilaterally ablate OSNs. The OE was restored to its preinjury condition with new OSNs by day 28. No significant differences in the numbers of olfactory marker protein-positive mature OSNs or apoptotic OSNs were observed between the deprived and nondeprived sides 0-7 d after injury. However, between days 7 and 28, the sensory-deprived side showed markedly fewer OSNs and mature OSNs, but more apoptotic OSNs, than the nondeprived side. Intrinsic functional imaging of the dorsal surface of the olfactory bulb at day 28 revealed that responses to odor stimulation were weaker in the deprived side compared with those in the nondeprived side. Furthermore, prevention of cell death in new neurons 7-14 d after injury promoted the recovery of the OE. These results indicate that, in the adult OE, sensory deprivation disrupts compensatory OSN regeneration after injury and that newly generated OSNs have a critical time window for sensory-input-dependent survival 7-14 d after injury.

  15. Responses of round goby (Neogobius melanostomus) olfactory epithelium to steroids released by reproductive males.

    PubMed

    Laframboise, Alyson J; Zielinski, Barbara S

    2011-10-01

    The wild perciform teleost Neogobius melanostomus (the round goby) originated from the Ponto-Caspian region and is now a highly successful invasive species in the Laurentian Great Lakes. Males may attract females into their nests for spawning by releasing reproductive pheromones, and it has been previously shown that reproductive males synthesize and release the 5β-reduced and 3α-hydroxyl steroids 3α-hydroxy-5β-androstane-11,17-dione (11-oxo-etiocholanolone; 11-O-ETIO) and 3α-hydroxy-5β-androstane-11,17-dione 3-sulfate (11-oxo-etiocholanolone-3-sulfate; 11-O-ETIO-3-s) and 3α,17β-dihydroxy-5β-androstan-11-one 17-sulfate. In this study, we investigated properties of these released steroids by recording field potential responses from the olfactory epithelium (electro-olfactogram, EOG). The steroid 3α,17β-dihydroxy-5β-androstan-11-one 17-sulfate did not elicit olfactory responses while both 11-O-ETIO and 11-O-ETIO-3-s stimulated olfactory field potentials in the round goby, but not in the goldfish. Cross-adaptation analysis demonstrated that round gobies discriminated between11-O-ETIO and 11-O-ETIO-3-s (as well as etiocholanolone, ETIO) at the sensory level. Second messenger cascades depending on both cAMP and IP(3) were inferred for steroids from pharmacological inhibition studies, while the canonical teleost odors taurocholic acid (a bile acid) and L: -alanine (an amino acid) used only cAMP and IP(3), respectively. The round goby presents itself as an excellent species for the study of olfactory function of fish in the wild, given its possible use of these released steroids as pheromones.

  16. Terminal nerve-derived neuropeptide y modulates physiological responses in the olfactory epithelium of hungry axolotls (Ambystoma mexicanum).

    PubMed

    Mousley, Angela; Polese, Gianluca; Marks, Nikki J; Eisthen, Heather L

    2006-07-19

    The vertebrate brain actively regulates incoming sensory information, effectively filtering input and focusing attention toward environmental stimuli that are most relevant to the animal's behavioral context or physiological state. Such centrifugal modulation has been shown to play an important role in processing in the retina and cochlea, but has received relatively little attention in olfaction. The terminal nerve, a cranial nerve that extends underneath the lamina propria surrounding the olfactory epithelium, displays anatomical and neurochemical characteristics that suggest that it modulates activity in the olfactory epithelium. Using immunocytochemical techniques, we demonstrate that neuropeptide Y (NPY) is abundantly present in the terminal nerve in the axolotl (Ambystoma mexicanum), an aquatic salamander. Because NPY plays an important role in regulating appetite and hunger in many vertebrates, we investigated the possibility that NPY modulates activity in the olfactory epithelium in relation to the animal's hunger level. We therefore characterized the full-length NPY gene from axolotls to enable synthesis of authentic axolotl NPY for use in electrophysiological experiments. We find that axolotl NPY modulates olfactory epithelial responses evoked by l-glutamic acid, a food-related odorant, but only in hungry animals. Similarly, whole-cell patch-clamp recordings demonstrate that bath application of axolotl NPY enhances the magnitude of a tetrodotoxin-sensitive inward current, but only in hungry animals. These results suggest that expression or activity of NPY receptors in the olfactory epithelium may change with hunger level, and that terminal nerve-derived peptides modulate activity in the olfactory epithelium in response to an animal's changing behavioral and physiological circumstances.

  17. Changes in the neural representation of odorants after olfactory deprivation in the adult mouse olfactory bulb.

    PubMed

    Kass, Marley D; Pottackal, Joseph; Turkel, Daniel J; McGann, John P

    2013-01-01

    Olfactory sensory deprivation during development has been shown to induce significant alterations in the neurophysiology of olfactory receptor neurons (ORNs), the primary sensory inputs to the brain's olfactory bulb. Deprivation has also been shown to alter the neurochemistry of the adult olfactory system, but the physiological consequences of these changes are poorly understood. Here we used in vivo synaptopHluorin (spH) imaging to visualize odorant-evoked neurotransmitter release from ORNs in adult transgenic mice that underwent 4 weeks of unilateral olfactory deprivation. Deprivation reduced odorant-evoked spH signals compared with sham-occluded mice. Unexpectedly, this reduction was equivalent between ORNs on the open and plugged sides. Changes in odorant selectivity of glomerular subpopulations of ORNs were also observed, but only in ORNs on the open side of deprived mice. These results suggest that naris occlusion in adult mice produces substantial changes in primary olfactory processing which may reflect not only the decrease in olfactory stimulation on the occluded side but also the alteration of response properties on the intact side. We also observed a modest effect of true sham occlusions that included noseplug insertion and removal, suggesting that conventional noseplug techniques may have physiological effects independent of deprivation per se and thus require more careful controls than has been previously appreciated.

  18. Apoptosis induced by prolonged exposure to odorants in cultured cells from rat olfactory epithelium.

    PubMed

    Brauchi, Sebastian; Cea, Christian; Farias, Jorge G; Bacigalupo, Juan; Reyes, Juan G

    2006-08-04

    Multicellular organisms undergo programmed cell death (PCD) as a mechanism for tissue remodeling during development and tissue renewal throughout adult life. Overdose of some neuronal receptor agonists like glutamate can trigger a PCD process termed excitotoxicity in neurons of the central nervous system. Calcium has an important role in PCD processes, especially in excitotoxicity. Since the normal turnover of olfactory receptor neurons (ORNs) relies, at least in part, on an apoptotic mechanism and odor transduction in ORNs involves an increase in intracellular Ca2+ concentration ([Ca2+]i), we investigated the possibility that long-term exposures to odorants could trigger an excitotoxic process in olfactory epithelial cells (EC). We used single-cell [Ca2+]i determinations and fluorescence microscopy techniques to study the effects of sustained odorant exposures in olfactory EC in primary culture. Induction of PCD was evaluated successively by three independent criteria: (1) measurements of DNA fragmentation, (2) translocation of phosphatidylserine to the external leaflet of the plasma membrane, and (3) caspase-3 activation. Our results support the notion of an odorant-induced PCD in olfactory EC. This odorant-induced PCD was prevented by LY83583, an odorant response inhibitor, suggesting that ORNs are the main epithelial cell population undergoing odorant-induced PCD.

  19. Genome-Wide Screen Reveals Rhythmic Regulation of Genes Involved in Odor Processing in the Olfactory Epithelium.

    PubMed

    Saleh, Manjana; Jürchott, Karsten; Oberland, Sonja; Neuhaus, Eva M; Kramer, Achim; Abraham, Ute

    2015-12-01

    Odor discrimination behavior displays circadian fluctuations in mice, indicating that mammalian olfactory function is under control of the circadian system. This is further supported by the facts that odor discrimination rhythms depend on the presence of clock genes and that olfactory tissues contain autonomous circadian clocks. However, the molecular link between circadian function and olfactory processing is still unknown. To elucidate the molecular mechanisms underlying this link, we focused on the olfactory epithelium (OE), the primary target of odors and the site of the initial events in olfactory processing. We asked whether olfactory sensory neurons (OSNs) within the OE possess an autonomous circadian clock and whether olfactory pathways are under circadian control. Employing clock gene-driven bioluminescence reporter assays and time-dependent immunohistochemistry on OE samples, we found robust circadian rhythms of core clock genes and their proteins in OSNs, suggesting that the OE indeed contains an autonomous circadian clock. Furthermore, we performed a circadian transcriptome analysis and identified several OSN-specific components that are under circadian control, including those with putative roles in circadian olfactory processing, such as KIRREL2-an established factor involved in short-term OSN activation. The spatiotemporal expression patterns of our candidate proteins suggest that they are involved in short-term anabolic processes to rhythmically prepare the cell for peak performances and to promote circadian function of OSNs.

  20. The role of olfactory stimulus in adult mammalian neurogenesis.

    PubMed

    Arisi, Gabriel M; Foresti, Maira L; Mukherjee, Sanjib; Shapiro, Lee A

    2012-02-14

    Neurogenesis occurs in the adult mammalian brain in discrete regions related to olfactory sensory signaling and integration. The olfactory receptor cell population is in constant turn-over through local progenitor cells. Also, newborn neurons are added to the olfactory bulbs through a major migratory route from the subventricular zone, the rostral migratory stream. The olfactory bulbs project to different brain structures, including: piriform cortex, amygdala, entorhinal cortex, striatum and hippocampus. These structures play important roles in odor identification, feeding behavior, social interactions, reproductive behavior, behavioral reinforcement, emotional responses, learning and memory. In all of these regions neurogenesis has been described in normal and in manipulated mammalian brain. These data are reviewed in the context of a sensory-behavioral hypothesis on adult neurogenesis that olfactory input modulates neurogenesis in many different regions of the brain.

  1. Response of olfactory axons to loss of synaptic targets in the adult mouse

    PubMed Central

    Ardiles, Yona; de la Puente, Rafael; Toledo, Rafael; Isgor, Ceylan; Guthrie, Kathleen

    2007-01-01

    Glomerular convergence has been proposed to rely on interactions between like olfactory axons, however topographic targeting is influenced by guidance molecules encountered in the olfactory bulb. Disruption of these cues during development misdirects sensory axons, however little is known about the role of bulb-derived signals in later life, as new axons arise during turnover of the olfactory sensory neuron (OSN) population. To evaluate the contribution of bulb neurons in maintaining topographic projections in adults, we ablated them with N-methyl-D-aspartate (NMDA) in P2-IRES-tauLacZ mice and examined how sensory axons responded to loss of their postsynaptic partners. NMDA lesion eliminated bulb neurons without damage to sensory axons or olfactory ensheathing glia. P2 axons contained within glomeruli at the time of lesion maintained convergence at these locations; there was no evidence of compensatory growth into the remnant tissue. Delayed apoptosis of OSNs in the target-deprived epithelium led to declines in P2 neuron number as well as the gradual atrophy, and in some cases complete loss, of P2 glomeruli in lesioned bulbs by three weeks. Increased cell proliferation in the epithelium partially restored the OSN population, and by eight weeks, new P2 axons distributed within diverse locations in the bulb remnant and within the anterior olfactory nucleus. Prior studies have suggested that initial development of olfactory topography does not rely on synapse formation with target neurons, however the present data demonstrate that continued maintenance of the sensory map requires the presence of sufficient numbers and/or types of available bulbar synaptic targets. PMID:17674970

  2. Synergistic action of nectins and cadherins generates the mosaic cellular pattern of the olfactory epithelium

    PubMed Central

    Katsunuma, Sayaka; Honda, Hisao; Shinoda, Tomoyasu; Ishimoto, Yukitaka; Miyata, Takaki; Kiyonari, Hiroshi; Abe, Takaya; Nibu, Ken-ichi; Takai, Yoshimi

    2016-01-01

    In the olfactory epithelium (OE), olfactory cells (OCs) and supporting cells (SCs), which express different cadherins, are arranged in a characteristic mosaic pattern in which OCs are enclosed by SCs. However, the mechanism underlying this cellular patterning is unclear. Here, we show that the cellular pattern of the OE is established by cellular rearrangements during development. In the OE, OCs express nectin-2 and N-cadherin, and SCs express nectin-2, nectin-3, E-cadherin, and N-cadherin. Heterophilic trans-interaction between nectin-2 on OCs and nectin-3 on SCs preferentially recruits cadherin via α-catenin to heterotypic junctions, and the differential distributions of cadherins between junctions promote cellular intercalations, resulting in the formation of the mosaic pattern. These observations are confirmed by model cell systems, and various cellular patterns are generated by the combinatorial expression of nectins and cadherins. Collectively, the synergistic action of nectins and cadherins generates mosaic pattern, which cannot be achieved by a single mechanism. PMID:26929452

  3. Transcription factor p63 controls the reserve status but not the stemness of horizontal basal cells in the olfactory epithelium

    PubMed Central

    Schnittke, Nikolai; Herrick, Daniel B.; Lin, Brian; Peterson, Jesse; Coleman, Julie H.; Packard, Adam I.; Jang, Woochan; Schwob, James E.

    2015-01-01

    Adult tissue stem cells can serve two broad functions: to participate actively in the maintenance and regeneration of a tissue or to wait in reserve and participate only when activated from a dormant state. The adult olfactory epithelium, a site for ongoing, life-long, robust neurogenesis, contains both of these functional stem cell types. Globose basal cells (GBCs) act as the active stem cell population and can give rise to all the differentiated cells found in the normal tissue. Horizontal basal cells (HBCs) act as reserve stem cells and remain dormant unless activated by tissue injury. Here we show that HBC activation following injury by the olfactotoxic gas methyl bromide is coincident with the down-regulation of protein 63 (p63) but anticipates HBC proliferation. Gain- and loss-of-function studies show that this down-regulation of p63 is necessary and sufficient for HBC activation. Moreover, activated HBCs give rise to GBCs that persist for months and continue to act as bona fide stem cells by participating in tissue maintenance and regeneration over the long term. Our analysis provides mechanistic insight into the dynamics between tissue stem cell subtypes and demonstrates that p63 regulates the reserve state but not the stem cell status of HBCs. PMID:26305958

  4. Stem and progenitor cells of the mammalian olfactory epithelium: Taking poietic license.

    PubMed

    Schwob, James E; Jang, Woochan; Holbrook, Eric H; Lin, Brian; Herrick, Daniel B; Peterson, Jesse N; Hewitt Coleman, Julie

    2017-03-01

    The capacity of the olfactory epithelium (OE) for lifelong neurogenesis and regeneration depends on the persistence of neurocompetent stem cells, which self-renew as well as generating all of the cell types found within the nasal epithelium. This Review focuses on the types of stem and progenitor cells in the epithelium and their regulation. Both horizontal basal cells (HBCs) and some among the population of globose basal cells (GBCs) are stem cells, but the two types plays vastly different roles. The GBC population includes the basal cells that proliferate in the uninjured OE and is heterogeneous with respect to transcription factor expression. From upstream in the hierarchy to downstream, GBCs encompass 1) Sox2(+) /Pax6(+) stem-like cells that are totipotent and self-renew over the long term, 2) Ascl1(+) transit-amplifying progenitors with a limited capacity for expansive proliferation, and 3) Neurog1(+) /NeuroD1(+) immediate precursor cells that make neurons directly. In contrast, the normally quiescent HBCs are activated to multipotency and proliferate when sustentacular cells are killed, but not when only OSNs die, indicating that HBCs are reserve stem cells that respond to severe epithelial injury. The master regulator of HBC activation is the ΔN isoform of the transcription factor p63; eliminating ΔNp63 unleashes HBC multipotency. Notch signaling, via Jagged1 ligand on Sus cells and Notch1 and Notch2 receptors on HBCs, is likely to play a major role in setting the level of p63 expression. Thus, ΔNp63 becomes a potential therapeutic target for reversing the neurogenic exhaustion characteristic of the aged OE. J. Comp. Neurol. 525:1034-1054, 2017. © 2016 Wiley Periodicals, Inc.

  5. Olfactory Behavioral Testing in the Adult Mouse

    PubMed Central

    M. Witt, Rochelle; M. Galligan, Meghan; R. Despinoy, Jennifer; Segal, Rosalind

    2009-01-01

    The rodent olfactory system is of increasing interest to scientists, studied, in part, in systems biology because of its stereotyped, yet accessible circuitry. In addition, this area's unique ability to generate new neurons throughout an organism's lifetime makes it an attractive system for developmental and regenerative biologists alike. Such interest necessitates a means for a quick, yet reliable assessment of olfactory function. Many tests of olfactory ability are complex, variable or not specifically designed for mice. Also, some tests are sensitive to memory deficits as well as defects in olfactory abilities, confounding obtained results. Here, we describe a simple battery of tests designed to identify defects in olfactory sensitivity and preference. First, an initial general health assessment allows for the identification of animals suitable for further testing. Second, mice are exposed to various dilutions of scents to ascertain whether there is a threshold difference. Third, mice are presented with various scents, both attractive and aversive, that allow for the assessment of olfactory preference. These simple studies should make the initial characterization of olfactory behavior accessible for labs of varied resources and expertise. PMID:19229182

  6. Olfactory behavioral testing in the adult mouse.

    PubMed

    Witt, Rochelle M; Galligan, Meghan M; Despinoy, Jennifer R; Segal, Rosalind

    2009-01-28

    The rodent olfactory system is of increasing interest to scientists, studied, in part, in systems biology because of its stereotyped, yet accessible circuitry. In addition, this area's unique ability to generate new neurons throughout an organism's lifetime makes it an attractive system for developmental and regenerative biologists alike. Such interest necessitates a means for a quick, yet reliable assessment of olfactory function. Many tests of olfactory ability are complex, variable or not specifically designed for mice. Also, some tests are sensitive to memory deficits as well as defects in olfactory abilities, confounding obtained results. Here, we describe a simple battery of tests designed to identify defects in olfactory sensitivity and preference. First, an initial general health assessment allows for the identification of animals suitable for further testing. Second, mice are exposed to various dilutions of scents to ascertain whether there is a threshold difference. Third, mice are presented with various scents, both attractive and aversive, that allow for the assessment of olfactory preference. These simple studies should make the initial characterization of olfactory behavior accessible for labs of varied resources and expertise.

  7. Development of the main olfactory system and main olfactory epithelium-dependent male mating behavior are altered in Go-deficient mice.

    PubMed

    Choi, Jung-Mi; Kim, Sung-Soo; Choi, Chan-Il; Cha, Hye Lim; Oh, Huy-Hyen; Ghil, Sungho; Lee, Young-Don; Birnbaumer, Lutz; Suh-Kim, Haeyoung

    2016-09-27

    In mammals, initial detection of olfactory stimuli is mediated by sensory neurons in the main olfactory epithelium (MOE) and the vomeronasal organ (VNO). The heterotrimeric GTP-binding protein Go is widely expressed in the MOE and VNO of mice. Early studies indicated that Go expression in VNO sensory neurons is critical for directing social and sexual behaviors in female mice [Oboti L, et al. (2014) BMC Biol 12:31]. However, the physiological functions of Go in the MOE have remained poorly defined. Here, we examined the role of Go in the MOE using mice lacking the α subunit of Go Development of the olfactory bulb (OB) was perturbed in mutant mice as a result of reduced neurogenesis and increased cell death. The balance between cell types of OB interneurons was altered in mutant mice, with an increase in the number of tyrosine hydroxylase-positive interneurons at the expense of calbindin-positive interneurons. Sexual behavior toward female mice and preference for female urine odors by olfactory sensory neurons in the MOE were abolished in mutant male mice. Our data suggest that Go signaling is essential for the structural and functional integrity of the MOE and for specification of OB interneurons, which in turn are required for the transmission of pheromone signals and the initiation of mating behavior with the opposite sex.

  8. Development of olfactory epithelium and associated structures in the green iguana, Iguana iguana—light and scanning electron microscopic study

    PubMed Central

    Cizek, Petr; Tichy, Frantisek

    2016-01-01

    The ontogenesis of the nasal cavity has been described in many mammalian species. The situation is different with reptiles, despite the fact that they have become relatively common as pets. In this study we focused on the ontogenesis of the olfactory epithelium, as well as other types of epithelia in the nasal cavity of pre-hatched green iguanas (Iguana iguana). Collection of samples began from day 67 of incubation and continued every four days until hatching. Microscopic examination revealed that significant morphological changes in the nasal cavity began approximately at day 91 of ontogenesis. Approximately at this same stage, the nasal cavity epithelium began to differentiate. The cavity was divided into two compartments by a cartilaginous disc. The ventral compartment bulged rostrally and eventually opened up into the external environment. Three clearly demarcated areas of epithelium in the nasal cavity were visible at day 107. PMID:27920949

  9. Development of olfactory epithelium and associated structures in the green iguana, Iguana iguana-light and scanning electron microscopic study.

    PubMed

    Sapoznikov, Olga; Cizek, Petr; Tichy, Frantisek

    2016-01-01

    The ontogenesis of the nasal cavity has been described in many mammalian species. The situation is different with reptiles, despite the fact that they have become relatively common as pets. In this study we focused on the ontogenesis of the olfactory epithelium, as well as other types of epithelia in the nasal cavity of pre-hatched green iguanas (Iguana iguana). Collection of samples began from day 67 of incubation and continued every four days until hatching. Microscopic examination revealed that significant morphological changes in the nasal cavity began approximately at day 91 of ontogenesis. Approximately at this same stage, the nasal cavity epithelium began to differentiate. The cavity was divided into two compartments by a cartilaginous disc. The ventral compartment bulged rostrally and eventually opened up into the external environment. Three clearly demarcated areas of epithelium in the nasal cavity were visible at day 107.

  10. Epithelium

    MedlinePlus

    The term "epithelium" refers to layers of cells that line hollow organs and glands. It is also those cells that make ... Epithelium. In: Kierszenbaum AL, Tres LL. Histology and Cell Biology - An Introduction to Pathology , 3rd ed. Philadelphia, ...

  11. Early Olfactory Environment Influences Social Behaviour in Adult Octodon degus

    PubMed Central

    Márquez, Natalia; Martínez-Harms, Jaime; Vásquez, Rodrigo A.; Mpodozis, Jorge

    2015-01-01

    We evaluated the extent to which manipulation of early olfactory environment can influence social behaviours in the South American Hystricognath rodent Octodon degus. The early olfactory environment of newborn degus was manipulated by scenting all litter members with eucalyptol during the first month of life. The social behaviour of sexually mature animals (5–7 months old) towards conspecifics was then assessed using a y-maze to compare the response of control (naïve) and treated animals to two different olfactory configurations (experiment 1): (i) a non-familiarized conspecific impregnated with eucalyptol (eucalyptol arm) presented against (ii) a non-familiarized unscented conspecific (control arm). In addition, in dyadic encounters, we assessed the behaviour of control and eucalyptol treated animals towards a non-familiarized conspecific scented with eucalyptol (experiment 2). We found that control subjects explored and spent significantly less time in the eucalyptol arm, indicating neophobic behaviours towards the artificially scented conspecific. Treated subjects explored and spent similar time in both arms of the maze, showing the same interest for both olfactory stimuli presented. During dyadic encounters in experiment 2, an interaction effect between early experience and sex was observed. Control males escaped and avoided their scented partner more frequently than eucalyptol treated male subjects and than females. Both groups did not differ in the exploration of their scented partners, suggesting that avoidance within agonistic context does not relate to neophobic behaviours. Our results suggest that the exposure to eucalyptol during early ontogeny decreases evasive behaviours within an agonistic context as a result of olfactory learning. Altogether, these results indicate that olfactory cues learned in early ontogeny can influence olfactory-guided behaviours in adult degus. PMID:25671542

  12. mSWI/SNF (BAF) Complexes Are Indispensable for the Neurogenesis and Development of Embryonic Olfactory Epithelium

    PubMed Central

    Pham, Linh; Rabe, Tamara; Sokpor, Godwin; Seong, Rho H.; Ashery-Padan, Ruth; Mansouri, Ahmed; Stoykova, Anastassia; Staiger, Jochen F.; Tuoc, Tran

    2016-01-01

    Neurogenesis is a key developmental event through which neurons are generated from neural stem/progenitor cells. Chromatin remodeling BAF (mSWI/SNF) complexes have been reported to play essential roles in the neurogenesis of the central nervous system. However, whether BAF complexes are required for neuron generation in the olfactory system is unknown. Here, we identified onscBAF and ornBAF complexes, which are specifically present in olfactory neural stem cells (oNSCs) and olfactory receptor neurons (ORNs), respectively. We demonstrated that BAF155 subunit is highly expressed in both oNSCs and ORNs, whereas high expression of BAF170 subunit is observed only in ORNs. We report that conditional deletion of BAF155, a core subunit in both onscBAF and ornBAF complexes, causes impaired proliferation of oNSCs as well as defective maturation and axonogenesis of ORNs in the developing olfactory epithelium (OE), while the high expression of BAF170 is important for maturation of ORNs. Interestingly, in the absence of BAF complexes in BAF155/BAF170 double-conditional knockout mice (dcKO), OE is not specified. Mechanistically, BAF complex is required for normal activation of Pax6-dependent transcriptional activity in stem cells/progenitors of the OE. Our findings unveil a novel mechanism mediated by the mSWI/SNF complex in OE neurogenesis and development. PMID:27611684

  13. Neuroblast long-term cell cultures from human fetal olfactory epithelium respond to odors.

    PubMed

    Vannelli, G B; Ensoli, F; Zonefrati, R; Kubota, Y; Arcangeli, A; Becchetti, A; Camici, G; Barni, T; Thiele, C J; Balboni, G C

    1995-06-01

    Primary cell cultures from human fetal olfactory neuroepithelium have been isolated, cloned, and propagated in continuous in vitro culture for approximately 1 year. The two clones we report here synthesize both neuronal proteins and olfactory-specific markers as well as the putative olfactory neurotransmitter, carnosine. In addition, patchclamp experiments reveal that these cells are electrically excitable. Following exposure to a panel of aromatic chemicals one of the cell cultures shows a specific increase in intracellular cAMP, indicating that some degree of functional maturity is expressed in vitro. The results suggest that these cells originate from the "stem cell" compartment that gives rise to mature olfactory receptor neurons. These long-term cell cultures represent models that will be useful in studying the mechanism(s) of olfaction and the regulation of olfactory neurogenesis and differentiation.

  14. Histological and electrophysiological properties of crypt cells from the olfactory epithelium of the marine teleost Trachurus symmetricus.

    PubMed

    Schmachtenberg, Oliver

    2006-03-01

    Crypt cells from the olfactory epithelium of the Pacific jack mackerel Trachurus symmetricus were characterized by light and electron microscopy and analyzed in dissociation with the patch-clamp technique in its cell-attached, perforated patch and normal whole-cell mode. Isolated crypt cells remained united with their supporting cells, and both were electrically coupled through gap junctions. Under voltage-clamp, depolarizing voltage steps triggered a transient sodium current, a sustained calcium current, and two types of potassium currents with fast and slow inactivation kinetics. No calcium-dependent potassium current could be observed. The sodium current was blocked by saxitoxin, the calcium current by cobalt and furnidipine, and the potassium currents by tetraethylammonium chloride. In the cell-attached configuration, crypt cells displayed spontaneous spike activity and responded to amino acid solutions with dose-dependent excitation, followed by a period of spike inhibition. These first recordings of individual crypt cells provide the basis for future studies of their odorant specificity, transduction mechanism, and overall function in the fish olfactory epithelium.

  15. Combinatorial analysis of calcium-binding proteins in larval and adult zebrafish primary olfactory system identifies differential olfactory bulb glomerular projection fields.

    PubMed

    Kress, Sigrid; Biechl, Daniela; Wullimann, Mario F

    2015-07-01

    In the zebrafish (Danio rerio) olfactory epithelium, the calcium-binding proteins (CBPs) calretinin and S100/S100-like protein are mainly expressed in ciliated or crypt olfactory sensory neurons (OSNs), respectively. In contrast parvalbumin and calbindin1 have not been investigated. We present a combinatorial immunohistological analysis of all four CBPs, including their expression in OSNs and their axonal projections to the olfactory bulb in larval and adult zebrafish. A major expression of calretinin and S100 in ciliated and crypt cells, respectively, with some expression of S100 in microvillous cells is confirmed. Parvalbumin and calbindin1 are strongly expressed in ciliated and microvillous cells, but not in crypt cells. Moreover, detailed combinatorial double-label experiments indicate that there are eight subpopulations of zebrafish OSNs: S100-positive crypt cells (negative for all other three CBPs), parvalbumin only, S100 and parvalbumin, parvalbumin and calbindin1, and parvalbumin and calbindin1 and calretinin-positive microvillous OSNs, as well as a major parvalbumin and calbindin1 and calretinin, and minor parvalbumin and calbindin1 and calretinin-only-positive ciliated OSN populations. CBP-positive projections to olfactory bulb are consistent with previous reports of ciliated OSNs projecting to dorsal and ventromedial glomerular fields and microvillous OSNs to ventrolateral glomerular fields. We newly describe parvalbumin-positive fibers to the mediodorsal field which is calretinin free, with its anterior part showing additionally calbindin1-positive fibers, but absence thereof in the posterior part, indicating an origin from microvillous OSNs in both parts. One singular glomerulus (mdG2) exhibits S100 and parvalbumin-positive fibers, apparently originating from all crypt cells plus some microvillous OSNs. Arguments for various olfactory labeled lines are discussed.

  16. Olfactory Dysfunction Predicts 5-Year Mortality in Older Adults

    PubMed Central

    Pinto, Jayant M.; Wroblewski, Kristen E.; Kern, David W.; Schumm, L. Philip; McClintock, Martha K.

    2014-01-01

    Prediction of mortality has focused on disease and frailty, although antecedent biomarkers may herald broad physiological decline. Olfaction, an ancestral chemical system, is a strong candidate biomarker because it is linked to diverse physiological processes. We sought to determine if olfactory dysfunction is a harbinger of 5-year mortality in the National Social Life, Health and Aging Project [NSHAP], a nationally representative sample of older U.S. adults. 3,005 community-dwelling adults aged 57–85 were studied in 2005–6 (Wave 1) and their mortality determined in 2010–11 (Wave 2). Olfactory dysfunction, determined objectively at Wave 1, was used to estimate the odds of 5-year, all cause mortality via logistic regression, controlling for demographics and health factors. Mortality for anosmic older adults was four times that of normosmic individuals while hyposmic individuals had intermediate mortality (p<0.001), a “dose-dependent” effect present across the age range. In a comprehensive model that included potential confounding factors, anosmic older adults had over three times the odds of death compared to normosmic individuals (OR, 3.37 [95%CI 2.04, 5.57]), higher than and independent of known leading causes of death, and did not result from the following mechanisms: nutrition, cognitive function, mental health, smoking and alcohol abuse or frailty. Olfactory function is thus one of the strongest predictors of 5-year mortality and may serve as a bellwether for slowed cellular regeneration or as a marker of cumulative toxic environmental exposures. This finding provides clues for pinpointing an underlying mechanism related to a fundamental component of the aging process. PMID:25271633

  17. Olfactory dysfunction predicts 5-year mortality in older adults.

    PubMed

    Pinto, Jayant M; Wroblewski, Kristen E; Kern, David W; Schumm, L Philip; McClintock, Martha K

    2014-01-01

    Prediction of mortality has focused on disease and frailty, although antecedent biomarkers may herald broad physiological decline. Olfaction, an ancestral chemical system, is a strong candidate biomarker because it is linked to diverse physiological processes. We sought to determine if olfactory dysfunction is a harbinger of 5-year mortality in the National Social Life, Health and Aging Project [NSHAP], a nationally representative sample of older U.S. adults. 3,005 community-dwelling adults aged 57-85 were studied in 2005-6 (Wave 1) and their mortality determined in 2010-11 (Wave 2). Olfactory dysfunction, determined objectively at Wave 1, was used to estimate the odds of 5-year, all cause mortality via logistic regression, controlling for demographics and health factors. Mortality for anosmic older adults was four times that of normosmic individuals while hyposmic individuals had intermediate mortality (p<0.001), a "dose-dependent" effect present across the age range. In a comprehensive model that included potential confounding factors, anosmic older adults had over three times the odds of death compared to normosmic individuals (OR, 3.37 [95%CI 2.04, 5.57]), higher than and independent of known leading causes of death, and did not result from the following mechanisms: nutrition, cognitive function, mental health, smoking and alcohol abuse or frailty. Olfactory function is thus one of the strongest predictors of 5-year mortality and may serve as a bellwether for slowed cellular regeneration or as a marker of cumulative toxic environmental exposures. This finding provides clues for pinpointing an underlying mechanism related to a fundamental component of the aging process.

  18. Testicular receptor 2, Nr2c1, is associated with stem cells in the developing olfactory epithelium and other cranial sensory and skeletal structures.

    PubMed

    Baker, Jennifer L; Wood, Bernard; Karpinski, Beverly A; LaMantia, Anthony-S; Maynard, Thomas M

    2016-01-01

    Comparative genomic analysis of the nuclear receptor family suggests that the testicular receptor 2, Nr2c1, undergoes positive selection in the human-chimpanzee clade based upon a significant increase in nonsynonymous compared to synonymous substitutions. Previous in situ analyses of Nr2c1 lacked the temporal range and spatial resolution necessary to characterize cellular expression of this gene from early to mid gestation, when many nuclear receptors are key regulators of tissue specific stem or progenitor cells. Thus, we asked whether Nr2c1 protein is associated with stem cell populations in the mid-gestation mouse embryo. Nr2c1 is robustly expressed in the developing olfactory epithelium. Its expression in the olfactory epithelium shifts from multiple progenitor classes at early stages to primarily transit amplifying cells later in olfactory epithelium development. In the early developing central nervous system, Nr2c1 is limited to the anterior telencephalon/olfactory bulb anlagen, coincident with Nestin-positive neuroepithelial stem cells. Nr2c1 is also seen in additional cranial sensory specializations including cells surrounding the mystacial vibrissae, the retinal pigment epithelium and Scarpa's ganglion. Nr2c1 was also detected in a subset of mesenchymal cells in developing teeth and cranial bones. The timing and distribution of embryonic expression suggests that Nr2c1 is primarily associated with the early genesis of mammalian cranial sensory neurons and craniofacial skeletal structures. Thus, Nr2c1 may be a candidate for mediating parallel adaptive changes in cranial neural sensory specializations such as the olfactory epithelium, retina and mystacial vibrissae and in non-neural craniofacial features including teeth.

  19. NanoCAGE analysis of the mouse olfactory epithelium identifies the expression of vomeronasal receptors and of proximal LINE elements

    PubMed Central

    Pascarella, Giovanni; Lazarevic, Dejan; Plessy, Charles; Bertin, Nicolas; Akalin, Altuna; Vlachouli, Christina; Simone, Roberto; Faulkner, Geoffrey J.; Zucchelli, Silvia; Kawai, Jun; Daub, Carsten O.; Hayashizaki, Yoshihide; Lenhard, Boris; Carninci, Piero; Gustincich, Stefano

    2013-01-01

    By coupling laser capture microdissection to nanoCAGE technology and next-generation sequencing we have identified the genome-wide collection of active promoters in the mouse Main Olfactory Epithelium (MOE). Transcription start sites (TSSs) for the large majority of Olfactory Receptors (ORs) have been previously mapped increasing our understanding of their promoter architecture. Here we show that in our nanoCAGE libraries of the mouse MOE we detect a large number of tags mapped in loci hosting Type-1 and Type-2 Vomeronasal Receptors genes (V1Rs and V2Rs). These loci also show a massive expression of Long Interspersed Nuclear Elements (LINEs). We have validated the expression of selected receptors detected by nanoCAGE with in situ hybridization, RT-PCR and qRT-PCR. This work extends the repertory of receptors capable of sensing chemical signals in the MOE, suggesting intriguing interplays between MOE and VNO for pheromone processing and positioning transcribed LINEs as candidate regulatory RNAs for VRs expression. PMID:24600346

  20. Transduction for Pheromones in the Main Olfactory Epithelium Is Mediated by the Ca2+-Activated Channel TRPM5

    PubMed Central

    López, Fabián; Delgado, Ricardo; López, Roberto; Bacigalupo, Juan

    2014-01-01

    Growing evidence suggests that the main olfactory epithelium contains a subset of olfactory sensory neurons (OSNs) responding to pheromones. One candidate subpopulation expresses the calcium activated cation channel TRPM5 (transient receptor potential channel M5). Using GFP driven by the TRPM5 promoter in mice, we show that this subpopulation responds to putative pheromones, urine, and major histocompatibility complex peptides, but not to regular odors or a pheromone detected by other species. In addition, this subpopulation of TRPM5-GFP+ OSNs uses novel transduction. In regular OSNs, odorants elicit activation of the cyclic nucleotide-gated (CNG) channel, leading to Ca2+ gating of Cl− channels; in TRPM5-GFP+ OSNs, the Ca2+-activated Cl− ANO2 (anoctamin 2) channel is not expressed, and pheromones elicit activation of the CNG channel leading to Ca2+ gating of TRPM5. In conclusion, we show that OSNs expressing TRPM5 respond to pheromones, but not to regular odors through the opening of CNG channels leading to Ca2+ gating of TRPM5. PMID:24573286

  1. Interactions with the young down-regulate adult olfactory neurogenesis and enhance the maturation of olfactory neuroblasts in sheep mothers

    PubMed Central

    Brus, Maïna; Meurisse, Maryse; Keller, Matthieu; Lévy, Frédéric

    2014-01-01

    New neurons are continuously added in the dentate gyrus (DG) and the olfactory bulb of mammalian brain. While numerous environmental factors controlling survival of newborn neurons have been extensively studied, regulation by social interactions is less documented. We addressed this question by investigating the influence of parturition and interactions with the young on neurogenesis in sheep mothers. Using Bromodeoxyuridine, a marker of cell division, in combination with markers of neuronal maturation, the percentage of neuroblasts and new mature neurons in the olfactory bulb and the DG was compared between groups of parturient ewes which could interact or not with their lamb, and virgins. In addition, a morphological analysis was performed by measuring the dendritic arbor of neuroblasts in both structures. We showed that the postpartum period was associated with a decrease in olfactory and hippocampal adult neurogenesis. In the olfactory bulb, the suppressive effect on neuroblasts was dependent on interactions with the young whereas in the DG the decrease in new mature neurons was associated with parturition. In addition, dendritic length and number of nodes of neuroblasts were significantly enhanced by interactions with the lamb in the olfactory bulb but not in the DG. Because interactions with the young involved learning of the olfactory signature of the lamb, we hypothesize that this learning is associated with a down-regulation in olfactory neurogenesis and an enhancement of olfactory neuroblast maturation. Our assumption is that fewer new neurons decrease cell competition in the olfactory bulb and enhance maturation of those new neurons selected to participate in the learning of the young odor. PMID:24600367

  2. Histopathological analysis of the olfactory epithelium of zebrafish (Danio rerio) exposed to sublethal doses of urea.

    PubMed

    Bettini, Simone; Lazzari, Maurizio; Ferrando, Sara; Gallus, Lorenzo; Franceschini, Valeria

    2016-01-01

    Chronic renal disease is known to alter olfactory function, but the specific changes induced in olfactory organs during this process remain unclear. Of the uraemic toxins generated during renal disease, high levels of urea are known to induce hyposmic conditions. In this study, the effects of environmental exposure to elevated concentrations of urea (7, 13.5 and 20 g L(-1)) on the sensory mucosa of zebrafish in acute toxicity and chronic toxicity tests were described. It was observed that lamellae maintained structural integrity and epithelial thickness was slightly reduced, but only following exposure to the highest concentrations of urea. Pan-neuronal labelling with anti-Hu revealed a negative correlation with levels of urea, leading to investigation of whether distinct neuronal subtypes were equally sensitive. Using densitometric analysis of immunolabelled tissues, numbers of Gα olf-, TRPC2- and TrkA-expressing cells were compared, representing ciliated, microvillous and crypt neurons, respectively. The three neuronal subpopulations responded differently to increasing levels of urea. In particular, crypt cells were more severely affected than the other cell types, and Gα olf-immunoreactivity was found to increase when fish were exposed to low doses of urea. It can be concluded that exposure to moderate levels of urea leads to sensory toxicity directly affecting olfactory organs, in accordance with the functional olfactometric measurements previously reported in the literature.

  3. Telomerase protects adult rodent olfactory ensheathing glia from early senescence.

    PubMed

    Llamusí, María-Beatriz; Rubio, Mari-Paz; Ramón-Cueto, Almudena

    2011-05-01

    Adult olfactory bulb ensheathing glia (OB-OEG) promote the repair of acute, subacute, and chronic spinal cord injuries and autologous transplantation is a feasible approach. There are interspecies differences between adult rodent and primate OB-OEG related to their longevity in culture. Whereas primate OB-OEG exhibit a relatively long life span, under the same culture conditions rodent OB-OEG divide just three to four times, are sensitive to oxidative stress and become senescent after the third week in vitro. Telomerase is a "physiological key regulator" of the life span of normal somatic cells and also has extratelomeric functions such as increased resistance to oxidative stress. To elucidate whether telomerase has a role in the senescence of rodent OB-OEG, we have introduced the catalytic subunit of telomerase mTERT into cultures of these cells by retroviral infection. Native and modified adult rat OB-OEG behaved as telomerase-competent cells as they divided while expressing mTERT but entered senescence once the gene switched off. After ectopic expression of mTERT, OB-OEG resumed division at a nonsenescent rate, expressed p75 and other OEG markers, and exhibited the morphology of nonsenescent OB-OEG. The nonsenescent period of mTERT-OEG lasted 9weeks and then ectopic mTERT switched off and cells entered senescence again. Our results suggest a role of telomerase in early senescence of adult rodent OB-OEG cultures and a protection from oxidative damage. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair.

  4. Topical Cathelicidin (LL-37) an Innate Immune Peptide Induces Acute Olfactory Epithelium Inflammation in a Mouse Model

    PubMed Central

    Alt, Jeremiah A.; Qin, Xuan; Pulsipher, Abigail; Orb, Quinn; Orlandi, Richard R.; Zhang, Jianxing; Schults, Austin; Jia, Wanjian; Presson, Angela P.; Prestwich, Glenn; Oottamasathien, Siam

    2017-01-01

    Background Cathelicidin (LL-37) is an endogenous innate immune peptide that is elevated in patients with chronic rhinosinusitis (CRS). The role of LL-37 in olfactory epithelium (OE) inflammation remains unknown. We hypothesized that 1) LL-37 topically delivered would elicit profound OE inflammation, and 2) LL-37 induced inflammation is associated with increased infiltration of neutrophils and mast cells. Methods To test our hypothesis we challenged C57BL/6 mice intranasally with increasing concentrations of LL-37. At 24 hours tissues were examined histologically and scored for inflammatory cell infiltrate, edema, and secretory hyperplasia. In separate experiments, fluorescently conjugated LL-37 was instilled and tissues were examined at 0.5 and 24 hours. To test our last hypothesis, we performed tissue myeloperoxidase (MPO) assays for neutrophil activity and immunohistochemistry for tryptase to determine the mean number of mast cells per mm2. Results LL-37 caused increased inflammatory cell infiltrate, edema, and secretory cell hyperplasia of the sinonasal mucosa with higher LL-37 concentrations yielding significantly more inflammatory changes (p < 0.01). Fluorescent LL-37 demonstrated global sinonasal epithelial binding and tissue distribution. Further, higher concentrations of LL-37 led to significantly greater MPO levels with dose-dependent increases in mast cell infiltration (p < 0.01). Conclusions LL-37 has dramatic inflammatory effects in the OE mucosa that is dose-dependent. The observed inflammatory changes in the olfactory mucosa were associated with the infiltration of both neutrophils and mast cells. Our biologic model represents a new model to further investigate the role of LL-37 in OE inflammation. PMID:26346056

  5. Neurogenesis in the vomeronasal epithelium of adult garter snakes: 3. Use of /sup 3/H-thymidine autoradiography to trace the genesis and migration of bipolar neurons

    SciTech Connect

    Wang, R.T.; Halpern, M.

    1988-10-01

    Use of 3H-thymidine autoradiography and unilateral vomeronasal (VN) axotomy has permitted us to demonstrate directly the existence of VN stem cells in the adult garter snake and to trace continuous bipolar neuron development and migration in the normal VN and deafferentated VN epithelium in the same animal. The vomeronasal epithelium and olfactory epithelium of adult garter snakes are both capable of incorporating 3H-thymidine. In the sensory epithelium of the vomeronasal organ, 3H-thymidine-labeled cells were initially restricted to the base of the undifferentiated cell layer in animals surviving 1 day following 3H-thymidine injection. With increasing survival time, labeled cells progressively migrated vertically within the receptor cell column toward the apex of the bipolar neuron layer. In both the normal and denervated VN epithelium, labeled cells were observed through the 56 days of postoperative survival. In the normal epithelium, labeled cells were always located within the matrix of the intact receptor cell columns. However, labeled cells of the denervated epithelium were always located at the apical front of the newly formed cell mass following depletion of the original neuronal cell population. In addition, at postoperative days 28 and 56, labeled cells of the denervated VN epithelium achieved neuronal differentiation and maturation by migrating much farther away from the base of the receptor cell column than the labeled cells on the normal, unoperated contralateral side. This study directly demonstrates that basal cells initially incorporating 3H-thymidine are indeed stem cells of the VN epithelium in adult garter snakes.

  6. Olfactory Detection Thresholds and Adaptation in Adults with Autism Spectrum Condition

    ERIC Educational Resources Information Center

    Tavassoli, T.; Baron-Cohen, S.

    2012-01-01

    Sensory issues have been widely reported in Autism Spectrum Conditions (ASC). Since olfaction is one of the least investigated senses in ASC, the current studies explore olfactory detection thresholds and adaptation to olfactory stimuli in adults with ASC. 80 participants took part, 38 (18 females, 20 males) with ASC and 42 control participants…

  7. Intranasal immunization with Naegleria fowleri lysates and Cry1Ac induces metaplasia in the olfactory epithelium and increases IgA secretion.

    PubMed

    Jarillo-Luna, A; Moreno-Fierros, L; Campos-Rodríguez, R; Rodríguez-Monroy, M A; Lara-Padilla, E; Rojas-Hernández, S

    2008-01-01

    According to previous reports, intranasal administration of the Cry1Ac protein alone or with amoebic lysates increases protection against Naegleria fowleri meningoencephalitis in mice, apparently by eliciting IgA responses in the nasal mucosa. In the current study, we performed an immunohistochemical analysis of IgA in the nasal mucosa of mice immunized intranasally with Cry1Ac, and amoebic lysates or a combination of both. The animals were sacrificed 24 h after the last immunization or after an intranasal lethal challenge with N. fowleri. Our results indicate that all of the intranasal immunizations provoked an increase in areas with metaplasia in the olfactory epithelium, allowing for secretion of IgA. As a result, IgA antibodies were found interacting with trophozoites in the nasal lumen, and there was a marked increase of IgA in the metaplasic epithelium. On the other hand in nonimmunized mice trophozoites were observed invading the nasal mucosa, which was not the case for immunized mice. Our results suggest that intranasal immunization provokes cellular changes in the olfactory epithelium, leading to greater protection against N. fowleri that is probably caused by an increased secretion of IgA. The increased IgA response induced in the nasal mucosa by immunization probably impedes both amoebic adhesion and subsequent invasion of the parasite to the nasal epithelium.

  8. Fate of marginal neuroblasts in the vomeronasal epithelium of adult mice.

    PubMed

    De La Rosa-Prieto, C; Saiz-Sanchez, D; Ubeda-Bañon, I; Argandoña-Palacios, L; Garcia-Muñozguren, S; Martinez-Marcos, A

    2009-12-10

    Chemical stimuli are sensed through the olfactory and vomeronasal epithelia, and the sensory cells of both systems undergo neuronal turnover during adulthood. In the vomeronasal epithelium, stem cells adjacent to the basal lamina divide and migrate to replace two classes of sensory neurons: apical neurons that express G(i2alpha)-linked V1R vomeronasal receptors and project to the anterior accessory olfactory bulb, and basal neurons that express G(oalpha)-linked V2R receptors and project to the posterior accessory olfactory bulb. Most of the dividing cells are present in the margins of the epithelium and only migrate locally. Previous studies have suggested that these marginal cells may participate in growth, sensory cell replacement or become apoptotic before maturation; however, the exact fate of these cells have remained unclear. In this work we investigated the fate of these marginal cells by analyzing markers of neurogenesis (bromodeoxyuridine incorporation), apoptosis (caspase-3), and neuronal maturation (olfactory marker protein and Neurotrace Nissl stain). Our data reveal a pool of dividing cells in the epithelial margins that predominantly give rise to mature neurons and only rarely undergo apoptosis. Newly generated cells are several times more numerous than apoptotic cells. These marginal neuroblasts could therefore constitute a net neural addition zone during adulthood.

  9. Nose-to-Brain Delivery: Investigation of the Transport of Nanoparticles with Different Surface Characteristics and Sizes in Excised Porcine Olfactory Epithelium.

    PubMed

    Mistry, Alpesh; Stolnik, Snjezana; Illum, Lisbeth

    2015-08-03

    The ability to deliver therapeutically relevant amounts of drugs directly from the nasal cavity to the central nervous system to treat neurological diseases is dependent on the availability of efficient drug delivery systems. Increased delivery and/or therapeutic effect has been shown for drugs encapsulated in nanoparticles; however, the factors governing the transport of the drugs and/or the nanoparticles from the nasal cavity to the brain are not clear. The present study evaluates the potential transport of nanoparticles across the olfactory epithelium in relation to nanoparticle characteristics. Model systems, 20, 100, and 200 nm fluorescent carboxylated polystyrene (PS) nanoparticles that were nonmodified or surface modified with polysorbate 80 (P80-PS) or chitosan (C-PS), were assessed for transport across excised porcine olfactory epithelium mounted in a vertical Franz diffusion cell. Assessment of the nanoparticle content in the donor chamber of the diffusion cell, accompanied by fluorescence microscopy of dismounted tissues, revealed a loss of nanoparticle content from the donor suspension and their association with the excised tissue, depending on the surface properties and particle size. Chitosan surface modification of PS nanoparticles resulted in the highest tissue association among the tested systems, with the associated nanoparticles primarily located in the mucus, whereas the polysorbate 80-modified nanoparticles showed some penetration into the epithelial cell layer. Assessment of the bioelectrical properties, metabolic activity, and histology of the excised olfactory epithelium showed that C-PS nanoparticles applied in pH 6.0 buffer produced a damaging effect on the epithelial cell layer in a size-dependent manner, with fine 20 nm sized nanoparticles causing substantial tissue damage relative to that with the 100 and 200 nm counterparts. Although histology showed that the olfactory tissue was affected by the application of citrate buffer that was

  10. Metamorphic remodeling of the olfactory organ of the African clawed frog, Xenopus laevis.

    PubMed

    Dittrich, Katarina; Kuttler, Josua; Hassenklöver, Thomas; Manzini, Ivan

    2016-04-01

    The amphibian olfactory system undergoes massive remodeling during metamorphosis. The transition from aquatic olfaction in larvae to semiaquatic or airborne olfaction in adults requires anatomical, cellular, and molecular modifications. These changes are particularly pronounced in Pipidae, whose adults have secondarily adapted to an aquatic life style. In the fully aquatic larvae of Xenopus laevis, the main olfactory epithelium specialized for sensing water-borne odorous substances lines the principal olfactory cavity (PC), whereas a separate olfactory epithelium lies in the vomeronasal organ (VNO). During metamorphosis, the epithelium of the PC is rearranged into the adult "air nose," whereas a new olfactory epithelium, the adult "water nose," forms in the emerging middle cavity (MC). Here we performed a stage-by-stage investigation of the anatomical changes of the Xenopus olfactory organ during metamorphosis. We quantified cell death in all olfactory epithelia and found massive cell death in the PC and the VNO, suggesting that the majority of larval sensory neurons is replaced during metamorphosis in both sensory epithelia. The moderate cell death in the MC shows that during the formation of this epithelium some cells are sorted out. Our results show that during MC formation some supporting cells, but not sensory neurons, are relocated from the PC to the MC and that they are eventually eliminated during metamorphosis. Together our findings illustrate the structural and cellular changes of the Xenopus olfactory organ during metamorphosis.

  11. Loss of olfactory function and nutritional status in vital older adults and geriatric patients.

    PubMed

    Toussaint, Nicole; de Roon, Margot; van Campen, Jos P C M; Kremer, Stefanie; Boesveldt, Sanne

    2015-03-01

    The aim of this cross-sectional study was to assess the association of olfactory function and nutritional status in vital older adults and geriatric patients. Three hundred forty-five vital (mean age 67.1 years) and 138 geriatric older adults (mean age 80.9 years) were included. Nutritional status was assessed using the mini nutritional assessment-short form. The Sniffin' Sticks was used to measure olfactory function. Eleven percentage of the vital older adults were at risk of malnutrition, whereas 60% of the geriatric participants were malnourished or at risk. Only 2% of the vital older adults were anosmic, compared with 46% of the geriatric participants. Linear regression demonstrated a significant association (P = 0.015) between olfactory function and nutritional status in the geriatric subjects. However, this association became insignificant after adjustment for confounders. Both crude and adjusted analysis in the vital older adults did not show a significant association. The results indicate that, in both groups of elderly, there is no direct relation between olfactory function and nutritional status. We suggest that a decline in olfactory function may still be considered as one of the risk-factors for malnutrition in geriatric patients-once co-occurring with other mental and/or physical problems that are more likely to occur in those patients experience.

  12. Reduction of the number of new cells reaching olfactory bulbs impairs olfactory perception in the adult opossum.

    PubMed

    Grabiec, Marta; Turlejski, Kris; Djavadian, Rouzanna

    2009-01-01

    In adult mammals cells generated in the subventricular zone (SVZ) migrate to olfactory bulbs (OB). Functional significance of this continuous neurogenesis is not clear. We injected opossums (Monodelphis domestica) for seven consecutive days with a 5HT(1A) agonist (8-OH-DPAT or buspirone) or its antagonist WAY100635. One hour after each of these injections bromodeoxyuridine (BrdU) a marker of dividing cells was also injected. Two months later, when newly generated neurons settled in the OB and matured the ability of these opossums to detect hidden food by olfactory cues was tested. Afterwards, numbers of BrdU-labeled cell nuclei in their OB were counted and a phenotype of labeled cells established. In all groups investigated the majority of new cells differentiated into neurons (55-76%) and a lower proportion into astroglia (6-12%). Numbers of BrdU-labeled cells differed depending on the applied treatment: both agonists of the 5HT(1A) receptor increased these numbers, while its antagonist decreased them. The increased number of new OB interneurons did not change the time required for finding all three food items and therefore did not improve the opossums' performance in this test of the olfactory perception. However, opossums that had the reduced number of new generated OB cells searched longer for each food item and in consequence took three times longer to find all three crickets, than did opossums from other groups. In conclusion, lower numbers of new neurons in the opossums OB correlated with their worse behavioral performance in a test based on olfactory perception.

  13. Elements of olfactory reception in adult Drosophila melanogaster.

    PubMed

    Martin, Fernando; Boto, Tamara; Gomez-Diaz, Carolina; Alcorta, Esther

    2013-09-01

    The olfactory system of Drosophila has become an attractive and simple model to investigate olfaction because it follows the same organizational principles of vertebrates, and the results can be directly applied to other insects with economic and sanitary relevance. Here, we review the structural elements of the Drosophila olfactory reception organs at the level of the cells and molecules involved. This article is intended to reflect the structural basis underlying the functional variability of the detection of an olfactory universe composed of thousands of odors. At the genetic level, we further detail the genes and transcription factors (TF) that determine the structural variability. The fly's olfactory receptor organs are the third antennal segments and the maxillary palps, which are covered with sensory hairs called sensilla. These sensilla house the odorant receptor neurons (ORNs) that express one or few odorant receptors in a stereotyped pattern regulated by combinations of TF. Also, perireceptor events, such as odor molecules transport to their receptors, are carried out by odorant binding proteins. In addition, the rapid odorant inactivation to preclude saturation of the system occurs by biotransformation and detoxification enzymes. These additional events take place in the lymph that surrounds the ORNs. We include some data on ionotropic and metabotropic olfactory transduction, although this issue is still under debate in Drosophila.

  14. Olfactory imprinting is correlated with changes in gene expression in the olfactory epithelia of the zebrafish.

    PubMed

    Harden, Maegan V; Newton, Lucy A; Lloyd, Russell C; Whitlock, Kathleen E

    2006-11-01

    Odors experienced as juveniles can have significant effects on the behavior of mature organisms. A dramatic example of this occurs in salmon, where the odors experienced by developing fish determine the river to which they return as adults. Further examples of olfactory memories are found in many animals including vertebrates and invertebrates. Yet, the cellular and molecular bases underlying the formation of olfactory memory are poorly understood. We have devised a series of experiments to determine whether zebrafish can form olfactory memories much like those observed in salmonids. Here we show for the first time that zebrafish form and retain olfactory memories of an artificial odorant, phenylethyl alcohol (PEA), experienced as juveniles. Furthermore, we demonstrate that exposure to PEA results in changes in gene expression within the olfactory sensory system. These changes are evident by in situ hybridization in the olfactory epithelium of the developing zebrafish. Strikingly, our analysis by in situ hybridization demonstrates that the transcription factor, otx2, is up regulated in the olfactory sensory epithelia in response to PEA. This increase is evident at 2-3 days postfertilization and is maintained in the adult animals. We propose that the changes in otx2 gene expression are manifest as an increase in the number of neuronal precursors in the cells olfactory epithelium of the odor-exposed fish. Thus, our results reveal a role for the environment in controlling gene expression in the developing peripheral nervous system.

  15. Olfactory function and the social lives of older adults: a matter of sex

    PubMed Central

    Boesveldt, Sanne; Yee, Jason R.; McClintock, Martha K.; Lundström, Johan N.

    2017-01-01

    Social factors play a critical role in a panoply of health processes, including, as recently demonstrated, olfaction. Here, we investigated sex-dependent differences in the relationship between social lives and ability to identify odors in a large sample of nationally representative older US adults (n = 3005, National Social Life and Aging Project (NSHAP)). Social life was measured by the number of friends and close relatives as well as frequency of socializing. We here confirm the association between social lives and olfactory function and extend the notion by showing specifically that olfactory identification ability is modulated by sex in older adults. The connection between olfactory performance and social lives could reflect social modulation of aging as has been reported for health in general. Future studies are necessary to elucidate the precise mechanisms underlying this association and sex difference. PMID:28327569

  16. Olfactory function and the social lives of older adults: a matter of sex.

    PubMed

    Boesveldt, Sanne; Yee, Jason R; McClintock, Martha K; Lundström, Johan N

    2017-03-22

    Social factors play a critical role in a panoply of health processes, including, as recently demonstrated, olfaction. Here, we investigated sex-dependent differences in the relationship between social lives and ability to identify odors in a large sample of nationally representative older US adults (n = 3005, National Social Life and Aging Project (NSHAP)). Social life was measured by the number of friends and close relatives as well as frequency of socializing. We here confirm the association between social lives and olfactory function and extend the notion by showing specifically that olfactory identification ability is modulated by sex in older adults. The connection between olfactory performance and social lives could reflect social modulation of aging as has been reported for health in general. Future studies are necessary to elucidate the precise mechanisms underlying this association and sex difference.

  17. Adult Olfactory Bulb Interneuron Phenotypes Identified by Targeting Embryonic and Postnatal Neural Progenitors

    PubMed Central

    Figueres-Oñate, Maria; López-Mascaraque, Laura

    2016-01-01

    Neurons are generated during embryonic development and in adulthood, although adult neurogenesis is restricted to two main brain regions, the hippocampus and olfactory bulb. The subventricular zone (SVZ) of the lateral ventricles generates neural stem/progenitor cells that continually provide the olfactory bulb (OB) with new granule or periglomerular neurons, cells that arrive from the SVZ via the rostral migratory stream. The continued neurogenesis and the adequate integration of these newly generated interneurons is essential to maintain homeostasis in the olfactory bulb, where the differentiation of these cells into specific neural cell types is strongly influenced by temporal cues. Therefore, identifying the critical features that control the generation of adult OB interneurons at either pre- or post-natal stages is important to understand the dynamic contribution of neural stem cells. Here, we used in utero and neonatal SVZ electroporation along with a transposase-mediated stable integration plasmid, in order to track interneurons and glial lineages in the OB. These plasmids are valuable tools to study the development of OB interneurons from embryonic and post-natal SVZ progenitors. Accordingly, we examined the location and identity of the adult progeny of embryonic and post-natally transfected progenitors by examining neurochemical markers in the adult OB. These data reveal the different cell types in the olfactory bulb that are generated in function of age and different electroporation conditions. PMID:27242400

  18. Olfactory and cortical projections to bulbar and hippocampal adult-born neurons

    PubMed Central

    De La Rosa-Prieto, Carlos; De Moya-Pinilla, Miguel; Saiz-Sanchez, Daniel; Ubeda-banon, Isabel; Arzate, Dulce M.; Flores-Cuadrado, Alicia; Liberia, Teresa; Crespo, Carlos; Martinez-Marcos, Alino

    2015-01-01

    New neurons are continually generated in the subependymal layer of the lateral ventricles and the subgranular zone of dentate gyrus during adulthood. In the subventricular zone, neuroblasts migrate a long distance to the olfactory bulb where they differentiate into granule or periglomerular interneurons. In the hippocampus, neuroblasts migrate a short distance from the subgranular zone to the granule cell layer of the dentate gyrus to become granule neurons. In addition to the short-distance inputs, bulbar interneurons receive long-distance centrifugal afferents from olfactory-recipient structures. Similarly, dentate granule cells receive differential inputs from the medial and lateral entorhinal cortices through the perforant pathway. Little is known concerning these new inputs on the adult-born cells. In this work, we have characterized afferent inputs to 21-day old newly-born neurons. Mice were intraperitoneally injected with bromodeoxyuridine. Two weeks later, rhodamine-labeled dextran-amine was injected into the anterior olfactory nucleus, olfactory tubercle, piriform cortex and lateral and medial entorhinal cortices. One week later, animals were perfused and immunofluorescences were carried out. The data show that projection neurons from the mentioned structures, establish putative synaptic contacts onto 21-day-old neurons in the olfactory bulb and dentate gyrus, in some cases even before they start to express specific subpopulation proteins. Long-distance afferents reach middle and outer one-third portions of the molecular layer of the dentate gyrus and granule and, interestingly, periglomerular layers of the olfactory bulb. In the olfactory bulb, these fibers appear to establish presumptive axo-somatic contacts onto newly-born granule and periglomerular cells. PMID:25698936

  19. Disruption of Adult Neurogenesis in the Olfactory Bulb Affects Social Interaction but not Maternal Behavior

    PubMed Central

    Feierstein, Claudia E.; Lazarini, Françoise; Wagner, Sebastien; Gabellec, Marie-Madeleine; de Chaumont, Fabrice; Olivo-Marin, Jean-Christophe; Boussin, François D.; Lledo, Pierre-Marie; Gheusi, Gilles

    2010-01-01

    Adult-born neurons arrive to the olfactory bulb (OB) and integrate into the existing circuit throughout life. Despite the prevalence of this phenomenon, its functional impact is still poorly understood. Recent studies point to the importance of newly generated neurons to olfactory learning and memory. Adult neurogenesis is regulated by a variety of factors, notably by instances related to reproductive behavior, such as exposure to mating partners, pregnancy and lactation, and exposure to offspring. To study the contribution of olfactory neurogenesis to maternal behavior and social recognition, here we selectively disrupted OB neurogenesis using focal irradiation of the subventricular zone in adult female mice. We show that reduction of olfactory neurogenesis results in an abnormal social interaction pattern with male, but not female, conspecifics; we suggest that this effect could result from the inability to detect or discriminate male odors and could therefore have implications for the recognition of potential mating partners. Disruption of OB neurogenesis, however, neither impaired maternal-related behaviors, nor did it affect the ability of mothers to discriminate their own progeny from others. PMID:21160552

  20. [Differentially expressed genes identified in the main olfactory epithelium of mice with deficiency of adenylate cyclase 3 by using suppression subtractive hybridization approach].

    PubMed

    Zhenlong, Cao; Jiangye, Hao; Yanfen, Zhou; Zhe, Zhang; Zhihua, Ni; Yuanxiang, Hu; Weili, Liu; Yongchao, Li; Daniel, R Storm; Runlin, Z Ma; Zhenshan, Wang

    2014-06-01

    Adenylate cyclase 3 (AC3) is one of the major players in the olfactory signaling within the main olfactory epithelium (MOE) of mice. However, we are not ascertained whether deficiency of AC3 will lead to the differential expression of related genes in the MOE. Forward and reverse subtractive libraries were constructed by suppression subtractive hybridization (SSH) approach, with MOEs from AC3(-/-) and AC3(+/+) mice. These two libraries were primarily screened by Dot blot, differential expressed clones were sequenced and analyzed by bioinformatics, and differential expressed genes were verified by qRT-PCR. A total of 386 differentially expressed clones were picked out after Dot blot. The DNA sequences of 80 clones randomly selected were determined, and 62 clones were identified by blasting in GenBank. We found that 24 up-regulated clones were corresponded to genes of kcnk3, mapk7, megf11, and 38 down-regulated clones were corresponded to tmem88b, c-mip, skp1a, mlycd, etc. Their functions were annotated with Gene Ontology (GO) and found to be mainly focused on molecular binding, cell cycle, processes of biology and cells. Five genes (kcnk3, c-mip, mlycd, tmem88b and trappc5) were verified by qRT-PCR with individuals of AC3(+/+) and AC3(-/-) mice. The data indicate that kcnk3 gene is up-regulated significantly, increasing 1.27 folds compared to control mice, whereas c-mip, mlycd, tmem88b and trappc5 are down-regulated significantly, decreasing 20%, 7%, 32% and 29% compared to the AC3(+/+)mice. The functions of these genes are closely related with K(+) channels, cell differentiation, metabolism of fats, membrane transportation, and so on. It is tempting to speculate that these genes might work together with AC3 to orchestrate the olfactory transduction signaling in the MOE.

  1. Adult Born Olfactory Bulb Dopaminergic Interneurons: Molecular Determinants and Experience-Dependent Plasticity

    PubMed Central

    Bonzano, Sara; Bovetti, Serena; Gendusa, Claudio; Peretto, Paolo; De Marchis, Silvia

    2016-01-01

    The olfactory bulb (OB) is a highly plastic brain region involved in the early processing of olfactory information. A remarkably feature of the OB circuits in rodents is the constitutive integration of new neurons that takes place during adulthood. Newborn cells in the adult OB are mostly inhibitory interneurons belonging to chemically, morphologically and functionally heterogeneous types. Although there is general agreement that adult neurogenesis in the OB plays a key role in sensory information processing and olfaction-related plasticity, the contribution of each interneuron subtype to such functions is far to be elucidated. Here, we focus on the dopaminergic (DA) interneurons: we highlight recent findings about their morphological features and then describe the molecular factors required for the specification/differentiation and maintenance of the DA phenotype in adult born neurons. We also discuss dynamic changes of the DA interneuron population related to age, environmental stimuli and lesions, and their possible functional implications. PMID:27199651

  2. Monoclonal antibody immunohistochemistry of degenerative and renewal patterns in rabbit olfactory receptor neurons following unilateral olfactory bulbectomy.

    PubMed

    Onoda, N

    1988-09-01

    Degeneration and regeneration of olfactory receptor neurons were studied in adult rabbits by immunohistochemical procedures following unilateral olfactory bulbectomy. Staining patterns of the olfactory receptors of the lesioned side were compared with those of the intact side in the nasal septum at various postoperative periods (12h-6 months) following lesion. Monoclonal antibodies, produced against the rabbit olfactory bulb, were used as histochemical markers. A slight decrease in the number of olfactory receptor neurons occurred at 24 h after lesion. One monoclonal antibody 112D5 stained all receptor neurons including degenerating neurons, but the other 114G12 showed a rapid decrease in immunostaining so that 114G12-positive cells disappeared within 7 days after lesion. 114G12-positive cells reappeared at 4 weeks following lesion. By 3 months, 114G12-positive cells were arranged in a plane at the apical region of the superficial compartment of the receptor cell layer, suggesting a recapitulation of development pattern of the receptor neurons. Thereafter, the number of 114G12-positive cells increased progressively and the staining pattern of the olfactory epithelium was like that of control animals by 6 months. Monoclonal antibody 114G12 is thus the first marker that is not specific to olfactory neurons and can be used to characterize certain embryonic traits during the degeneration and regeneration of the olfactory epithelium in the adult mammal.

  3. Morphological and behavioural changes occur following the X-ray irradiation of the adult mouse olfactory neuroepithelium

    PubMed Central

    2012-01-01

    Background The olfactory neuroepithelium lines the upper nasal cavity and is in direct contact with the external environment and the olfactory bulbs. The ability to self-renew throughout life and the reproducible recovery after injury, make it a model tissue to study mechanisms underlying neurogenesis. In this study, X-rays were used to disrupt proliferating olfactory stem cell populations and to assess their role in the cellular and morphological changes involved in olfactory neurogenic processes. Results We have analysed the histological and functional effects of a sub-lethal dose of X-rays on the adult mouse olfactory neuroepithelium at 2 hours, 24 hours, 1 week, 2 weeks and 5 weeks. We have shown an immediate cessation of proliferating olfactory stem cells as shown by BrdU, Ki67 and pH3 expression. At 24 hours there was an increase in the neural transcription factors Mash1 and Pax6 expression, and a disruption of the basal lamina and increase in glandular cell marker expression at 1 week post-irradiation. Coincident with these changes was an impairment of the olfactory function in vivo. Conclusions We have shown significant changes in basal cell proliferation as well as morphological changes in the olfactory neuroepithelium following X-ray irradiation. There is involvement of the basal lamina as well as a clear role for glandular and sustentacular cells. PMID:23113950

  4. The sox gene Dichaete is expressed in local interneurons and functions in development of the Drosophila adult olfactory circuit.

    PubMed

    Melnattur, Krishna V; Berdnik, Daniela; Rusan, Zeid; Ferreira, Christopher J; Nambu, John R

    2013-02-01

    In insects, the primary sites of integration for olfactory sensory input are the glomeruli in the antennal lobes. Here, axons of olfactory receptor neurons synapse with dendrites of the projection neurons that relay olfactory input to higher brain centers, such as the mushroom bodies and lateral horn. Interactions between olfactory receptor neurons and projection neurons are modulated by excitatory and inhibitory input from a group of local interneurons. While significant insight has been gleaned into the differentiation of olfactory receptor and projection neurons, much less is known about the development and function of the local interneurons. We have found that Dichaete, a conserved Sox HMG box gene, is strongly expressed in a cluster of LAAL cells located adjacent to each antennal lobe in the adult brain. Within these clusters, Dichaete protein expression is detected in both cholinergic and GABAergic local interneurons. In contrast, Dichaete expression is not detected in mature or developing projection neurons, or developing olfactory receptor neurons. Analysis of novel viable Dichaete mutant alleles revealed misrouting of specific projection neuron dendrites and axons, and alterations in glomeruli organization. These results suggest noncell autonomous functions of Dichaete in projection neuron differentiation as well as a potential role for Dichaete-expressing local interneurons in development of the adult olfactory circuitry.

  5. Effect of salinity changes on olfactory memory-related genes and hormones in adult chum salmon Oncorhynchus keta.

    PubMed

    Kim, Na Na; Choi, Young Jae; Lim, Sang-Gu; Jeong, Minhwan; Jin, Deuk-Hee; Choi, Cheol Young

    2015-09-01

    Studies of memory formation have recently concentrated on the possible role of N-methyl-d-aspartate receptors (NRs). We examined changes in the expression of three NRs (NR1, NR2B, and NR2C), olfactory receptor (OR), and adrenocorticotropic hormone (ACTH) in chum salmon Oncorhynchus keta using quantitative polymerase chain reaction (QPCR) during salinity change (seawater→50% seawater→freshwater). NRs were significantly detected in the diencephalon and telencephalon and OR was significantly detected in the olfactory epithelium. The expression of NRs, OR, and ACTH increased after the transition to freshwater. We also determined that treatment with MK-801, an antagonist of NRs, decreased NRs in telencephalon cells. In addition, a reduction in salinity was associated with increased levels of dopamine, ACTH, and cortisol (in vivo). Reductions in salinity evidently caused NRs and OR to increase the expression of cortisol and dopamine. We concluded that memory capacity and olfactory imprinting of salmon is related to the salinity of the environment during the migration to spawning sites. Furthermore, salinity affects the memory/imprinting and olfactory abilities, and cortisol and dopamine is also related with olfactory-related memories during migration.

  6. Olfactory processing in a changing brain.

    PubMed

    Lledo, Pierre-Marie; Gheusi, Gilles

    2003-09-15

    The perception of odorant molecules provides the essential information that allows animals to explore their surrounding. We describe here how the external world of scents may sculpt the activity of the first central relay of the olfactory system, i.e., the olfactory bulb. This structure is one of the few brain areas to continuously replace one of its neuronal populations: the local GABAergic interneurons. How the newly generated neurons integrate into a pre-existing neural network and how basic olfactory functions are maintained when a large percentage of neurons are subjected to continuous renewal, are important questions that have recently received new insights. Furthermore, we shall see how the adult neurogenesis is specifically subjected to experience-dependent modulation. In particular, we shall describe the sensitivity of the bulbar neurogenesis to the activity level of sensory inputs from the olfactory epithelium and, in turn, how this neurogenesis may adjust the neural network functioning to optimize odor information processing. Finally, we shall discuss the behavioral consequences of the bulbar neurogenesis and how it may be appropriate for the sense of smell. By maintaining a constitutive turnover of bulbar interneurons subjected to modulation by environmental cues, we propose that adult ongoing neurogenesis in the olfactory bulb is associated with improved olfactory memory. These recent findings not only provide new fuel for the molecular and cellular bases of sensory perception but should also shed light onto cellular bases of learning and memory.

  7. Local neurons play key roles in the mammalian olfactory bulb.

    PubMed

    Saghatelyan, Armen; Carleton, Alan; Lagier, Samuel; de Chevigny, Antoine; Lledo, Pierre-Marie

    2003-01-01

    Over the past few decades, research exploring how the brain perceives, discriminates, and recognizes odorant molecules has received a growing interest. Today, olfaction is no longer considered a matter of poetry. Chemical senses entered the biological era when an increasing number of scientists started to elucidate the early stages of the olfactory pathway. A combination of genetic, biochemical, cellular, electrophysiological and behavioral methods has provided a picture of how odor information is processed in the olfactory system as it moves from the periphery to higher areas of the brain. Our group is exploring the physiology of the main olfactory bulb, the first processing relay in the mammalian brain. From different electrophysiological approaches, we are attempting to understand the cellular rules that contribute to the synaptic transmission and plasticity at this central relay. How olfactory sensory inputs, originating from the olfactory epithelium located in the nasal cavity, are encoded in the main olfactory bulb remains a crucial question for understanding odor processing. More importantly, the persistence of a high level of neurogenesis continuously supplying the adult olfactory bulb with newborn local neurons provides an attractive model to investigate how basic olfactory functions are maintained when a large proportion of local neurons are continuously renewed. For this purpose, we summarize the current ideas concerning the molecular mechanisms and organizational strategies used by the olfactory system to encode and process information in the main olfactory bulb. We discuss the degree of sensitivity of the bulbar neuronal network activity to the persistence of this high level of neurogenesis that is modulated by sensory experience. Finally, it is worth mentioning that analyzing the molecular mechanisms and organizational strategies used by the olfactory system to transduce, encode, and process odorant information in the olfactory bulb should aid in

  8. A Comparison of the Olfactory Gene Repertoires of Adults and Larvae in the Noctuid Moth Spodoptera littoralis

    PubMed Central

    Poivet, Erwan; Gallot, Aurore; Montagné, Nicolas; Glaser, Nicolas; Legeai, Fabrice; Jacquin-Joly, Emmanuelle

    2013-01-01

    To better understand the olfactory mechanisms in a lepidopteran pest model species, the cotton leafworm Spodoptera littoralis, we have recently established a partial transcriptome from adult antennae. Here, we completed this transcriptome using next generation sequencing technologies, namely 454 and Illumina, on both adult antennae and larval tissues, including caterpillar antennae and maxillary palps. All sequences were assembled in 77,643 contigs. Their analysis greatly enriched the repertoire of chemosensory genes in this species, with a total of 57 candidate odorant-binding and chemosensory proteins, 47 olfactory receptors, 6 gustatory receptors and 17 ionotropic receptors. Using RT-PCR, we conducted the first exhaustive comparison of olfactory gene expression between larvae and adults in a lepidopteran species. All the 127 candidate olfactory genes were profiled for expression in male and female adult antennae and in caterpillar antennae and maxillary palps. We found that caterpillars expressed a smaller set of olfactory genes than adults, with a large overlap between these two developmental stages. Two binding proteins appeared to be larvae-specific and two others were adult-specific. Interestingly, comparison between caterpillar antennae and maxillary palps revealed numerous organ-specific transcripts, suggesting the complementary involvement of these two organs in larval chemosensory detection. Adult males and females shared the same set of olfactory transcripts, except two male-specific candidate pheromone receptors, two male-specific and two female-specific odorant-binding proteins. This study identified transcripts that may be important for sex-specific or developmental stage-specific chemosensory behaviors. PMID:23565215

  9. Olfactory experience modulates immature neuron development in postnatal and adult guinea pig piriform cortex.

    PubMed

    He, X; Zhang, X-M; Wu, J; Fu, J; Mou, L; Lu, D-H; Cai, Y; Luo, X-G; Pan, A; Yan, X-X

    2014-02-14

    Immature neurons expressing doublecortin (DCX+) are present around cortical layer II in various mammals including guinea pigs and humans, especially enriched in the paleocortex. However, little is known whether and how functional experience affects the development of this population of neurons. We attempted to explore a modulation by experience to layer II DCX+ cells in the primary olfactory cortex in postnatal and adult guinea pigs. Neonatal and 1-year-old guinea pigs were subjected to unilateral naris-occlusion, followed 1 and 2months later by morphometry of DCX+ cells in the piriform cortex. DCX+ somata and processes were reduced in the deprived relative to the non-deprived piriform cortex in both age groups at the two surviving time points. The number of DCX+ cells was decreased in the deprived side relative to internal control at 1 and 2months in the youths and at 2months in the adults post-occlusion. The mean somal area of DCX+ cells showed a trend of decrease in the deprived side relative to the internal control in the youths. In addition, DCX+ cells in the deprived side exhibited a lower frequency of colocalization with the neuron-specific nuclear antigen (NeuN) relative to counterparts. These results suggest that normal olfactory experience is required for the maintenance and development of DCX+ immature neurons in postnatal and adult guinea pig piriform cortex.

  10. Sensory deprivation increases phagocytosis of adult-born neurons by activated microglia in the olfactory bulb.

    PubMed

    Denizet, Marie; Cotter, Laurent; Lledo, Pierre-Marie; Lazarini, Françoise

    2017-02-01

    The olfactory bulb (OB) is a highly plastic structure that can change organizational networks depending on environmental inputs in adult mammals. Particularly, in rodents, adult neurogenesis underlies plastic changes in the OB circuitry by continuously adding new interneurons to the network. We addressed the question of whether microglia, the immune cells of the brain, were involved in pruning OB neurons. Using lentiviral labeling of neurons in neonatal or adult mice and confocal analysis, we showed that microglia engulfed parts of neonatal-born and adult-born neurons in the healthy OB. We demonstrated that OB deafferentation by Dichlobenil administration induced sensory deprivation. It also increased phagocytosis of adult-born, but not neonatal-born neurons, by activated microglia. Conversely, intranasal lipopolysaccharide administration induced activation of microglia but changed neither adult neurogenesis nor olfaction. Our data reveal that steady-state microglia eliminate adult-born neurons and their synapses in both healthy and sensory deprived OBs, thereby adapting neuronal connections to the sensory experience.

  11. Does the adult human ciliary body epithelium contain "true" retinal stem cells?

    PubMed

    Frøen, Rebecca; Johnsen, Erik O; Nicolaissen, Bjørn; Facskó, Andrea; Petrovski, Goran; Moe, Morten C

    2013-01-01

    Recent reports of retinal stem cells being present in several locations of the adult eye have sparked great hopes that they may be used to treat the millions of people worldwide who suffer from blindness as a result of retinal disease or injury. A population of proliferative cells derived from the ciliary body epithelium (CE) has been considered one of the prime stem cell candidates, and as such they have received much attention in recent years. However, the true nature of these cells in the adult human eye has still not been fully elucidated, and the stem cell claim has become increasingly controversial in light of new and conflicting reports. In this paper, we will try to answer the question of whether the available evidence is strong enough for the research community to conclude that the adult human CE indeed harbors stem cells.

  12. Regeneration of axotomized olfactory neurons in young and adult locusts quantified by fasciclin I immunofluorescence.

    PubMed

    Wasser, Hannah; Biller, Alexandra; Antonopoulos, Georgios; Meyer, Heiko; Bicker, Gerd; Stern, Michael

    2017-04-01

    The olfactory pathway of the locust Locusta migratoria is characterized by a multiglomerular innervation of the antennal lobe (AL) by olfactory receptor neurons (ORNs). After crushing the antenna and thereby severing ORN axons, changes in the AL were monitored. First, volume changes were measured at different times post-crush with scanning laser optical tomography in 5th instar nymphs. AL volume decreased significantly to a minimum volume at 4 days post-crush, followed by an increase. Second, anterograde labeling was used to visualize details in the AL and antennal nerve (AN) during de- and regeneration. Within 24 h post-crush (hpc) the ORN fragments distal to the lesion degenerated. After 48 hpc, regenerating fibers grew through the crush site. In the AL, labeled ORN projections disappeared completely and reappeared after a few days. A weak topographic match between ORN origin on the antenna and the position of innervated glomeruli that was present in untreated controls did not reappear after regeneration. Third, the cell surface marker fasciclin I that is expressed in ORNs was used for quantifying purposes. Immunofluorescence was measured in the AL during de- and regeneration in adults and 5th instar nymphs: after a rapid but transient, decrease, it reappeared. Both processes happen faster in 5th instar nymphs than in adults.

  13. Trop2 marks transient gastric fetal epithelium and adult regenerating cells after epithelial damage.

    PubMed

    Fernandez Vallone, Valeria; Leprovots, Morgane; Strollo, Sandra; Vasile, Gabriela; Lefort, Anne; Libert, Frederick; Vassart, Gilbert; Garcia, Marie-Isabelle

    2016-05-01

    Mouse fetal intestinal progenitors lining the epithelium prior to villogenesis grow as spheroids when cultured ex vivo and express the transmembrane glycoprotein Trop2 as a marker. Here, we report the characterization of Trop2-expressing cells from fetal pre-glandular stomach, growing as immortal undifferentiated spheroids, and their relationship with gastric development and regeneration. Trop2(+) cells generating gastric spheroids differed from adult glandular Lgr5(+) stem cells, but appeared highly related to fetal intestinal spheroids. Although they shared a common spheroid signature, intestinal and gastric fetal spheroid-generating cells expressed organ-specific transcription factors and were committed to intestinal and glandular gastric differentiation, respectively. Trop2 expression was transient during glandular stomach development, being lost at the onset of gland formation, whereas it persisted in the squamous forestomach. Undetectable under homeostasis, Trop2 was strongly re-expressed in glands after acute Lgr5(+) stem cell ablation or following indomethacin-induced injury. These highly proliferative reactive adult Trop2(+) cells exhibited a transcriptome displaying similarity with that of gastric embryonic Trop2(+) cells, suggesting that epithelium regeneration in adult stomach glands involves the partial re-expression of a fetal genetic program.

  14. The crypt cycle. Crypt and villus production in the adult intestinal epithelium.

    PubMed Central

    Totafurno, J; Bjerknes, M; Cheng, H

    1987-01-01

    We propose a model for the growth of individual crypts that is able to account for the observed changes in the number of cells in crypts under normal conditions, after irradiation, and after 30% resection. Parameter values for this model are estimated both for mouse and man, and detailed predictions of crypt growth rates are made. This model does not predict a steady-state crypt size; rather it suggests that crypts grow until they bifurcate. We therefore propose a crypt cycle (analogous to the cell cycle) and present evidence that most if not all crypts in the adult mouse are cycling asynchronously and independently. This evidence consists of four experiments that indicate that branching crypts are randomly distributed over the intestinal epithelium, that the plane of bifurcation of branching crypts is randomly oriented with respect to the villus base, and that the size distribution of crypts is consistent with an expanding crypt population. We also report for the first time evidence of villus production in the adult mouse intestinal epithelium. We conclude that the crypt and villus populations in the adult mouse are not in a steady state. Images FIGURE 4 PMID:3663832

  15. Olfactory organ of Octopus vulgaris: morphology, plasticity, turnover and sensory characterization

    PubMed Central

    Polese, Gianluca; Bertapelle, Carla

    2016-01-01

    ABSTRACT The cephalopod olfactory organ was described for the first time in 1844 by von Kölliker, who was attracted to the pair of small pits of ciliated cells on each side of the head, below the eyes close to the mantle edge, in both octopuses and squids. Several functional studies have been conducted on decapods but very little is known about octopods. The morphology of the octopus olfactory system has been studied, but only to a limited extent on post-hatching specimens, and the only paper on adult octopus gives a minimal description of the olfactory organ. Here, we describe the detailed morphology of young male and female Octopus vulgaris olfactory epithelium, and using a combination of classical morphology and 3D reconstruction techniques, we propose a new classification for O. vulgaris olfactory sensory neurons. Furthermore, using specific markers such as olfactory marker protein (OMP) and proliferating cell nuclear antigen (PCNA) we have been able to identify and differentially localize both mature olfactory sensory neurons and olfactory sensory neurons involved in epithelium turnover. Taken together, our data suggest that the O. vulgaris olfactory organ is extremely plastic, capable of changing its shape and also proliferating its cells in older specimens. PMID:27069253

  16. Olfactory bulbectomy, but not odor conditioned aversion, induces the differentiation of immature neurons in the adult rat piriform cortex.

    PubMed

    Gómez-Climent, M Á; Hernández-González, S; Shionoya, K; Belles, M; Alonso-Llosa, G; Datiche, F; Nacher, J

    2011-05-05

    The piriform cortex layer II of young-adult rats presents a population of prenatally generated cells, which express immature neuronal markers, such as the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) or doublecortin (DCX), and display structural characteristics of immature neurons. The number of PSA-NCAM/DCX expressing cells in this region decreases markedly as age progresses, suggesting that these cells differentiate or die. Since the piriform cortex receives a major input from the olfactory bulb and participates in olfactory information processing, it is possible that the immature neurons in layer II are affected by manipulations of the olfactory bulb or olfactory learning. It is not known whether these cells can be induced to differentiate and, if so, what would be their fate. In order to address these questions, we have performed unilateral olfactory bulbectomy (OBX) and an olfactory learning paradigm (taste-potentiated odor aversion, TPOA), in young-adult rats and have studied the expression of different mature and immature neuronal markers, as well as the presence of cell death. We have found that 14 h after OBX there was a dramatic decrease in the number of both PSA-NCAM and DCX expressing cells in piriform cortex layer II, whereas that of cells expressing NeuN, a mature neuronal marker, increased. By contrast, the number of cells expressing glutamate decarboxylase, isoform 67 (GAD67), a marker for interneurons, decreased slightly. Additionally, we have not found evidence of numbers of dying cells high enough to justify the disappearance of immature neurons. Analysis of animals subjected to TPOA revealed that this paradigm does not affect PSA-NCAM expressing cells. Our results strongly suggest that OBX can induce the maturation of immature neurons in the piriform cortex layer II and that these cells do not become interneurons. By contrast, these cells do not seem to play a crucial role in olfactory memory.

  17. Immunohistochemical localization and biochemical changes in catalase and superoxide dismutase during metamorphosis in the olfactory system of frog Microhyla ornata.

    PubMed

    Gaupale, Tekchand C; Londhe, Jayant; Ghaskadbi, Saroj; Subhedar, N K; Bhargava, Shobha

    2012-02-01

    Amphibian metamorphosis is characterized by rapid tissue remodeling and drastic changes in the body structure and function. Like other organs, olfactory system also undergoes a dramatic rearrangement as the animal experiences transition from aquatic to terrestrial habitat. Reactive oxygen species (ROS) are known to play an important role during anuran metamorphosis and role of antioxidant enzymes like catalase and superoxide dismutase (SOD) are believed to play a major role in these processes. Therefore, we hypothesize that antioxidant enzymes in the olfactory system may undergo changes that reflect metamorphic processes. Immunohistochemical study revealed the presence of catalase and SOD in the olfactory receptor neurons and also granular reaction in olfactory epithelium of medial diverticulum during metamorphosis. Catalase and SOD immunoreactivity were seen in the epithelium of lateral diverticulum, vomeronasal organ as metamorphosis proceeds and in the apical lining of olfactory epithelium of adult frog. Biochemical study showed that catalase activity gradually increases in the olfactory system from metamorphic stage 40-46 and adult, while SOD activity decreases from stage 40 to 46 and increases in adult. Thus, the localization and relative levels of catalase and SOD during metamorphosis in the olfactory system suggests that these enzymes may be involved in protection from oxidative damage.

  18. Early olfactory experience modifies neural activity in the antennal lobe of a social insect at the adult stage.

    PubMed

    Arenas, A; Giurfa, M; Farina, W M; Sandoz, J C

    2009-10-01

    In the antennal lobe (AL), the first olfactory centre of the insect brain, odorants are represented as spatiotemporal patterns of glomerular activity. Whether and how such patterns are modified in the long term after precocious olfactory experiences (i.e. in the first days of adulthood) remains unknown. To address this question, we used in vivo optical imaging of calcium activity in the antennal lobe of 17-day-old honeybees which either experienced an odorant associated with sucrose solution 5-8 days after emergence or were left untreated. In both cases, we imaged neural responses to the learned odor and to three novel odors varying in functional group and carbon-chain length. Two different odor concentrations were used. We also measured behavioral responses of 17-day-old honeybees, treated and untreated, to these stimuli. We show that precocious olfactory experience increased general odor-induced activity and the number of activated glomeruli in the adult AL, but also affected qualitative odor representations, which appeared shifted in the neural space of treated animals relative to control animals. Such effects were not limited to the experienced odor, but were generalized to other perceptually similar odors. A similar trend was found in behavioral experiments, in which increased responses to the learned odor extended to perceptually similar odors in treated bees. Our results show that early olfactory experiences have long-lasting effects, reflected in behavioral responses to odorants and concomitant neural activity in the adult olfactory system.

  19. Induction of ectopic taste buds by SHH reveals the competency and plasticity of adult lingual epithelium.

    PubMed

    Castillo, David; Seidel, Kerstin; Salcedo, Ernesto; Ahn, Christina; de Sauvage, Frederic J; Klein, Ophir D; Barlow, Linda A

    2014-08-01

    Taste buds are assemblies of elongated epithelial cells, which are innervated by gustatory nerves that transmit taste information to the brain stem. Taste cells are continuously renewed throughout life via proliferation of epithelial progenitors, but the molecular regulation of this process remains unknown. During embryogenesis, sonic hedgehog (SHH) negatively regulates taste bud patterning, such that inhibition of SHH causes the formation of more and larger taste bud primordia, including in regions of the tongue normally devoid of taste buds. Here, using a Cre-lox system to drive constitutive expression of SHH, we identify the effects of SHH on the lingual epithelium of adult mice. We show that misexpression of SHH transforms lingual epithelial cell fate, such that daughter cells of lingual epithelial progenitors form cell type-replete, onion-shaped taste buds, rather than non-taste, pseudostratified epithelium. These SHH-induced ectopic taste buds are found in regions of the adult tongue previously thought incapable of generating taste organs. The ectopic buds are composed of all taste cell types, including support cells and detectors of sweet, bitter, umami, salt and sour, and recapitulate the molecular differentiation process of endogenous taste buds. In contrast to the well-established nerve dependence of endogenous taste buds, however, ectopic taste buds form independently of both gustatory and somatosensory innervation. As innervation is required for SHH expression by endogenous taste buds, our data suggest that SHH can replace the need for innervation to drive the entire program of taste bud differentiation.

  20. Induction of ectopic taste buds by SHH reveals the competency and plasticity of adult lingual epithelium

    PubMed Central

    Castillo, David; Seidel, Kerstin; Salcedo, Ernesto; Ahn, Christina; de Sauvage, Frederic J.; Klein, Ophir D.; Barlow, Linda A.

    2014-01-01

    Taste buds are assemblies of elongated epithelial cells, which are innervated by gustatory nerves that transmit taste information to the brain stem. Taste cells are continuously renewed throughout life via proliferation of epithelial progenitors, but the molecular regulation of this process remains unknown. During embryogenesis, sonic hedgehog (SHH) negatively regulates taste bud patterning, such that inhibition of SHH causes the formation of more and larger taste bud primordia, including in regions of the tongue normally devoid of taste buds. Here, using a Cre-lox system to drive constitutive expression of SHH, we identify the effects of SHH on the lingual epithelium of adult mice. We show that misexpression of SHH transforms lingual epithelial cell fate, such that daughter cells of lingual epithelial progenitors form cell type-replete, onion-shaped taste buds, rather than non-taste, pseudostratified epithelium. These SHH-induced ectopic taste buds are found in regions of the adult tongue previously thought incapable of generating taste organs. The ectopic buds are composed of all taste cell types, including support cells and detectors of sweet, bitter, umami, salt and sour, and recapitulate the molecular differentiation process of endogenous taste buds. In contrast to the well-established nerve dependence of endogenous taste buds, however, ectopic taste buds form independently of both gustatory and somatosensory innervation. As innervation is required for SHH expression by endogenous taste buds, our data suggest that SHH can replace the need for innervation to drive the entire program of taste bud differentiation. PMID:24993944

  1. The Role of Adult-Born Neurons in the Constantly Changing Olfactory Bulb Network

    PubMed Central

    Malvaut, Sarah; Saghatelyan, Armen

    2016-01-01

    The adult mammalian brain is remarkably plastic and constantly undergoes structurofunctional modifications in response to environmental stimuli. In many regions plasticity is manifested by modifications in the efficacy of existing synaptic connections or synapse formation and elimination. In a few regions, however, plasticity is brought by the addition of new neurons that integrate into established neuronal networks. This type of neuronal plasticity is particularly prominent in the olfactory bulb (OB) where thousands of neuronal progenitors are produced on a daily basis in the subventricular zone (SVZ) and migrate along the rostral migratory stream (RMS) towards the OB. In the OB, these neuronal precursors differentiate into local interneurons, mature, and functionally integrate into the bulbar network by establishing output synapses with principal neurons. Despite continuous progress, it is still not well understood how normal functioning of the OB is preserved in the constantly remodelling bulbar network and what role adult-born neurons play in odor behaviour. In this review we will discuss different levels of morphofunctional plasticity effected by adult-born neurons and their functional role in the adult OB and also highlight the possibility that different subpopulations of adult-born cells may fulfill distinct functions in the OB neuronal network and odor behaviour. PMID:26839709

  2. The Role of Adult-Born Neurons in the Constantly Changing Olfactory Bulb Network.

    PubMed

    Malvaut, Sarah; Saghatelyan, Armen

    2016-01-01

    The adult mammalian brain is remarkably plastic and constantly undergoes structurofunctional modifications in response to environmental stimuli. In many regions plasticity is manifested by modifications in the efficacy of existing synaptic connections or synapse formation and elimination. In a few regions, however, plasticity is brought by the addition of new neurons that integrate into established neuronal networks. This type of neuronal plasticity is particularly prominent in the olfactory bulb (OB) where thousands of neuronal progenitors are produced on a daily basis in the subventricular zone (SVZ) and migrate along the rostral migratory stream (RMS) towards the OB. In the OB, these neuronal precursors differentiate into local interneurons, mature, and functionally integrate into the bulbar network by establishing output synapses with principal neurons. Despite continuous progress, it is still not well understood how normal functioning of the OB is preserved in the constantly remodelling bulbar network and what role adult-born neurons play in odor behaviour. In this review we will discuss different levels of morphofunctional plasticity effected by adult-born neurons and their functional role in the adult OB and also highlight the possibility that different subpopulations of adult-born cells may fulfill distinct functions in the OB neuronal network and odor behaviour.

  3. Odour enrichment increases adult-born dopaminergic neurons in the mouse olfactory bulb.

    PubMed

    Bonzano, Sara; Bovetti, Serena; Fasolo, Aldo; Peretto, Paolo; De Marchis, Silvia

    2014-11-01

    The olfactory bulb (OB) is the first brain region involved in the processing of olfactory information. In adult mice, the OB is highly plastic, undergoing cellular/molecular dynamic changes that are modulated by sensory experience. Odour deprivation induces down-regulation of tyrosine hydroxylase (TH) expression in OB dopaminergic interneurons located in the glomerular layer (GL), resulting in decreased dopamine in the OB. Although the effect of sensory deprivation is well established, little is known about the influence of odour enrichment on dopaminergic cells. Here we report that prolonged odour enrichment on C57BL/6J strain mice selectively increases TH-immunopositive cells in the GL by nearly 20%. Following odour enrichment on TH-green fluorescent protein (GFP) transgenic mice, in which GFP identified both mature TH-positive cells and putative immature dopaminergic cells expressing TH mRNA but not TH protein, we found a similar 20% increase in GFP-expressing cells, with no changes in the ratio between TH-positive and TH-negative cells. These data suggest that enriched conditions induce an expansion in the whole dopaminergic lineage. Accordingly, by using 5-bromo-2-deoxyuridine injections to label adult-generated cells in the GL of TH-GFP mice, we found an increase in the percentage of 5-bromo-2-deoxyuridine-positive dopaminergic cells in enriched compared with control conditions, whereas no differences were found for calretinin- and calbindin-positive subtypes. Strikingly, the fraction of newborn cells among the dopaminergic population doubled in enriched conditions. On the whole, our results demonstrate that odour enrichment drives increased integration of adult-generated dopaminergic cells that could be critical to adapt the OB circuits to the environmental incoming information.

  4. Role of the Retinoblastoma protein, Rb, during adult neurogenesis in the olfactory bulb

    PubMed Central

    Naser, Rayan; Vandenbosch, Renaud; Omais, Saad; Hayek, Dayana; Jaafar, Carine; Al Lafi, Sawsan; Saliba, Afaf; Baghdadi, Maarouf; Skaf, Larissa; Ghanem, Noël

    2016-01-01

    Adult neural stem cells (aNSCs) are relatively quiescent populations that give rise to distinct neuronal subtypes throughout life, yet, at a very low rate and restricted differentiation potential. Thus, identifying the molecular mechanisms that control their cellular expansion is critical for regeneration after brain injury. Loss of the Retinoblastoma protein, Rb, leads to several defects in cell cycle as well as neuronal differentiation and migration during brain development. Here, we investigated the role of Rb during adult neurogenesis in the olfactory bulb (OB) by inducing its temporal deletion in aNSCs and progenitors. Loss of Rb was associated with increased proliferation of adult progenitors in the subventricular zone (SVZ) and the rostral migratory stream (RMS) but did not alter self-renewal of aNSCs or neuroblasts subsequent migration and terminal differentiation. Hence, one month after their birth, Rb-null neuroblasts were able to differentiate into distinct subtypes of GABAergic OB interneurons but were gradually lost after 3 months. Similarly, Rb controlled aNSCs/progenitors proliferation in vitro without affecting their differentiation capacity. This enhanced SVZ/OB neurogenesis associated with loss of Rb was only transient and negatively affected by increased apoptosis indicating a critical requirement for Rb in the long-term survival of adult-born OB interneurons. PMID:26847607

  5. Adult frogs are sensitive to the predation risks of olfactory communication.

    PubMed

    Hamer, Rowena; Lemckert, Francis L; Banks, Peter B

    2011-06-23

    Olfaction is a common sensory mode of communication in much of the Vertebrata, although its use by adult frogs remains poorly studied. Being part of an open signalling system, odour cues can be exploited by 'eavesdropping' predators that hunt by smell, making association with odour a high-risk behaviour for prey. Here, we show that adult great barred frogs (Mixophes fasciolatus) are highly attracted to odour cues of conspecifics and those of sympatric striped marsh frogs (Limnodynastes peronii). This attraction decreased significantly with the addition of odours of a scent-hunting predator, the red-bellied black snake (Pseudechis porphyriacus), indicating that frogs perceived predation risks from associating with frog odours. Male frogs, however, maintained some attraction to unfamiliar conspecific scents even with predator odours present, suggesting that they perceived benefits of odour communication despite the risk. Our results indicate that adult frogs can identify species and individuals from their odours and assess the associated predation risk, revealing a complexity in olfactory communication previously unknown in adult anurans.

  6. Role of the Retinoblastoma protein, Rb, during adult neurogenesis in the olfactory bulb.

    PubMed

    Naser, Rayan; Vandenbosch, Renaud; Omais, Saad; Hayek, Dayana; Jaafar, Carine; Al Lafi, Sawsan; Saliba, Afaf; Baghdadi, Maarouf; Skaf, Larissa; Ghanem, Noël

    2016-02-05

    Adult neural stem cells (aNSCs) are relatively quiescent populations that give rise to distinct neuronal subtypes throughout life, yet, at a very low rate and restricted differentiation potential. Thus, identifying the molecular mechanisms that control their cellular expansion is critical for regeneration after brain injury. Loss of the Retinoblastoma protein, Rb, leads to several defects in cell cycle as well as neuronal differentiation and migration during brain development. Here, we investigated the role of Rb during adult neurogenesis in the olfactory bulb (OB) by inducing its temporal deletion in aNSCs and progenitors. Loss of Rb was associated with increased proliferation of adult progenitors in the subventricular zone (SVZ) and the rostral migratory stream (RMS) but did not alter self-renewal of aNSCs or neuroblasts subsequent migration and terminal differentiation. Hence, one month after their birth, Rb-null neuroblasts were able to differentiate into distinct subtypes of GABAergic OB interneurons but were gradually lost after 3 months. Similarly, Rb controlled aNSCs/progenitors proliferation in vitro without affecting their differentiation capacity. This enhanced SVZ/OB neurogenesis associated with loss of Rb was only transient and negatively affected by increased apoptosis indicating a critical requirement for Rb in the long-term survival of adult-born OB interneurons.

  7. Olfactory Perceptual Learning Requires Action of Noradrenaline in the Olfactory Bulb: Comparison with Olfactory Associative Learning

    ERIC Educational Resources Information Center

    Vinera, Jennifer; Kermen, Florence; Sacquet, Joëlle; Didier, Anne; Mandairon, Nathalie; Richard, Marion

    2015-01-01

    Noradrenaline contributes to olfactory-guided behaviors but its role in olfactory learning during adulthood is poorly documented. We investigated its implication in olfactory associative and perceptual learning using local infusion of mixed a1-ß adrenergic receptor antagonist (labetalol) in the adult mouse olfactory bulb. We reported that…

  8. Morphology of the epithelium of the lower rectum and the anal canal in the adult human.

    PubMed

    Tanaka, Eiichi; Noguchi, Tsuyoshi; Nagai, Kaoruko; Akashi, Yuichi; Kawahara, Katsunobu; Shimada, Tatsuo

    2012-06-01

    The anal canal is an important body part clinically. However, there is no agreement about the epithelium of the anal canal, the anal transitional zone (ATZ) epithelium in particular. The aim of this study is to clarify the structure of the epithelium of the human lower rectum and anal canal. Intact rectum and anus obtained from patients who underwent surgery for rectal carcinoma were examined by light and scanning electron microscopy (LM and SEM). By LM, three types of epithelium were observed in the anal canal: simple columnar epithelium, stratified squamous epithelium, and stratified columnar epithelium. The lower rectum was composed of simple columnar epithelium. SEM findings showed stratified squamous epithelium that consisted of squamous cells with microridges, changing to simple columnar epithelium consisting of columnar cells with short microvilli at the anorectal line. LM and SEM observations in a one-to-one ratio revealed that the area of stratified columnar epithelium based on LM corresponded to the anal crypt and sinus. In conclusion, the epithelium of the human anal canal was fundamentally composed of simple columnar epithelium and stratified squamous epithelium. We found no evidence of the ATZ.

  9. Detection of alpha-L fucose containing carbohydrates in mouse immature olfactory neurons.

    PubMed

    Ducray, A; Propper, A; Kastner, A

    1999-10-15

    The cellular location of alpha-L fucose was studied in mice olfactory epithelium (OE) using the Ulex europaeus agglutinin-I (UEA-I) and Tetragonolobus purpureas agglutinin (TPA). In adult mice, UEA-I and TPA revealed a layer of cells that mostly correspond to immature olfactory neurons. Moreover, autoradiographic studies after 3H-T incorporation showed that UEA-I cell labelling occurred during the week following the division of neural cell precursors. In newborn animals, active neurogenesis process is associated with a higher number of UEA-I labelled cells. Olfactory neurogenesis may thus involve a transient event of protein fucosylation, preceding axonal growth.

  10. Chronic inhibition of nitric oxide synthesis enhances both subventricular zone neurogenesis and olfactory learning in adult mice.

    PubMed

    Romero-Grimaldi, Carmen; Gheusi, Gilles; Lledo, Pierre-Marie; Estrada, Carmen

    2006-11-01

    The ability to generate new neurons during the course of adult life is preserved in the subventricular zone of the lateral ventricles and the dentate gyrus of the hippocampus in the mammalian brain. These two regions constitute specifically regulated neurogenic niches, and provide newborn neurons involved in olfactory and spatial learning, respectively. Nitric oxide (NO) is a negative regulator of neurogenesis in the subventricular zone, whereas its role in the dentate gyrus remains controversial. Using systemic administration of NO synthase (NOS) inhibitors to chronically inhibit NO production, we increased neural precursor proliferation in the subventricular zone as well as neurogenesis in the olfactory bulb, without modifying the number of mitotic cells or the granular cell layer thickness in the dentate gyrus. The same treatment specifically improved olfactory learning performance, whereas spatial learning and memory was unchanged, thus demonstrating that olfactory memory is closely associated with the level of ongoing neurogenesis in the subventricular zone-olfactory bulb. The anatomical specificity of the NOS inhibitor actions was not due to differences in the availability of NO, as demonstrated by immunohistochemical detection of neuronal NOS and S-nitrosylated proteins in both regions. Remarkably, the distinct NO sensitivity might result from a differential expression of epidermal growth factor receptor in precursor cells in both regions, as the proliferative effect of NOS inhibitors in the subventricular zone was restricted to the cells that expressed this receptor.

  11. The Rate of Age-Related Olfactory Decline Among the General Population of Older U.S. Adults

    PubMed Central

    Wroblewski, Kristen E.; Kern, David W.; Schumm, L. Philip; McClintock, Martha K.

    2015-01-01

    Background. Age-related olfactory loss (presbyosmia) is a prevalent sensory impairment with a large public health impact. In cross-sectional analyses, we found striking health disparities in olfactory function among older U.S. adults. Here, we report a 5-year follow-up to determine the magnitude of within-person olfactory decline. Methods. The National Social Life, Health, and Aging Project (NSHAP) interviewed a probability sample of home-dwelling older U.S. adults (57–85 years) in 2005–2006 (Wave 1) and reinterviewed them in 2010–2011 (Wave 2), assessing demographics, social life, and health, including olfaction. Odor identification was measured with a 5-item version of the Sniffin’ Sticks (0–5 correct). Fourteen hundred and thirty-six respondents provided olfaction data in both waves. Multivariate linear and logistic regression were used to model the association between change in olfactory performance and demographic, health, and psychosocial factors. Results. Odor identification declined most rapidly among older individuals (0.25 additional errors per 5 years for each decade of age, p < .001) and in men (0.17 additional errors per 5 years compared to women, p = .005). Among those with perfect scores in Wave 1, African Americans declined more rapidly than Whites (p = .04). Neither socioeconomic status, health conditions, cognition, mental health, alcohol use nor smoking was associated with change in olfaction (p > .05, all). Conclusions. The rate of olfactory decline increases with age and is greater among men than women despite adjusting for differences in psychosocial and health conditions, indicating physiologic factors as drivers. African Americans are more likely to experience initial olfactory decline, consistent with an earlier onset of aging among this subgroup. PMID:26253908

  12. Principal cell activity induces spine relocation of adult-born interneurons in the olfactory bulb

    PubMed Central

    Breton-Provencher, Vincent; Bakhshetyan, Karen; Hardy, Delphine; Bammann, Rodrigo Roberto; Cavarretta, Francesco; Snapyan, Marina; Côté, Daniel; Migliore, Michele; Saghatelyan, Armen

    2016-01-01

    Adult-born neurons adjust olfactory bulb (OB) network functioning in response to changing environmental conditions by the formation, retraction and/or stabilization of new synaptic contacts. While some changes in the odour environment are rapid, the synaptogenesis of adult-born neurons occurs over a longer time scale. It remains unknown how the bulbar network functions when rapid and persistent changes in environmental conditions occur but when new synapses have not been formed. Here we reveal a new form of structural remodelling where mature spines of adult-born but not early-born neurons relocate in an activity-dependent manner. Principal cell activity induces directional growth of spine head filopodia (SHF) followed by spine relocation. Principal cell-derived glutamate and BDNF regulate SHF motility and directional spine relocation, respectively; and spines with SHF are selectively preserved following sensory deprivation. Our three-dimensional model suggests that spine relocation allows fast reorganization of OB network with functional consequences for odour information processing. PMID:27578235

  13. Olfactory Dysfunction in Older Adults is Associated with Feelings of Depression and Loneliness.

    PubMed

    Sivam, Anita; Wroblewski, Kristen E; Alkorta-Aranburu, Gorka; Barnes, Lisa L; Wilson, Robert S; Bennett, David A; Pinto, Jayant M

    2016-05-01

    Olfactory dysfunction is a common complaint among physician visits. Olfactory loss affects quality of life and impairs function and activities of daily living. The purpose of our study was to assess the degree of odor identification associated with mental health. Olfactory function was measured using the brief smell identification test. Depressive symptoms were measured by the Center for Epidemiologic Studies Depression scale. Loneliness was assessed by the de Jong-Gierveld Loneliness Scale. Cognition was measured by a battery of 19 cognitive tests. The frequency of olfactory dysfunction in our study was ~40%. Older subjects had worse olfactory performance, as previously found. More loneliness was associated with worse odor identification. Similarly, symptoms of depression were associated with worse olfaction (among men). Although better global cognitive function was strongly associated with better odor identification, after controlling for multiple factors, the associations with depression and loneliness were unchanged. Clinicians should assess these mental health conditions when treating older patients who present with olfactory deficits.

  14. Olfactory discrimination predicts cognitive decline among community-dwelling older adults.

    PubMed

    Sohrabi, H R; Bates, K A; Weinborn, M G; Johnston, A N B; Bahramian, A; Taddei, K; Laws, S M; Rodrigues, M; Morici, M; Howard, M; Martins, G; Mackay-Sim, A; Gandy, S E; Martins, R N

    2012-05-22

    The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46-86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions using the Sniffin' Sticks battery indicated that, contrary to previous findings, olfactory discrimination, but not olfactory identification, significantly predicted subsequent cognitive decline (odds ratio = 0.869; P<0.05; 95% confidence interval = 0.764-0.988). The current study findings confirm previously reported associations between olfactory and cognitive functions, and indicate that impairment in olfactory discrimination can predict future cognitive decline. These findings further our current understanding of the association between cognition and olfaction, and support olfactory assessment in screening those at higher risk of dementia.

  15. A lifetime of neurogenesis in the olfactory system

    PubMed Central

    Brann, Jessica H.; Firestein, Stuart J.

    2014-01-01

    Neurogenesis continues well beyond embryonic and early postnatal ages in three areas of the nervous system. The subgranular zone supplies new neurons to the dentate gyrus of the hippocampus. The subventricular zone supplies new interneurons to the olfactory bulb, and the olfactory neuroepithelia generate new excitatory sensory neurons that send their axons to the olfactory bulb. The latter two areas are of particular interest as they contribute new neurons to both ends of a first-level circuit governing olfactory perception. The vomeronasal organ and the main olfactory epithelium comprise the primary peripheral olfactory epithelia. These anatomically distinct areas share common features, as each exhibits extensive neurogenesis well beyond the juvenile phase of development. Here we will discuss the effect of age on the structural and functional significance of neurogenesis in the vomeronasal and olfactory epithelia, from juvenile to advanced adult ages, in several common model systems. We will next discuss how age affects the regenerative capacity of these neural stem cells in response to injury. Finally, we will consider the integration of newborn neurons into an existing circuit as it is modified by the age of the animal. PMID:25018692

  16. Action of the noradrenergic system on adult-born cells is required for olfactory learning in mice.

    PubMed

    Moreno, Melissa M; Bath, Kevin; Kuczewski, Nicola; Sacquet, Joëlle; Didier, Anne; Mandairon, Nathalie

    2012-03-14

    We have previously shown that an experience-driven improvement in olfactory discrimination (perceptual learning) requires the addition of newborn neurons in the olfactory bulb (OB). Despite this advance, the mechanisms which govern the selective survival of newborn OB neurons following learning remain largely unknown. We propose that activity of the noradrenergic system is a critical mediator providing a top-down signal to control the selective survival of newly born cells and support perceptual learning. In adult mice, we used pharmacological means to manipulate the noradrenergic system and neurogenesis and to assess their individual and additive effects on behavioral performance on a perceptual learning task. We then looked at the effects of these manipulations on regional survival of adult-born cells in the OB. Finally, using confocal imaging and electrophysiology, we investigated potential mechanisms by which noradrenaline could directly influence the survival of adult-born cells. Consistent with our hypotheses, direct manipulation of noradrenergic transmission significantly effect on adult-born cell survival and perceptual learning. Specifically, learning required both the presence of adult-born cell and noradrenaline. Finally, we provide a mechanistic link between these effects by showing that adult-born neurons receive noradrenergic projections and are responsive to noradrenaline. Based upon these data we argue that noradrenergic transmission is a key mechanism selecting adult-born neurons during learning and demonstrate that top-down neuromodulation acts on adult-born neuron survival to modulate learning performance.

  17. Neural stem cells in the adult ciliary epithelium express GFAP and are regulated by Wnt signaling

    SciTech Connect

    Das, Ani V.; Zhao Xing; James, Jackson; Kim, Min; Cowan, Kenneth H.; Ahmad, Iqbal . E-mail: iahmad@unmc.edu

    2006-01-13

    The identification of neural stem cells with retinal potential in the ciliary epithelium (CE) of the adult mammals is of considerable interest because of their potential for replacing or rescuing degenerating retinal neurons in disease or injury. The evaluation of such a potential requires characterization of these cells with regard to their phenotypic properties, potential, and regulatory mechanisms. Here, we demonstrate that rat CE stem cells/progenitors in neurosphere culture display astrocytic nature in terms of expressing glial intermediate neurofilament protein, GFAP. The GFAP-expressing CE stem cells/progenitors form neurospheres in proliferating conditions and generate neurons when shifted to differentiating conditions. These cells express components of the canonical Wnt pathway and its activation promotes their proliferation. Furthermore, we demonstrate that the activation of the canonical Wnt pathway influences neuronal differentiation of CE stem cells/progenitors in a context dependent manner. Our observations suggest that CE stem cells/progenitors share phenotypic properties and regulatory mechanism(s) with neural stem cells elsewhere in the adult CNS.

  18. Influence of Dietary Experience on the Induction of Preference of Adult Moths and Larvae for a New Olfactory Cue.

    PubMed

    Petit, Christophe; Le Ru, Bruno; Dupas, Stéphane; Frérot, Brigitte; Ahuya, Peter; Kaiser-Arnauld, Laure; Harry, Myriam; Calatayud, Paul-André

    2015-01-01

    In Lepidoptera, host plant selection is first conditioned by oviposition site preference of adult females followed by feeding site preference of larvae. Dietary experience to plant volatile cues can induce larval and adult host plant preference. We investigated how the parent's and self-experience induce host preference in adult females and larvae of three lepidopteran stem borer species with different host plant ranges, namely the polyphagous Sesamia nonagrioides, the oligophagous Busseola fusca and the monophagous Busseola nairobica, and whether this induction can be linked to a neurophysiological phenotypic plasticity. The three species were conditioned to artificial diet enriched with vanillin from the neonate larvae to the adult stage during two generations. Thereafter, two-choice tests on both larvae and adults using a Y-tube olfactometer and electrophysiological (electroantennography [EAG] recordings) experiments on adults were carried out. In the polyphagous species, the induction of preference for a new olfactory cue (vanillin) by females and 3rd instar larvae was determined by parents' and self-experiences, without any modification of the sensitivity of the females antennae. No preference induction was found in the oligophagous and monophagous species. Our results suggest that lepidopteran stem borers may acquire preferences for new olfactory cues from the larval to the adult stage as described by Hopkins' host selection principle (HHSP), neo-Hopkins' principle, and the concept of 'chemical legacy.'

  19. Reduced olfactory bulb volume in adults with a history of childhood maltreatment.

    PubMed

    Croy, Ilona; Negoias, Simona; Symmank, Anja; Schellong, Julia; Joraschky, Peter; Hummel, Thomas

    2013-10-01

    The human olfactory bulb (OB) is the first relay station of the olfactory pathway and may have the potential for postnatal neurogenesis in early childhood. In animals, chronic stress affects the OB and olfactory functioning. For humans, it has been shown that major depressive disorder is accompanied by reduced OB volume and reduced olfactory function. However, it is not clear if major stress in childhood development also affects olfactory functioning and OB volume in humans. OB volume was measured and olfactory function was tested in 17 depressive patients with and 10 without a history of severe childhood maltreatment (CM). CM patients exhibited a significantly reduced olfactory threshold and identification ability. The OB volume of the CM patients was significantly reduced to 80% of the non-CM patients. In conclusion, postnatal neurogenesis might be by reduced in CM, which may affect olfactory function of the brain in later life. Alternatively, a reduced OB volume may enhance psychological vulnerability in the presence of adverse childhood conditions although other areas not analyzed in this study may also be involved.

  20. A neonicotinoid impairs olfactory learning in Asian honey bees (Apis cerana) exposed as larvae or as adults.

    PubMed

    Tan, Ken; Chen, Weiwen; Dong, Shihao; Liu, Xiwen; Wang, Yuchong; Nieh, James C

    2015-06-18

    Xenobiotics such as the neonicotinoid pesticide, imidacloprid, are used globally, but their effects on native bee species are poorly understood. We studied the effects of sublethal doses of imidacloprid on olfactory learning in the native honey bee species, Apis cerana, an important pollinator of agricultural and native plants throughout Asia. We provide the first evidence that imidacloprid can impair learning in A. cerana workers exposed as adults or as larvae. Adults that ingested a single imidacloprid dose as low as 0.1 ng/bee had significantly reduced olfactory learning acquisition, which was 1.6-fold higher in control bees. Longer-term learning (1-17 h after the last learning trial) was also impaired. Bees exposed as larvae to a total dose of 0.24 ng/bee did not have reduced survival to adulthood. However, these larval-treated bees had significantly impaired olfactory learning when tested as adults: control bees exhibited up to 4.8-fold better short-term learning acquisition, though longer-term learning was not affected. Thus, sublethal cognitive deficits elicited by neonicotinoids on a broad range of native bee species deserve further study.

  1. Fragile X Mental Retardation Protein Regulates New Neuron Differentiation in the Adult Olfactory Bulb

    PubMed Central

    Scotto-Lomassese, Sophie; Nissant, Antoine; Mota, Tatiana; Néant-Féry, Marie; Oostra, Ben A.; Greer, Charles A.; Lledo, Pierre-Marie; Trembleau, Alain; Caillé, Isabelle

    2013-01-01

    The fragile X mental retardation protein (FMRP) is an RNA-binding protein essential for multiple aspects of neuronal mRNA metabolism. Its absence leads to the fragile X syndrome, the most prevalent genetic form of mental retardation. The anatomical landmark of the disease, also present in the Fmr1 knock-out (KO) mice, is the hyperabundance of immature-looking lengthened dendritic spines. We used the well known continuous production of adult-born granule cells (GCs) in the mouse olfactory bulb (OB) to analyze the consequences of Fmrp loss on the differentiation of GCs. Morphological analysis of GCs in the Fmr1 KO mice showed an increase in spine density without a change in spine length. We developed an RNA interference strategy to cell-autonomously mutate Fmr1 in a wild-type OB network. Mutated GCs displayed an increase in spine density and spine length. Detailed analysis of the spines through immunohistochemistry, electron microscopy, and electrophysiology surprisingly showed that, despite these abnormalities, spines receive normal glutamatergic synapses, and thus that mutated adult-born neurons are synaptically integrated into the OB circuitry. Time-course analysis of the spine defects showed that Fmrp cell-autonomously downregulates the level and rate of spine production and limits their overgrowth. Finally, we report that Fmrp does not regulate dendritogenesis in standard conditions but is necessary for activity-dependent dendritic remodeling. Overall, our study of Fmrp in the context of adult neurogenesis has enabled us to carry out a precise dissection of the role of Fmrp in neuronal differentiation and underscores its pleiotropic involvement in both spinogenesis and dendritogenesis. PMID:21307257

  2. Fragile X mental retardation protein regulates new neuron differentiation in the adult olfactory bulb.

    PubMed

    Scotto-Lomassese, Sophie; Nissant, Antoine; Mota, Tatiana; Néant-Féry, Marie; Oostra, Ben A; Greer, Charles A; Lledo, Pierre-Marie; Trembleau, Alain; Caillé, Isabelle

    2011-02-09

    The fragile X mental retardation protein (FMRP) is an RNA-binding protein essential for multiple aspects of neuronal mRNA metabolism. Its absence leads to the fragile X syndrome, the most prevalent genetic form of mental retardation. The anatomical landmark of the disease, also present in the Fmr1 knock-out (KO) mice, is the hyperabundance of immature-looking lengthened dendritic spines. We used the well known continuous production of adult-born granule cells (GCs) in the mouse olfactory bulb (OB) to analyze the consequences of Fmrp loss on the differentiation of GCs. Morphological analysis of GCs in the Fmr1 KO mice showed an increase in spine density without a change in spine length. We developed an RNA interference strategy to cell-autonomously mutate Fmr1 in a wild-type OB network. Mutated GCs displayed an increase in spine density and spine length. Detailed analysis of the spines through immunohistochemistry, electron microscopy, and electrophysiology surprisingly showed that, despite these abnormalities, spines receive normal glutamatergic synapses, and thus that mutated adult-born neurons are synaptically integrated into the OB circuitry. Time-course analysis of the spine defects showed that Fmrp cell-autonomously downregulates the level and rate of spine production and limits their overgrowth. Finally, we report that Fmrp does not regulate dendritogenesis in standard conditions but is necessary for activity-dependent dendritic remodeling. Overall, our study of Fmrp in the context of adult neurogenesis has enabled us to carry out a precise dissection of the role of Fmrp in neuronal differentiation and underscores its pleiotropic involvement in both spinogenesis and dendritogenesis.

  3. Adult retinal pigment epithelium cells express neural progenitor properties and the neuronal precursor protein doublecortin.

    PubMed

    Engelhardt, Maren; Bogdahn, Ulrich; Aigner, Ludwig

    2005-04-08

    The adult mammalian retina is devoid of any detectable neurogenesis. However, different cell types have been suggested to potentially act as neural progenitors in the adult mammalian retina in vitro, such as ciliary body (CB), Muller glia, and retinal pigment epithelium (RPE) cells. In rodents and humans, strong evidence for neural stem or progenitor properties exists only for CB-derived cells, but not for other retinal cell types. Here, we provide a comparative analysis of adult rat CB- and RPE-derived cells suggesting that the two cell types share certain neural progenitor properties in vitro. CB and RPE cells expressed neural progenitor markers such as Nestin, Flk-1, Hes1, and Musashi. They proliferated under adherent and neurosphere conditions and showed limited self-renewal. Moreover, they differentiated into neuronal and glial cells based on the expression of differentiation markers such as the young neuronal marker beta-III tubulin and the glial and progenitor markers GFAP and NG2. Expression of beta-III tubulin was found in cells with neuronal and non-neuronal morphology. A subpopulation of RPE- and CB-derived progenitor cells expressed the neurogenesis-specific protein doublecortin (DCX). Interestingly, DCX expression defined a beta-III tubulin-positive CB and RPE fraction with a distinct neuronal morphology. In summary, the data suggest that RPE cells share with CB cells the potential to de-differentiate into a cell type with neural progenitor-like identity. In addition, DCX expression might define the neuronal-differentiating RPE- and CB-derived progenitor population.

  4. Odorant-dependent generation of nitric oxide in Mammalian olfactory sensory neurons.

    PubMed

    Brunert, Daniela; Kurtenbach, Stefan; Isik, Sonnur; Benecke, Heike; Gisselmann, Günter; Schuhmann, Wolfgang; Hatt, Hanns; Wetzel, Christian H

    2009-01-01

    The gaseous signalling molecule nitric oxide (NO) is involved in various physiological processes including regulation of blood pressure, immunocytotoxicity and neurotransmission. In the mammalian olfactory bulb (OB), NO plays a role in the formation of olfactory memory evoked by pheromones as well as conventional odorants. While NO generated by the neuronal isoform of NO synthase (nNOS) regulates neurogenesis in the olfactory epithelium, NO has not been implicated in olfactory signal transduction. We now show the expression and function of the endothelial isoform of NO synthase (eNOS) in mature olfactory sensory neurons (OSNs) of adult mice. Using NO-sensitive micro electrodes, we show that stimulation liberates NO from isolated wild-type OSNs, but not from OSNs of eNOS deficient mice. Integrated electrophysiological recordings (electro-olfactograms or EOGs) from the olfactory epithelium of these mice show that NO plays a significant role in modulating adaptation. Evidence for the presence of eNOS in mature mammalian OSNs and its involvement in odorant adaptation implicates NO as an important new element involved in olfactory signal transduction. As a diffusible messenger, NO could also have additional functions related to cross adaptation, regeneration, and maintenance of MOE homeostasis.

  5. Odorant-Dependent Generation of Nitric Oxide in Mammalian Olfactory Sensory Neurons

    PubMed Central

    Brunert, Daniela; Kurtenbach, Stefan; Isik, Sonnur; Benecke, Heike; Gisselmann, Günter; Schuhmann, Wolfgang; Hatt, Hanns; Wetzel, Christian H.

    2009-01-01

    The gaseous signalling molecule nitric oxide (NO) is involved in various physiological processes including regulation of blood pressure, immunocytotoxicity and neurotransmission. In the mammalian olfactory bulb (OB), NO plays a role in the formation of olfactory memory evoked by pheromones as well as conventional odorants. While NO generated by the neuronal isoform of NO synthase (nNOS) regulates neurogenesis in the olfactory epithelium, NO has not been implicated in olfactory signal transduction. We now show the expression and function of the endothelial isoform of NO synthase (eNOS) in mature olfactory sensory neurons (OSNs) of adult mice. Using NO-sensitive micro electrodes, we show that stimulation liberates NO from isolated wild-type OSNs, but not from OSNs of eNOS deficient mice. Integrated electrophysiological recordings (electro-olfactograms or EOGs) from the olfactory epithelium of these mice show that NO plays a significant role in modulating adaptation. Evidence for the presence of eNOS in mature mammalian OSNs and its involvement in odorant adaptation implicates NO as an important new element involved in olfactory signal transduction. As a diffusible messenger, NO could also have additional functions related to cross adaptation, regeneration, and maintenance of MOE homeostasis. PMID:19430528

  6. Olfactory impairment in an adult population: the Beaver Dam Offspring Study.

    PubMed

    Schubert, Carla R; Cruickshanks, Karen J; Fischer, Mary E; Huang, Guan-Hua; Klein, Barbara E K; Klein, Ronald; Pankow, James S; Nondahl, David M

    2012-05-01

    The objective of this study was to determine the prevalence of olfactory impairment and associated risk factors and the effects of olfactory impairment on dietary choices and quality of life. Odor identification was measured in 2838 participants aged 21-84 years (mean 49 years) in the Beaver Dam Offspring Study. The overall prevalence of olfactory impairment was 3.8%, increased with age (from 0.6% in those<35 years to 13.9% among those≥65 years) and was more common in men than women. In a multivariate model age (odds ratio [OR]=1.48, 95% confidence interval [CI]=1.33, 1.64 for every 5-year increase), nasal polyps or deviated septum (OR=2.69, 95% CI=1.62, 4.48), ankle-brachial index<0.9 (OR=3.62, 95% CI=1.45, 9.01), and smoking (women only) (OR=2.43, 95% CI=1.19, 4.98 ever smoked vs. never) were associated with an increased odds of olfactory impairment, whereas higher household income, ≥$50,000 versus <$50,000 per year, was associated with a decreased odds of olfactory impairment (OR=0.48, 95% CI=0.31, 0.73). Participants with olfactory impairment were less likely to report that food tasted as good as it used to, or that they experienced food flavors the same. There was no association between olfactory impairment and general health-related quality of life, depressive symptoms, or dietary choices. The prevalence of olfactory impairment was low in this largely middle-aged cohort, and some factors associated with olfactory impairment are potentially modifiable.

  7. Impact of actin filament stabilization on adult hippocampal and olfactory bulb neurogenesis.

    PubMed

    Kronenberg, Golo; Gertz, Karen; Baldinger, Tina; Kirste, Imke; Eckart, Sarah; Yildirim, Ferah; Ji, Shengbo; Heuser, Isabella; Schröck, Helmut; Hörtnagl, Heide; Sohr, Reinhard; Djoufack, Pierre Chryso; Jüttner, René; Glass, Rainer; Przesdzing, Ingo; Kumar, Jitender; Freyer, Dorette; Hellweg, Rainer; Kettenmann, Helmut; Fink, Klaus Benno; Endres, Matthias

    2010-03-03

    Rearrangement of the actin cytoskeleton is essential for dynamic cellular processes. Decreased actin turnover and rigidity of cytoskeletal structures have been associated with aging and cell death. Gelsolin is a Ca(2+)-activated actin-severing protein that is widely expressed throughout the adult mammalian brain. Here, we used gelsolin-deficient (Gsn(-/-)) mice as a model system for actin filament stabilization. In Gsn(-/-) mice, emigration of newly generated cells from the subventricular zone into the olfactory bulb was slowed. In vitro, gelsolin deficiency did not affect proliferation or neuronal differentiation of adult neural progenitors cells (NPCs) but resulted in retarded migration. Surprisingly, hippocampal neurogenesis was robustly induced by gelsolin deficiency. The ability of NPCs to intrinsically sense excitatory activity and thereby implement coupling between network activity and neurogenesis has recently been established. Depolarization-induced [Ca(2+)](i) increases and exocytotic neurotransmitter release were enhanced in Gsn(-/-) synaptosomes. Importantly, treatment of Gsn(-/-) synaptosomes with mycotoxin cytochalasin D, which, like gelsolin, produces actin disassembly, decreased enhanced Ca(2+) influx and subsequent exocytotic norepinephrine release to wild-type levels. Similarly, depolarization-induced glutamate release from Gsn(-/-) brain slices was increased. Furthermore, increased hippocampal neurogenesis in Gsn(-/-) mice was associated with a special microenvironment characterized by enhanced density of perfused vessels, increased regional cerebral blood flow, and increased endothelial nitric oxide synthase (NOS-III) expression in hippocampus. Together, reduced filamentous actin turnover in presynaptic terminals causes increased Ca(2+) influx and, subsequently, elevated exocytotic neurotransmitter release acting on neural progenitors. Increased neurogenesis in Gsn(-/-) hippocampus is associated with a special vascular niche for neurogenesis.

  8. Dynamic expression of the polysialyltransferase in adult rat hippocampus performing an olfactory associative task.

    PubMed

    Manrique, Christine; Migliorati, Martine; Gilbert, Valérie; Brezun, Jean-Michel; Chaillan, Franck A; Truchet, Bruno; Khrestchatisky, Michel; Guiraudie-Capraz, Gaëlle; Roman, François S

    2014-08-01

    Neural cell adhesion molecule (NCAM) is associated with polysialic acid (PSA), and its function is highly dependent on the extent of polysialylation through the activity of two polysialyltransferases, sialyltransferase-X (STX) and polysialyltransferase (PST). PSA-NCAM plays an important role in synaptic plasticity in the hippocampus. The involvement of STX and PST during mnesic processes was assessed in the adult rat hippocampus. We investigated whether different levels in learning and memory using an olfactory associative task influenced STX and PST gene expression in the hippocampus using semiquantitative transcription-polymerase chain reaction. Then, NCAM polysialylation and cell proliferation were quantified in the dentate gyrus of a "Learning and Memory" group using immunohistochemistry. We found that only the expression level of PST mRNA increased with learning performance and returned to an initial level when learned associations were consolidated in long-term memory, while STX mRNA levels remained unchanged. This phenomenon was accompanied by an increase in PSA on NCAM but not by cell proliferation in the dentate gyrus. Our results suggest a different involvement for STX and PST in neural plasticity: while STX is probably involved in the proliferation of neural progenitor cells, PST could play a key role in synaptic plasticity of mature neural networks. The expression of the STX and PST genes could, therefore, be useful markers of neurobiological plasticity in the brain, allowing to follow chronological events in limbic and cortical structures related first to learning and memory processes (for PST) and, second, to adult neurogenesis processes (for STX).

  9. Differential expression of TYRP1 in adult human retinal pigment epithelium and uveal melanoma cells

    PubMed Central

    QIU, CHUN; LI, PENG; BI, JIANJUN; WU, QING; LU, LINNA; QIAN, GUANXIANG; JIA, RENBING; JIA, RONG

    2016-01-01

    Uveal melanoma (UM) is the most frequently occurring primary intraocular malignancy in adults. Tyrosinase (TYR) is a copper-containing enzyme and a type I membrane protein that is involved in the generation of melanin, the main pigment in vertebrates. TYR-related protein 1 (TYRP1) is regarded to have a crucial role in the immunotherapy of melanoma. As biomarkers, the TYR-related proteins, TYRP1 and TYRP2, exhibit specific expression in melanocytes, while also contributing to melanin synthesis within melanosomes. In the present study, the differential expression of TYRP1 was investigated at the mRNA, protein and morphological levels in four human UM cell lines (SP6.5, OM431, OCM1 and OCM290) and the human retinal pigment epithelium (RPE) cell line, using polymerase chain reaction, western blotting, immunocytochemistry and immunofluorescence staining. It was found that SP6.5 cells expressed the highest level of TYRP1, in comparison to SP6.5 OCM1 and OM431 cells, which produced less TYRP1, and OCM290 cells, which produced almost no TYRP1. No TYRP1 protein expression was identified in the RPE cell line. These findings indicate the potential use of TYRP1 in the development of therapy for UM. PMID:27073483

  10. Morphological and molecular features of the mammalian olfactory sensory neuron axons: What makes these axons so special?

    PubMed

    Nedelec, Stéphane; Dubacq, Caroline; Trembleau, Alain

    2005-03-01

    The main organization and gross morphology of the mammalian olfactory primary pathway, from the olfactory epithelium to the olfactory bulb, has been initially characterized using classical anatomical and ultrastructural approaches. During the last fifteen years, essentially thanks to the cloning of the odorant receptor genes, and to the characterization of a number of molecules expressed by the olfactory sensory neuron axons and their environment, significant new insights have been gained into the understanding of the development and adult functioning of this system. In the course of these genetic, biochemical and neuroanatomical studies, however, several molecular and structural features were uncovered that appear somehow to be unique to these axons. For example, these axons express odorant receptors in their terminal segment, and transport several mRNA species and at least two transcription factors. In the present paper, we review these unusual structural and molecular features and speculate about their possible functions in the development and maintenance of the olfactory system.

  11. The olfactory apparatus of the bandicoot (Isoodon macrourus): fine structure and presence of a septal olfactory organ.

    PubMed Central

    Kratzing, J E

    1978-01-01

    The structure and extent of olfactory epithelium in the bandicoot (Isoodon macrourus) were examined by light and electron microscopy. Sensory epithelium covers most of the dorsal conchae, though non-sensory epithelium lines ventrally facing scrolls. The middle conchae are partly covered by olfactory epithelium, the proportion of olfactory to ciliated respiratory epithelium increasing caudally. Ventral conchae are lined by non-sensory ciliated epithelium. The nasal septum ends short of the floor of the nasal cavity in its caudal two thirds. It is covered dorsally by olfactory epithelium. The ventral margin has rounded lateral extensions which carry the isolated strips of olfactory epithelium which form the septal olfactory organ. The fine structure of the olfactory epithelium is the same in all areas. Cell types include olfactory receptors, supporting cells, two types of basal cell and rarer pale and brush cells. There is considerable morphological variation in olfactory cells, and evidence suggestive of continuing turnover in the receptor cell population. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 PMID:640961

  12. The seminiferous epithelium cycle and daily spermatic production in the adult maned wolf (Chrysocyon brachyurus, Illiger, 1811).

    PubMed

    Bitencourt, Viviane Lewicki; de Paula, Tarcízio Antônio Rego; da Matta, Sérgio Luis Pinto; Fonseca, Cláudio César; dos Anjos Benjamin, Laércio; Costa, Deiler Sampaio

    2007-01-01

    The duration of the seminiferous epithelium cycle was estimated in adult maned wolves (Chrysocyon brachyurus, Illiger, 1811), by applying intratesticular injections with tritiated thymidine. The total duration of the seminiferous epithelium cycle in this species was calculated in 8.99 days. So, taking into account that approximately 4.5 cycles of the seminiferous epithelium are necessary for the whole spermatogenesis process to complete, the production of spermatozoa from one spermatogonia will take about 40.45 days. The duration of the spermiogenesis was calculated to be 12.3 days. The eight stages of the seminiferous epithelium cycle were described by the tubular morphology method, which is based either on the form and position of the spermatid nuclei and the occurrence of meiotic divisions. The values of the relative frequency for the pre-meiotic, meiotic and post-meiotic phases in this species were 3.5, 0.78 and 4.8 days, respectively. The maned wolf produces about 29 million spermatozoa a day for each testis gram, therefore being classified among the species provided with a high spermatogenetic efficiency.

  13. Sonic hedgehog acts as a negative regulator of {beta}-catenin signaling in the adult tongue epithelium.

    PubMed

    Schneider, Fabian T; Schänzer, Anne; Czupalla, Cathrin J; Thom, Sonja; Engels, Knut; Schmidt, Mirko H H; Plate, Karl H; Liebner, Stefan

    2010-07-01

    Wnt/beta-catenin signaling has been implicated in taste papilla development; however, its role in epithelial maintenance and tumor progression in the adult tongue remains elusive. We show Wnt/beta-catenin pathway activation in reporter mice and by nuclear beta-catenin staining in the epithelium and taste papilla of adult mouse and human tongues. beta-Catenin activation in APC(min/+) mice, which carry a mutation in adenomatous poliposis coli (APC), up-regulates Sonic hedgehog (Shh) and Jagged-2 (JAG2) in the tongue epithelium without formation of squamous cell carcinoma (SCC). We demonstrate that Shh suppresses beta-catenin transcriptional activity in a signaling-dependent manner in vitro and in vivo. A similar regulation and function was observed for JAG2, suggesting that both pathways negatively regulate beta-catenin, thereby preventing SCC formation in the tongue. This was supported by reduced nuclear beta-catenin in the tongue epithelium of Patched(+/-) mice, exhibiting dominant active Shh signaling. At the invasive front of human tongue cancer, nuclear beta-catenin and Shh were increased, suggesting their participation in tumor progression. Interestingly, Shh but not JAG2 was able to reduce beta-catenin signaling in SCC cells, arguing for a partial loss of negative feedback on beta-catenin transcription in tongue cancer. We show for the first time that the putative Wnt/beta-catenin targets Shh and JAG2 control beta-catenin signaling in the adult tongue epithelium, a function that is partially lost in lingual SCC.

  14. Sonic Hedgehog Acts as a Negative Regulator of β-Catenin Signaling in the Adult Tongue Epithelium

    PubMed Central

    Schneider, Fabian T.; Schänzer, Anne; Czupalla, Cathrin J.; Thom, Sonja; Engels, Knut; Schmidt, Mirko H.H.; Plate, Karl H.; Liebner, Stefan

    2010-01-01

    Wnt/β-catenin signaling has been implicated in taste papilla development; however, its role in epithelial maintenance and tumor progression in the adult tongue remains elusive. We show Wnt/β-catenin pathway activation in reporter mice and by nuclear β-catenin staining in the epithelium and taste papilla of adult mouse and human tongues. β-Catenin activation in APCmin/+ mice, which carry a mutation in adenomatous poliposis coli (APC), up-regulates Sonic hedgehog (Shh) and Jagged-2 (JAG2) in the tongue epithelium without formation of squamous cell carcinoma (SCC). We demonstrate that Shh suppresses β-catenin transcriptional activity in a signaling-dependent manner in vitro and in vivo. A similar regulation and function was observed for JAG2, suggesting that both pathways negatively regulate β-catenin, thereby preventing SCC formation in the tongue. This was supported by reduced nuclear β-catenin in the tongue epithelium of Patched+/− mice, exhibiting dominant active Shh signaling. At the invasive front of human tongue cancer, nuclear β-catenin and Shh were increased, suggesting their participation in tumor progression. Interestingly, Shh but not JAG2 was able to reduce β-catenin signaling in SCC cells, arguing for a partial loss of negative feedback on β-catenin transcription in tongue cancer. We show for the first time that the putative Wnt/β-catenin targets Shh and JAG2 control β-catenin signaling in the adult tongue epithelium, a function that is partially lost in lingual SCC. PMID:20508033

  15. Fluoro Jade-B detection of dying cells in the SVZ and RMS of adult rats after bilateral olfactory bulbectomy.

    PubMed

    Mitrusková, Barbora; Orendácová, Judita; Raceková, Enikö

    2005-12-01

    A novel fluorochrome, Fluoro-Jade B, was used to detect dying precursor cells in the subventricular zone (SVZ) and rostral migratory stream (RMS) of adult rats after bilateral olfactory bulbectomy and in control intact rats. The animals in experimental group were left to survive 3 days and from 3 till 16 months after surgical procedure. 1. In the control animals, Fluoro-Jade B positive cells were visible in the SVZ and within the whole extent of the RMS. The number of Fluoro-Jade B positive cells increased in the elbow in comparison to the rest parts of the RMS. 2. In the experimental animals surviving either 3 days or from 3 till 16 months after bilateral olfactory bulbectomy, Fluoro-Jade B positive cells displayed the similar pattern of distribution as in the control animals. However, some quantitative differences in the labeled cells number along the rostral migratory pathway appeared. 3. The average number of degenerating cells within the control SVZ and RMS was 26.24+/- 0.686. In bulbectomized animals, regardless of survival time, an insignificant increase of Fluoro-Jade B positive cells number occurred. We can conclude that dying of precursor cells is a physiological process running within the SVZ/RMS in both control and experimental animals. Moreover, this physiological process is not influenced by survival period after bilateral olfactory bulbectomy. Our results demonstrate Fluoro-Jade B as a useful marker of dying cells.

  16. Anosmin-1 over-expression increases adult neurogenesis in the subventricular zone and neuroblast migration to the olfactory bulb.

    PubMed

    García-González, Diego; Murcia-Belmonte, Verónica; Esteban, Pedro F; Ortega, Felipe; Díaz, David; Sánchez-Vera, Irene; Lebrón-Galán, Rafael; Escobar-Castañondo, Laura; Martínez-Millán, Luis; Weruaga, Eduardo; García-Verdugo, José Manuel; Berninger, Benedikt; de Castro, Fernando

    2016-01-01

    New subventricular zone (SVZ)-derived neuroblasts that migrate via the rostral migratory stream are continuously added to the olfactory bulb (OB) of the adult rodent brain. Anosmin-1 (A1) is an extracellular matrix protein that binds to FGF receptor 1 (FGFR1) to exert its biological effects. When mutated as in Kallmann syndrome patients, A1 is associated with severe OB morphogenesis defects leading to anosmia and hypogonadotropic hypogonadism. Here, we show that A1 over-expression in adult mice strongly increases proliferation in the SVZ, mainly with symmetrical divisions, and produces substantial morphological changes in the normal SVZ architecture, where we also report the presence of FGFR1 in almost all SVZ cells. Interestingly, for the first time we show FGFR1 expression in the basal body of primary cilia in neural progenitor cells. Additionally, we have found that A1 over-expression also enhances neuroblast motility, mainly through FGFR1 activity. Together, these changes lead to a selective increase in several GABAergic interneuron populations in different OB layers. These specific alterations in the OB would be sufficient to disrupt the normal processing of sensory information and consequently alter olfactory memory. In summary, this work shows that FGFR1-mediated A1 activity plays a crucial role in the continuous remodelling of the adult OB.

  17. Deep Sequencing of the Murine Olfactory Receptor Neuron Transcriptome

    PubMed Central

    Kanageswaran, Ninthujah; Demond, Marilen; Nagel, Maximilian; Schreiner, Benjamin S. P.; Baumgart, Sabrina; Scholz, Paul; Altmüller, Janine; Becker, Christian; Doerner, Julia F.; Conrad, Heike; Oberland, Sonja; Wetzel, Christian H.; Neuhaus, Eva M.; Hatt, Hanns; Gisselmann, Günter

    2015-01-01

    The ability of animals to sense and differentiate among thousands of odorants relies on a large set of olfactory receptors (OR) and a multitude of accessory proteins within the olfactory epithelium (OE). ORs and related signaling mechanisms have been the subject of intensive studies over the past years, but our knowledge regarding olfactory processing remains limited. The recent development of next generation sequencing (NGS) techniques encouraged us to assess the transcriptome of the murine OE. We analyzed RNA from OEs of female and male adult mice and from fluorescence-activated cell sorting (FACS)-sorted olfactory receptor neurons (ORNs) obtained from transgenic OMP-GFP mice. The Illumina RNA-Seq protocol was utilized to generate up to 86 million reads per transcriptome. In OE samples, nearly all OR and trace amine-associated receptor (TAAR) genes involved in the perception of volatile amines were detectably expressed. Other genes known to participate in olfactory signaling pathways were among the 200 genes with the highest expression levels in the OE. To identify OE-specific genes, we compared olfactory neuron expression profiles with RNA-Seq transcriptome data from different murine tissues. By analyzing different transcript classes, we detected the expression of non-olfactory GPCRs in ORNs and established an expression ranking for GPCRs detected in the OE. We also identified other previously undescribed membrane proteins as potential new players in olfaction. The quantitative and comprehensive transcriptome data provide a virtually complete catalogue of genes expressed in the OE and present a useful tool to uncover candidate genes involved in, for example, olfactory signaling, OR trafficking and recycling, and proliferation. PMID:25590618

  18. Evidence of progenitor cells of glandular and myoepithelial cell lineages in the human adult female breast epithelium: a new progenitor (adult stem) cell concept.

    PubMed

    Boecker, Werner; Buerger, Horst

    2003-10-01

    Although experimental data clearly confirm the existence of self-renewing mammary stem cells, the characteristics of such progenitor cells have never been satisfactorily defined. Using a double immunofluorescence technique for simultaneous detection of the basal cytokeratin 5, the glandular cytokeratins 8/18 and the myoepithelial differentiation marker smooth muscle actin (SMA), we were able to demonstrate the presence of CK5+ cells in human adult breast epithelium. These cells have the potential to differentiate to either glandular (CK8/18+) or myoepithelial cells (SMA+) through intermediary cells (CK5+ and CK8/18+ or SMA+). We therefore proceeded on the assumption that the CK5+ cells are phenotypically and behaviourally progenitor (committed adult stem) cells of human breast epithelium. Furthermore, we furnish evidence that most of these progenitor cells are located in the luminal epithelium of the ductal lobular tree. Based on data obtained in extensive analyses of proliferative breast disease lesions, we have come to regard usual ductal hyperplasia as a progenitor cell-derived lesion, whereas most breast cancers seem to evolve from differentiated glandular cells. Double immunofluorescence experiments provide a new tool to characterize phenotypically progenitor (adult stem) cells and their progenies. This model has been shown to be of great value for a better understanding not only of normal tissue regeneration but also of proliferative breast disease. Furthermore, this model provides a new tool for unravelling further the regulatory mechanisms that govern normal and pathological cell growth.

  19. Urban air pollution: influences on olfactory function and pathology in exposed children and young adults.

    PubMed

    Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; Henríquez-Roldán, Carlos; Osnaya, Norma; González-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderon, Rafael; Herritt, Lou; Brooks, Diane; Keefe, Sheyla; Palacios-Moreno, Juan; Villarreal-Calderon, Rodolfo; Torres-Jardón, Ricardo; Medina-Cortina, Humberto; Delgado-Chávez, Ricardo; Aiello-Mora, Mario; Maronpot, Robert R; Doty, Richard L

    2010-01-01

    Mexico City (MC) residents are exposed to severe air pollution and exhibit olfactory bulb inflammation. We compared the olfactory function of individuals living under conditions of extreme air pollution to that of controls from a relatively clean environment and explore associations between olfaction scores, apolipoprotein E (APOE) status, and pollution exposure. The olfactory bulbs (OBs) of 35 MC and 9 controls 20.8+/-8.5 years were assessed by light and electron microscopy. The University of Pennsylvania Smell Identification Test (UPSIT) was administered to 62 MC/25 controls 21.2+/-2.7 years. MC subjects had significantly lower UPSIT scores: 34.24+/-0.42 versus controls 35.76+/-0.40, p=0.03. Olfaction deficits were present in 35.5% MC and 12% of controls. MC APOE epsilon 4 carriers failed 2.4+/-0.54 items in the 10-item smell identification scale from the UPSIT related to Alzheimer's disease, while APOE 2/3 and 3/3 subjects failed 1.36+/-0.16 items, p=0.01. MC residents exhibited OB endothelial hyperplasia, neuronal accumulation of particles (2/35), and immunoreactivity to beta amyloid betaA(42) (29/35) and/or alpha-synuclein (4/35) in neurons, glial cells and/or blood vessels. Ultrafine particles were present in OBs endothelial cytoplasm and basement membranes. Control OBs were unremarkable. Air pollution exposure is associated with olfactory dysfunction and OB pathology, APOE 4 may confer greater susceptibility to such abnormalities, and ultrafine particles could play a key role in the OB pathology. This study contributes to our understanding of the influences of air pollution on olfaction and its potential contribution to neurodegeneration.

  20. Electrophysiological Evidence for a Direct Link between the Main and Accessory Olfactory Bulbs in the Adult Rat

    PubMed Central

    Vargas-Barroso, Victor; Ordaz-Sánchez, Benito; Peña-Ortega, Fernando; Larriva-Sahd, Jorge A.

    2016-01-01

    It is accepted that the main- and accessory- olfactory systems exhibit overlapping responses to pheromones and odorants. We performed whole-cell patch-clamp recordings in adult rat olfactory bulb slices to define a possible interaction between the first central relay of these systems: the accessory olfactory bulb (AOB) and the main olfactory bulb (MOB). This was tested by applying electrical field stimulation in the dorsal part of the MOB while recording large principal cells (LPCs) of the anterior AOB (aAOB). Additional recordings of LPCs were performed at either side of the plane of intersection between the aAOB and posterior-AOB (pAOB) halves, or linea alba, while applying field stimulation to the opposite half. A total of 92 recorded neurons were filled during whole-cell recordings with biocytin and studied at the light microscope. Neurons located in the aAOB (n = 6, 8%) send axon collaterals to the MOB since they were antidromically activated in the presence of glutamate receptor antagonists (APV and CNQX). Recorded LPCs evoked orthodromic excitatory post-synaptic responses (n = 6, aAOB; n = 1, pAOB) or antidromic action potentials (n = 8, aAOB; n = 7, pAOB) when applying field stimulation to the opposite half of the recording site (e.g., recording in aAOB; stimulating in pAOB, and vice-versa). Observation of the filled neurons revealed that indeed, LPCs send axon branches that cross the linea alba to resolve in the internal cellular layer. Additionally, LPCs of the aAOB send axon collaterals to dorsal-MOB territory. Notably, while performing AOB recordings we found a sub-population of neurons (24% of the total) that exhibited voltage-dependent bursts of action potentials. Our findings support the existence of: 1. a direct projection from aAOB LPCs to dorsal-MOB, 2. physiologically active synapses linking aAOB and pAOB, and 3. pacemaker-like neurons in both AOB halves. This work was presented in the form of an Abstract on SfN 2014 (719.14/EE17). PMID:26858596

  1. Identification of the Ulex europaeus agglutinin-I-binding protein as a unique glycoform of the neural cell adhesion molecule in the olfactory sensory axons of adults rats.

    PubMed

    Pestean, A; Krizbai, I; Böttcher, H; Párducz, A; Joó, F; Wolff, J R

    1995-08-04

    Histochemical localization of two lectins, Ulex europaeus agglutinin-I (UEA-I) and Tetragonolobus purpureus (TPA), was studied in the olfactory bulb of adult rats. In contrast to TPA, UEA-I detected a fucosylated glycoprotein that is only present in the surface membranes of olfactory sensory cells including the whole course of their neurites up to the final arborization in glomeruli. Immunoblotting revealed that UEA-I binds specifically to a protein of 205 kDa, while TPA stains several other glycoproteins. Affinity chromatography with the use of a UEA-I column identified the 205 kDa protein as a glycoform of neural cell adhesion molecule (N-CAM), specific for the rat olfactory sensory nerves.

  2. Analysis of glycoproteins produced by the associated gland in the olfactory organ of lungfish.

    PubMed

    Nakamuta, Nobuaki; Nakamuta, Shoko; Taniguchi, Kazumi; Taniguchi, Kazuyuki

    2013-07-31

    The olfactory organ of African lungfish, Protopterus annectens, contains two distinct sensory epithelia: the lamellar olfactory epithelium and the recess epithelium. These epithelia correspond to the olfactory epithelium and the vomeronasal organ of tetrapods, respectively. In contrast to the lamellar olfactory epithelium, which has no associated gland, the recess epithelium is equipped with associated glands. Although the glandular cells and/or the supporting cells are generally presumed to secrete proteins involved in the function of olfactory sensory epithelia, the properties of these proteins in lungfish have not been evaluated to date. In this study, we investigated the associated glands in the olfactory organ of lungfish by transmission electron microscopy and found that the glandular cells contain numerous secretory granules and secrete them from the apical membrane. In addition, we analyzed the olfactory organ by lectin histochemistry using 16 biotinylated lectins. All lectins labeled the secretory granules in the glandular cells with different staining patterns from those of the supporting cells in the lamellar olfactory epithelium or in the recess epithelium. Furthermore, lectin blotting analysis showed that multiple bands were detected by the lectins which specifically labeled the glandular epithelium of the olfactory organ. These results indicate that the secretory products of the associated glands in the recess epithelium have different properties from those of the supporting cells in the olfactory sensory epithelia and contain multiple glycoproteins with different carbohydrate moieties.

  3. Adult Human Olfactory Epithelial-Derived Progenitors: A Potential Autologous Source for Cell-Based Treatment for Parkinson's Disease

    PubMed Central

    Wang, Meng; Lu, Chengliang

    2012-01-01

    Human adult olfactory epithelial-derived neural progenitors (hONPs) can differentiate along several neural lineages in response to morphogenic signals in vitro. A previous study optimized the transfection paradigm for the differentiation of hONPs to dopaminergic neurons. This study engrafted cells modified by the most efficient transfection paradigm for dopaminergic neural restriction and pretransfected controls into a unilateral neurotoxin, 6-hydroxydopamine-induced parkinsonian rat model. Approximately 35% of the animals engrafted with hONPs had improved behavioral recovery as demonstrated by the amphetamine-induced rotation test, as well as a corner preference and cylinder paw preference, over a period of 24 weeks. The pre- and post-transfected groups produced equivalent responses, indicating that the toxic host environment supported hONP dopaminergic differentiation in situ. Human fibroblasts used as a cellular control did not diminish the parkinsonian rotational deficits at any point during the study. Increased numbers of tyrosine hydroxylase (TH)-positive cells were detected in the engrafted brains compared with the fibroblast-implanted and medium-only controls. Engrafted TH-positive hONPs were detected for a minimum of 6 months in vivo; they were multipolar, had long processes, and migrated beyond their initial injection sites. Higher dopamine levels were detected in the striatum of behaviorally improved animals than in equivalent regions of their nonrecovered counterparts. Throughout these experiments, no evidence of tumorigenicity was observed. These results support our hypothesis that human adult olfactory epithelial-derived progenitors represent a unique autologous cell type with promising potential for future use in a cell-based therapy for patients with Parkinson's disease. PMID:23197853

  4. Olfactory Thresholds of the U.S. Population of Home-Dwelling Older Adults: Development and Validation of a Short, Reliable Measure

    PubMed Central

    Kern, David W.; Schumm, L. Philip; Wroblewski, Kristen E.; Pinto, Jayant M.; Hummel, Thomas; McClintock, Martha K.

    2015-01-01

    Current methods of olfactory sensitivity testing are logistically challenging and therefore infeasible for use in in-home surveys and other field settings. We developed a fast, easy and reliable method of assessing olfactory thresholds, and used it in the first study of olfactory sensitivity in a nationally representative sample of U.S. home-dwelling older adults. We validated our method via computer simulation together with a model estimated from 590 normosmics. Simulated subjects were assigned n-butanol thresholds drawn from the estimated normosmic distribution and based on these and the model, we simulated administration of both the staircase and constant stimuli methods. Our results replicate both the correlation between the two methods and their reliability as previously reported by studies using human subjects. Further simulations evaluated the reliability of different constant stimuli protocols, varying both the range of dilutions and number of stimuli (6–16). Six appropriately chosen dilutions were sufficient for good reliability (0.67) in normosmic subjects. Finally, we applied our method to design a 5-minute, in-home assessment of older adults (National Social Life, Health and Aging Project, or NSHAP), which had comparable reliability (0.56), despite many subjects having estimated thresholds above the strongest dilution. Thus, testing with a fast, 6-item constant stimuli protocol is informative, and permits olfactory testing in previously inaccessible research settings. PMID:25768291

  5. Olfactory thresholds of the U.S. Population of home-dwelling older adults: development and validation of a short, reliable measure.

    PubMed

    Kern, David W; Schumm, L Philip; Wroblewski, Kristen E; Pinto, Jayant M; Hummel, Thomas; McClintock, Martha K

    2015-01-01

    Current methods of olfactory sensitivity testing are logistically challenging and therefore infeasible for use in in-home surveys and other field settings. We developed a fast, easy and reliable method of assessing olfactory thresholds, and used it in the first study of olfactory sensitivity in a nationally representative sample of U.S. home-dwelling older adults. We validated our method via computer simulation together with a model estimated from 590 normosmics. Simulated subjects were assigned n-butanol thresholds drawn from the estimated normosmic distribution and based on these and the model, we simulated administration of both the staircase and constant stimuli methods. Our results replicate both the correlation between the two methods and their reliability as previously reported by studies using human subjects. Further simulations evaluated the reliability of different constant stimuli protocols, varying both the range of dilutions and number of stimuli (6-16). Six appropriately chosen dilutions were sufficient for good reliability (0.67) in normosmic subjects. Finally, we applied our method to design a 5-minute, in-home assessment of older adults (National Social Life, Health and Aging Project, or NSHAP), which had comparable reliability (0.56), despite many subjects having estimated thresholds above the strongest dilution. Thus, testing with a fast, 6-item constant stimuli protocol is informative, and permits olfactory testing in previously inaccessible research settings.

  6. The olfactory system of migratory adult sea lamprey (Petromyzon marinus) is specifically and acutely sensitive to unique bile acids released by conspecific larvae

    PubMed Central

    1995-01-01

    Larval sea lamprey inhabit freshwater streams and migrate to oceans or lakes to feed after a radical metamorphosis; subsequently, mature adults return to streams to spawn. Previous observations suggested that lamprey utilize the odor of conspecific larvae to select streams for spawning. Here we report biochemical and electrophysiological evidence that this odor is comprised of two unique bile acids released by larvae. High performance liquid chromatography and mass spectrometry demonstrated that larval sea lamprey produce and release two unique bile acids, allocholic acid (ACA) and petromyzonol sulfate (PS). Electro-olfactogram (EOG) recording also demonstrated that the olfactory system of migratory adult sea lamprey is acutely and specifically sensitive to ACA and PS; detection thresholds for these compounds were approximately 10(-12) M. ACA and PS were the most potent of 38 bile acids tested and cross-adaptation experiments suggested that adult sea lamprey have specific olfactory receptor sites associated with independent signal transduction pathways for these bile acids. These receptor sites specifically recognize the key substituents of ACA and PS such as a 5 alpha-hydrogen, three axial hydroxyls, and a C-24 sulfate ester or carboxyl. In conclusion, the unique lamprey bile acids, ACA and PS, are potent and specific stimulants of the adult olfactory system, strongly supporting the hypothesis that these unique bile acids function as migratory pheromones in lamprey. PMID:7658193

  7. Opposite-sex attraction in male mice requires testosterone-dependent regulation of adult olfactory bulb neurogenesis

    PubMed Central

    Schellino, Roberta; Trova, Sara; Cimino, Irene; Farinetti, Alice; Jongbloets, Bart C.; Pasterkamp, R. Jeroen; Panzica, Giancarlo; Giacobini, Paolo; De Marchis, Silvia; Peretto, Paolo

    2016-01-01

    Opposite-sex attraction in most mammals depends on the fine-tuned integration of pheromonal stimuli with gonadal hormones in the brain circuits underlying sexual behaviour. Neural activity in these circuits is regulated by sensory processing in the accessory olfactory bulb (AOB), the first central station of the vomeronasal system. Recent evidence indicates adult neurogenesis in the AOB is involved in sex behaviour; however, the mechanisms underlying this function are unknown. By using Semaphorin 7A knockout (Sema7A ko) mice, which show a reduced number of gonadotropin-releasing-hormone neurons, small testicles and subfertility, and wild-type males castrated during adulthood, we demonstrate that the level of circulating testosterone regulates the sex-specific control of AOB neurogenesis and the vomeronasal system activation, which influences opposite-sex cue preference/attraction in mice. Overall, these data highlight adult neurogenesis as a hub for the integration of pheromonal and hormonal cues that control sex-specific responses in brain circuits. PMID:27782186

  8. A preliminary study on the potential of Mycoplasma pneumoniae to induce dyskaryotic change in respiratory epithelium in adult community-acquired pneumonia

    PubMed Central

    An, Shu-Chang; Yang, Dong-Hong; Luo, Chao-Feng; Chen, Xin; Liu, Guo-Tian; Weng, Yan; Liu, Jing-Zhe; Shang, Ying; Wang, Rui-Qin; Gao, Zhan-Cheng

    2016-01-01

    Background: This study aimed to explore the cellular morphology of respiratory epithelium in Mycoplasma pneumonia (MpP) patients. Materials and Methods: The cast-off cell morphological findings from bronchoscopic brushings in MpP and community-acquired pneumonia (CAP) caused by typical pathogens were reviewed. Results: Compared with the CAP group, cellular dysplasia in respiratory tract epithelial brushings was significantly greater in MpP patients (P = 0.033). Conclusion: Unique biological characteristics and mechanisms of pathogenesis of Mycoplasma pneumoniae (Mp) may result in dyskaryotic changes in respiratory epithelium in adult MpP. PMID:28163727

  9. Functional and Molecular Characterization of Rod-like Cells from Retinal Stem Cells Derived from the Adult Ciliary Epithelium

    PubMed Central

    Demontis, Gian Carlo; Aruta, Claudia; Comitato, Antonella; De Marzo, Anna; Marigo, Valeria

    2012-01-01

    In vitro generation of photoreceptors from stem cells is of great interest for the development of regenerative medicine approaches for patients affected by retinal degeneration and for high throughput drug screens for these diseases. In this study, we show unprecedented high percentages of rod-fated cells from retinal stem cells of the adult ciliary epithelium. Molecular characterization of rod-like cells demonstrates that they lose ciliary epithelial characteristics but acquire photoreceptor features. Rod maturation was evaluated at two levels: gene expression and electrophysiological functionality. Here we present a strong correlation between phototransduction protein expression and functionality of the cells in vitro. We demonstrate that in vitro generated rod-like cells express cGMP-gated channels that are gated by endogenous cGMP. We also identified voltage-gated channels necessary for rod maturation and viability. This level of analysis for the first time provides evidence that adult retinal stem cells can generate highly homogeneous rod-fated cells. PMID:22432014

  10. Tumorigenic Potential of Olfactory Bulb-Derived Human Adult Neural Stem Cells Associates with Activation of TERT and NOTCH1

    PubMed Central

    Ricci-Vitiani, Lucia; Cenciarelli, Carlo; Petrucci, Giovanna; Milazzo, Luisa; Montano, Nicola; Tabolacci, Elisabetta; Maira, Giulio; Larocca, Luigi M.; Pallini, Roberto

    2009-01-01

    Background Multipotent neural stem cells (NSCs) have been isolated from neurogenic regions of the adult brain. Reportedly, these cells can be expanded in vitro under prolonged mitogen stimulation without propensity to transform. However, the constitutive activation of the cellular machinery required to bypass apoptosis and senescence places these cells at risk for malignant transformation. Methodology/Principal Findings Using serum-free medium supplemented with epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF), we established clonally derived NS/progenitor cell (NS/PC) cultures from the olfactory bulb (OB) of five adult patients. The NS/PC cultures obtained from one OB specimen lost growth factor dependence and neuronal differentiation at early passage. These cells developed glioblastoma tumors upon xenografting in immunosuppressed mice. The remaining NS/PC cultures were propagated either as floating neurospheres or as adherent monolayers with mainteinance of growth factor dependence and multipotentiality at late passage. These cells were engrafted onto the CNS of immunosuppressed rodents. Overall, the grafted NS/PCs homed in the host parenchyma showing ramified morphology and neuronal marker expression. However, a group of animals transplanted with NS/PCs obtained from an adherent culture developed fast growing tumors histologically resembling neuroesthesioblastoma. Cytogenetic and molecular analyses showed that the NS/PC undergo chromosomal changes with repeated in vitro passages under mitogen stimulation, and that up-regulation of hTERT and NOTCH1 associates with in vivo tumorigenicity. Conclusions/Significance Using culturing techniques described in current literature, NS/PCs arise from the OB of adult patients which in vivo either integrate in the CNS parenchyma showing neuron-like features or initiate tumor formation. Extensive xenografting studies on each human derived NS cell line appear mandatory before any use of these cells in the

  11. Anatomy, histochemistry, and immunohistochemistry of the olfactory subsystems in mice.

    PubMed

    Barrios, Arthur W; Núñez, Gonzalo; Sánchez Quinteiro, Pablo; Salazar, Ignacio

    2014-01-01

    The four regions of the murine nasal cavity featuring olfactory neurons were studied anatomically and by labeling with lectins and relevant antibodies with a view to establishing criteria for the identification of olfactory subsystems that are readily applicable to other mammals. In the main olfactory epithelium and the septal organ the olfactory sensory neurons (OSNs) are embedded in quasi-stratified columnar epithelium; vomeronasal OSNs are embedded in epithelium lining the medial interior wall of the vomeronasal duct and do not make contact with the mucosa of the main nasal cavity; and in Grüneberg's ganglion a small isolated population of OSNs lies adjacent to, but not within, the epithelium. With the exception of Grüneberg's ganglion, all the tissues expressing olfactory marker protein (OMP) (the above four nasal territories, the vomeronasal and main olfactory nerves, and the main and accessory olfactory bulbs) are also labeled by Lycopersicum esculentum agglutinin, while Ulex europaeus agglutinin I labels all and only tissues expressing Gαi2 (the apical sensory neurons of the vomeronasal organ, their axons, and their glomerular destinations in the anterior accessory olfactory bulb). These staining patterns of UEA-I and LEA may facilitate the characterization of olfactory anatomy in other species. A 710-section atlas of the anatomy of the murine nasal cavity has been made available on line.

  12. Anatomy, histochemistry, and immunohistochemistry of the olfactory subsystems in mice

    PubMed Central

    Barrios, Arthur W.; Núñez, Gonzalo; Sánchez Quinteiro, Pablo; Salazar, Ignacio

    2014-01-01

    The four regions of the murine nasal cavity featuring olfactory neurons were studied anatomically and by labeling with lectins and relevant antibodies with a view to establishing criteria for the identification of olfactory subsystems that are readily applicable to other mammals. In the main olfactory epithelium and the septal organ the olfactory sensory neurons (OSNs) are embedded in quasi-stratified columnar epithelium; vomeronasal OSNs are embedded in epithelium lining the medial interior wall of the vomeronasal duct and do not make contact with the mucosa of the main nasal cavity; and in Grüneberg's ganglion a small isolated population of OSNs lies adjacent to, but not within, the epithelium. With the exception of Grüneberg's ganglion, all the tissues expressing olfactory marker protein (OMP) (the above four nasal territories, the vomeronasal and main olfactory nerves, and the main and accessory olfactory bulbs) are also labeled by Lycopersicum esculentum agglutinin, while Ulex europaeus agglutinin I labels all and only tissues expressing Gαi2 (the apical sensory neurons of the vomeronasal organ, their axons, and their glomerular destinations in the anterior accessory olfactory bulb). These staining patterns of UEA-I and LEA may facilitate the characterization of olfactory anatomy in other species. A 710-section atlas of the anatomy of the murine nasal cavity has been made available on line. PMID:25071468

  13. Profiling of Olfactory Receptor Gene Expression in Whole Human Olfactory Mucosa

    PubMed Central

    Tarabichi, Maxime; Gregoire, Françoise; Dumont, Jacques E.; Chatelain, Pierre

    2014-01-01

    Olfactory perception is mediated by a large array of olfactory receptor genes. The human genome contains 851 olfactory receptor gene loci. More than 50% of the loci are annotated as nonfunctional due to frame-disrupting mutations. Furthermore haplotypic missense alleles can be nonfunctional resulting from substitution of key amino acids governing protein folding or interactions with signal transduction components. Beyond their role in odor recognition, functional olfactory receptors are also required for a proper targeting of olfactory neuron axons to their corresponding glomeruli in the olfactory bulb. Therefore, we anticipate that profiling of olfactory receptor gene expression in whole human olfactory mucosa and analysis in the human population of their expression should provide an opportunity to select the frequently expressed and potentially functional olfactory receptors in view of a systematic deorphanization. To address this issue, we designed a TaqMan Low Density Array (Applied Biosystems), containing probes for 356 predicted human olfactory receptor loci to investigate their expression in whole human olfactory mucosa tissues from 26 individuals (13 women, 13 men; aged from 39 to 81 years, with an average of 67±11 years for women and 63±12 years for men). Total RNA isolation, DNase treatment, RNA integrity evaluation and reverse transcription were performed for these 26 samples. Then 384 targeted genes (including endogenous control genes and reference genes specifically expressed in olfactory epithelium for normalization purpose) were analyzed using the same real-time reverse transcription PCR platform. On average, the expression of 273 human olfactory receptor genes was observed in the 26 selected whole human olfactory mucosa analyzed, of which 90 were expressed in all 26 individuals. Most of the olfactory receptors deorphanized to date on the basis of sensitivity to known odorant molecules, which are described in the literature, were found in the

  14. Gene Expression Profile of Adult Human Olfactory Bulb and Embryonic Neural Stem Cell Suggests Distinct Signaling Pathways and Epigenetic Control

    PubMed Central

    Marei, Hany E. S.; Ahmed, Abd-Elmaksoud; Michetti, Fabrizio; Pescatori, Mario; Pallini, Roberto; Casalbore, Patricia; Cenciarelli, Carlo; Elhadidy, Mohamed

    2012-01-01

    Global gene expression profiling was performed using RNA from human embryonic neural stem cells (hENSC), and adult human olfactory bulb-derived neural stem cells (OBNSCs), to define a gene expression pattern and signaling pathways that are specific for each cell lineage. We have demonstrated large differences in the gene expression profile of human embryonic NSC, and adult human OBNSCs, but less variability between parallel cultures. Transcripts of genes involved in neural tube development and patterning (ALDH1A2, FOXA2), progenitor marker genes (LMX1a, ALDH1A1, SOX10), proliferation of neural progenitors (WNT1 and WNT3a), neuroplastin (NPTN), POU3F1 (OCT6), neuroligin (NLGN4X), MEIS2, and NPAS1 were up-regulated in both cell populations. By Gene Ontology, 325 out of 3875 investigated gene sets were scientifically different. 41 out of the 307 investigated Cellular Component (CC) categories, 45 out of the 620 investigated Molecular Function (MF) categories, and 239 out of the 2948 investigated Biological Process (BP) categories were significant. KEGG Pathway Class Comparison had revealed that 75 out of 171 investigated gene sets passed the 0.005 significance threshold. Levels of gene expression were explored in three signaling pathways, Notch, Wnt, and mTOR that are known to be involved in NS cell fates determination. The transcriptional signature also deciphers the role of genes involved in epigenetic modifications. SWI/SNF DNA chromatin remodeling complex family, including SMARCC1 and SMARCE1, were found specifically up-regulated in our OBNSC but not in hENSC. Differences in gene expression profile of transcripts controlling epigenetic modifications, and signaling pathways might indicate differences in the therapeutic potential of our examined two cell populations in relation to in cell survival, proliferation, migration, and differentiation following engraftments in different CNS insults. PMID:22485144

  15. Cellular basis of neurogenesis in the brain of crayfish, Procambarus clarkii: Neurogenic complex in the olfactory midbrain from hatchlings to adults.

    PubMed

    Song, Cha-Kyong; Johnstone, Laurel M; Edwards, Donald H; Derby, Charles D; Schmidt, Manfred

    2009-07-01

    Neurogenesis in the central olfactory pathway of decapod crustaceans persists throughout life. Here we describe the structural basis of neurogenesis within the olfactory deutocerebrum of the crayfish Procambarus clarkii from hatchlings to adults. Using a proliferation marker and immunostaining, we found that throughout development each hemibrain contains a neurogenic complex consisting of five parts: two proliferation zones, each within the neuronal soma clusters containing local or projection interneurons, a tail of proliferating cells extending from each proliferation zone, and an elongated clump of cells where the two tails meet. The clump of cells comprises two subdivisions joined at a nucleus-free central area. Each subdivision consists of a dense group of clump cells with small, spindle-shaped nuclei and is connected to one of the proliferation zones by a strand of fibrous material encompassing the tail of proliferating cells extending from it. We identify one proliferating cell with a large nucleus in each subdivision as a putative neuroblast. Its daughter cells migrate through the strands to the associated proliferation zones, but in the strand leading to the soma cluster of local interneurons this is masked by local proliferation. We conclude that neurogenesis in the olfactory deutocerebrum of juvenile and adult P. clarkii is based on a few neuroblasts that are associated with unique clumps of cells likely representing stem cell niches.

  16. Expression and Role of VEGF in the Adult Retinal Pigment Epithelium

    PubMed Central

    Ford, Knatokie M.; Saint-Geniez, Magali; Walshe, Tony; Zahr, Alisar

    2011-01-01

    Purpose. Despite a lack of active angiogenesis, VEGF is expressed in nearly every adult tissue, and recent evidence suggests that VEGF may serve as a survival factor for both vascular and nonvascular tissues. VEGF blockade is a widely used treatment for neovascular diseases such as wet age-related macular degeneration (AMD). Therefore, it was sought in this study to evaluate the expression and role of endogenous VEGF in RPE. Methods. VEGF and VEGFR2 expression in the murine retina were assessed during development. Bevacizumab was used to neutralize VEGF in ARPE-19 cells, and the effects on cell survival and apical microvill were assessed by TUNEL and SEM, respectively. VEGF was systemically neutralized in vivo by adenoviral-mediated overexpression of soluble VEGFR1 (sFlt). RPE and choriocapillaris were analyzed by transmission electron microscopy (TEM). Changes in gene expression were evaluated by quantitative real-time PCR. Results. VEGF expression was detected in the developing RPE as early as embryonic day (E) 9.5, whereas VEGFR2 expression by RPE began nonuniformly between postnatal (P) day 6.5 and P8.5. VEGF neutralization in vitro led to increased apoptosis and reduced microvilli density and length. Systemic VEGF neutralization led to transient degenerative changes; RPE were vacuolated and separated from photoreceptor outer segments, and choriocapillaris fenestrations were decreased. VEGF levels were elevated in RPE of Ad-sFlt1 mice at day 4 postinfection, and there was increased expression of the neurotrophic factor CD59a at day 14. Conclusions. These results indicate that VEGF plays a critical role in survival and maintenance of RPE integrity. Potential undesired off-target effects should be considered with chronic use of anti-VEGF agents. PMID:22058334

  17. Paraneoplastic syndromes in olfactory neuroblastoma

    PubMed Central

    Gabrych, Anna; Czapiewski, Piotr; Sworczak, Krzysztof

    2015-01-01

    Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of sinonasal tract, derived from olfactory epithelium. Unilateral nasal obstruction, epistaxis, sinusitis, and headaches are common symptoms. Olfactory neuroblastoma shows neuroendocrine differentiation and similarly to other neuroendocrine tumors can produce several types of peptic substances and hormones. Excess production of these substances can be responsible for different types of endocrinological paraneoplastic syndromes (PNS). Moreover, besides endocrinological, in ONB may also occur neurological PNS, caused by immune cross-reactivity between tumor and normal host tissues in the nervous system. Paraneoplastic syndromes in ONB include: syndrome of inappropriate ADH secretion (SIADH), ectopic ACTH syndrome (EAS), humoral hypercalcemia of malignancy (HHM), hypertension due to catecholamine secretion by tumor, opsoclonus-myoclonus-ataxia (OMA) and paraneoplastic cerebellar degeneration. Paraneoplastic syndromes in ONB tend to have atypical features, therefore diagnosis may be difficult. In this review, we described initial symptoms, patterns of presentation, treatment and outcome of paraneoplastic syndromes in ONB, reported in the literature. PMID:26199564

  18. Molecular Mechanisms of Olfactory Responses to Stimulus Mixtures

    DTIC Science & Technology

    1991-02-26

    addition, the recent molecular cloning of the olfactory neuron-specific G- protein, Golf, from rat olfactory epithelium (25), has prompted a re-evaluation... molecular cloning of a G-protein that is exclusively expressed within olfactory neurons (25) prompted a re-evaluation of the molecular identities of...Fritsch, E.F. and Maniatis, T. (1989) Plasmid vectors. In Molecular Cloning : A Laboratory Manual, pp. 1.1-1.110. Cold Spring Harbor Laboratory Press, Cold

  19. Zonal organization of the mammalian main and accessory olfactory systems.

    PubMed Central

    Mori, K; von Campenhause, H; Yoshihara, Y

    2000-01-01

    Zonal organization is one of the characteristic features observed in both main and accessory olfactory systems. In the main olfactory system, most of the odorant receptors are classified into four groups according to their zonal expression patterns in the olfactory epithelium. Each group of odorant receptors is expressed by sensory neurons distributed within one of four circumscribed zones. Olfactory sensory neurons in a given zone of the epithelium project their axons to the glomeruli in a corresponding zone of the main olfactory bulb. Glomeruli in the same zone tend to represent similar odorant receptors having similar tuning specificity to odorants. Vomeronasal receptors (or pheromone receptors) are classified into two groups in the accessory olfactory system. Each group of receptors is expressed by vomeronasal sensory neurons in either the apical or basal zone of the vomeronasal epithelium. Sensory neurons in the apical zone project their axons to the rostral zone of the accessory olfactory bulb and form synaptic connections with mitral tufted cells belonging to the rostral zone. Signals originated from basal zone sensory neurons are sent to mitral tufted cells in the caudal zone of the accessory olfactory bulb. We discuss functional implications of the zonal organization in both main and accessory olfactory systems. PMID:11205342

  20. Olfactory-mediated stream-finding behavior of migratory adult sea lamprey (Petromyzon marinus)

    USGS Publications Warehouse

    Vrieze, L.A.; Bergstedt, R.A.; Sorensen, P.W.

    2011-01-01

    Stream-finding behavior of adult sea lamprey (Petromyzon marinus), an anadromous fish that relies on pheromones to locate spawning streams, was documented in the vicinity of an important spawning river in the Great Lakes. Untreated and anosmic migrating sea lampreys were implanted with acoustic transmitters and then released outside the Ocqueoc River. Lampreys swam only at night and then actively. When outside of the river plume, lampreys pursued relatively straight bearings parallel to the shoreline while making frequent vertical excursions. In contrast, when within the plume, lampreys made large turns and exhibited a weak bias towards the river mouth, which one-third of them entered. The behavior of anosmic lampreys resembled that of untreated lampreys outside of the plume, except they pursued a more northerly compass bearing. To locate streams, sea lampreys appear to employ a three-phase odor-mediated strategy that involves an initial search along shorelines while casting vertically, followed by river-water-induced turning that brings them close to the river's mouth, which they then enter using rheotaxis. This novel strategy differs from that of salmonids and appears to offer this poor swimmer adaptive flexibility and suggests ways that pheromonal odors might be used to manage this invasive species.

  1. Damage to Olfactory Progenitor Cells Is Involved in Cigarette Smoke-Induced Olfactory Dysfunction in Mice.

    PubMed

    Ueha, Rumi; Ueha, Satoshi; Kondo, Kenji; Sakamoto, Takashi; Kikuta, Shu; Kanaya, Kaori; Nishijima, Hironobu; Matsushima, Kouji; Yamasoba, Tatsuya

    2016-03-01

    Exposure to cigarette smoke is a major cause of olfactory dysfunction. However, the underlying mechanisms by which cigarette smoke interferes with the highly regenerative olfactory nerve system remain unclear. To investigate whether cigarette smoke induces olfactory dysfunction by disrupting cell proliferation and cell survival in the olfactory epithelium (OE), we developed a mouse model of smoking that involved intranasal administration of a cigarette smoke solution (CSS). Immunohistological analyses and behavioral testing showed that CSS administration during a period of 24 days reduced the number of olfactory marker protein-positive mature olfactory receptor neurons (ORNs) in the OE and induced olfactory dysfunction. These changes coincided with a reduction in the number of SOX2(+) ORN progenitors and Ki-67(+) proliferating cells in the basal layer of the OE, an increase in the number of caspase-3(+) apoptotic cells, and an increase in the expression of mRNA for the inflammatory cytokines IL-1β and IL-6. Notably, the proliferating ORN progenitor population recovered after cessation of treatment with CSS, resulting in the subsequent restoration of mature ORN numbers and olfaction. These results suggest that SOX2(+) ORN progenitors are targets of CSS-induced impairment of the OE, and that by damaging the ORN progenitor population and increasing ORN death, CSS exposure eventually overwhelms the regenerative capacity of the epithelium, resulting in reduced numbers of mature ORNs and olfactory dysfunction.

  2. Anatomical specializations for enhanced olfactory sensitivity in kiwi, Apteryx mantelli.

    PubMed

    Corfield, Jeremy R; Eisthen, Heather L; Iwaniuk, Andrew N; Parsons, Stuart

    2014-01-01

    The ability to function in a nocturnal and ground-dwelling niche requires a unique set of sensory specializations. The New Zealand kiwi has shifted away from vision, instead relying on auditory and tactile stimuli to function in its environment and locate prey. Behavioral evidence suggests that kiwi also rely on their sense of smell, using olfactory cues in foraging and possibly also in communication and social interactions. Anatomical studies appear to support these observations: the olfactory bulbs and tubercles have been suggested to be large in the kiwi relative to other birds, although the extent of this enlargement is poorly understood. In this study, we examine the size of the olfactory bulbs in kiwi and compare them with 55 other bird species, including emus, ostriches, rheas, tinamous, and 2 extinct species of moa (Dinornithiformes). We also examine the cytoarchitecture of the olfactory bulbs and olfactory epithelium to determine if any neural specializations beyond size are present that would increase olfactory acuity. Kiwi were a clear outlier in our analysis, with olfactory bulbs that are proportionately larger than those of any other bird in this study. Emus, close relatives of the kiwi, also had a relative enlargement of the olfactory bulbs, possibly supporting a phylogenetic link to well-developed olfaction. The olfactory bulbs in kiwi are almost in direct contact with the olfactory epithelium, which is indeed well developed and complex, with olfactory receptor cells occupying a large percentage of the epithelium. The anatomy of the kiwi olfactory system supports an enhancement for olfactory sensitivities, which is undoubtedly associated with their unique nocturnal niche.

  3. Thermally reduced graphene is a permissive material for neurons and astrocytes and de novo neurogenesis in the adult olfactory bulb in vivo.

    PubMed

    Defteralı, Çağla; Verdejo, Raquel; Peponi, Laura; Martín, Eduardo D; Martínez-Murillo, Ricardo; López-Manchado, Miguel Ángel; Vicario-Abejón, Carlos

    2016-03-01

    Graphene and graphene-based nanomaterials (GBNs) are being investigated as potential substrates for the growth of neural stem cells (NSCs), neurons and glia in cell culture models. In contrast, reports testing the effects of graphene directly with adult neural cells in vivo are missing. Here we studied the biocompatibility of thermally reduced graphene (TRG) with neurons and glia, as well as with the generation of new neurons in the adult brain in vivo. TRG injected in the brain together with a retroviral vector expressing GFP to label dividing progenitor cells in the core of the adult olfactory bulb (OB) did not alter de novo neurogenesis, neuronal and astrocyte survival nor did it produce a microglial response. These findings indicate that TRG may be a biocompatible material with neuronal and glial cells in vivo and support its use in studies of brain repair and function.

  4. Olfactory toxicity in fishes.

    PubMed

    Tierney, Keith B; Baldwin, David H; Hara, Toshiaki J; Ross, Peter S; Scholz, Nathaniel L; Kennedy, Christopher J

    2010-01-21

    Olfaction conveys critical environmental information to fishes, enabling activities such as mating, locating food, discriminating kin, avoiding predators and homing. All of these behaviors can be impaired or lost as a result of exposure to toxic contaminants in surface waters. Historically, teleost olfaction studies have focused on behavioral responses to anthropogenic contaminants (e.g., avoidance). More recently, there has been a shift towards understanding the underlying mechanisms and functional significance of contaminant-mediated changes in fish olfaction. This includes a consideration of how contaminants affect the olfactory nervous system and, by extension, the downstream physiological and behavioral processes that together comprise a normal response to naturally occurring stimuli (e.g., reproductive priming or releasing pheromones). Numerous studies spanning several species have shown that ecologically relevant exposures to common pollutants such as metals and pesticides can interfere with fish olfaction and disrupt life history processes that determine individual survival and reproductive success. This represents one of the pathways by which toxic chemicals in aquatic habitats may increasingly contribute to the decline and at-risk status of many commercially and ecologically important fish stocks. Despite our emerging understanding of the threats that pollution poses for chemical communication in aquatic communities, many research challenges remain. These include: (1) the determination of specific mechanisms of toxicity in the fish olfactory sensory epithelium; (2) an understanding of the impacts of complex chemical mixtures; (3) the capacity to assess olfactory toxicity in fish in situ; (4) the impacts of toxins on olfactory-mediated behaviors that are still poorly understood for many fish species; and (5) the connections between sublethal effects on individual fish and the long-term viability of wild populations. This review summarizes and integrates

  5. Olfactory and solitary chemosensory cells: two different chemosensory systems in the nasal cavity of the American alligator, Alligator mississippiensis

    PubMed Central

    Hansen, Anne

    2007-01-01

    Background The nasal cavity of all vertebrates houses multiple chemosensors, either innervated by the Ist (olfactory) or the Vth (trigeminal) cranial nerve. Various types of receptor cells are present, either segregated in different compartments (e.g. in rodents) or mingled in one epithelium (e.g. fish). In addition, solitary chemosensory cells have been reported for several species. Alligators which seek their prey both above and under water have only one nasal compartment. Information about their olfactory epithelium is limited. Since alligators seem to detect both volatile and water-soluble odour cues, I tested whether different sensory cell types are present in the olfactory epithelium. Results Electron microscopy and immunocytochemistry were used to examine the sensory epithelium of the nasal cavity of the American alligator. Almost the entire nasal cavity is lined with olfactory (sensory) epithelium. Two types of olfactory sensory neurons are present. Both types bear cilia as well as microvilli at their apical endings and express the typical markers for olfactory neurons. The density of these olfactory neurons varies along the nasal cavity. In addition, solitary chemosensory cells innervated by trigeminal nerve fibres, are intermingled with olfactory sensory neurons. Solitary chemosensory cells express components of the PLC-transduction cascade found in solitary chemosensory cells in rodents. Conclusion The nasal cavity of the American alligator contains two different chemosensory systems incorporated in the same sensory epithelium: the olfactory system proper and solitary chemosensory cells. The olfactory system contains two morphological distinct types of ciliated olfactory receptor neurons. PMID:17683564

  6. Gyrodactylus salmonis infection impairs the olfactory system of rainbow trout.

    PubMed

    Lari, E; Pyle, G G

    2017-01-20

    Monogenean worms are ectoparasites that are known to be infectious to a wide variety of fish. Few species of monogenean parasites have been reported in the olfactory chamber of fish in current peer-reviewed literature. However, the impacts of these parasites on the olfactory system are not well understood. In this study, the effects of Gyrodactylus salmonis on the olfactory system structure and performance were investigated in rainbow trout (Oncorhynchus mykiss). The olfactory performance of the infected fish was examined using an electro-olfactography (EOG) technique, while the ultrastructure of the olfactory rosette was studied using scanning electron microscopy (SEM) and light microscopy (LM). The infected rainbow trout displayed reduced responses to two standard olfactory cues (L-alanine and TCA). The SEM micrographs revealed that many regions of the olfactory epithelium in the infected fish were heavily pitted and the LM examination of the olfactory epithelium showed local proliferation of mucous cells in the sensory regions as compared to the control group. The results of this study demonstrated that G. salmonis causes physical damage to the olfactory system of fish that lead to olfactory impairment.

  7. Expression of Coxsackie-Adenovirus receptor (CAR) in the developing mouse olfactory system.

    PubMed

    Venkatraman, Giri; Behrens, Maik; Pyrski, Martina; Margolis, Frank L

    2005-09-01

    Interest in manipulating gene expression in olfactory sensory neurons (OSNs) has led to the use of adenoviruses (AdV) as gene delivery vectors. OSNs are the first order neurons in the olfactory system and the initial site of odor detection. They are highly susceptible to adenovirus infection although the mechanism is poorly understood. The Coxsackie-Adenovirus receptor (CAR) and members of the integrin family have been implicated in the process of AdV infection in various systems. Multiple serotypes of AdV efficiently bind to the CAR, leading to entry and infection of the host cell by a mechanism that can also involve integrins. Cell lines that do not express CAR are relatively resistant, but not completely immune to AdV infection, suggesting that other mechanisms participate in mediating AdV attachment and entry. Using in situ hybridization and western blot analyses, we show that OSNs and olfactory bulbs (OB) of mice express abundant CAR mRNA at embryonic and neonatal stages, with progressive diminution during postnatal development. By contrast to the olfactory epithelium (OE), CAR mRNA is still present in the adult mouse OB. Furthermore, despite a similar postnatal decline, CAR protein expression in the OE and OB of mice continues into adulthood. Our results suggest that the robust AdV infection observed in the postnatal olfactory system is mediated by CAR and that expression of even small amounts of CAR protein as seen in the adult rodent, permits efficient AdV infection and entry. CAR is an immunoglobulin domain-containing protein that bears homology to cell-adhesion molecules suggesting the possibility that it may participate in organization of the developing olfactory system.

  8. Dietary sodium protects fish against copper-induced olfactory impairment.

    PubMed

    Azizishirazi, Ali; Dew, William A; Bougas, Berenice; Bernatchez, Louis; Pyle, Greg G

    2015-04-01

    Exposure to low concentrations of copper impairs olfaction in fish. To determine the transcriptional changes in the olfactory epithelium induced by copper exposure, wild yellow perch (Perca flavescens) were exposed to 20 μg/L of copper for 3 and 24h. A novel yellow perch microarray with 1000 candidate genes was used to measure differential gene transcription in the olfactory epithelium. While three hours of exposure to copper changed the transcription of only one gene, the transcriptions of 70 genes were changed after 24h of exposure to copper. Real-time PCR was utilized to determine the effect of exposure duration on two specific genes of interest, two sub-units of Na/K-ATPase. At 24 and 48 h, Na/K-ATPase transcription was down-regulated by copper at olfactory rosettes. As copper-induced impairment of Na/K-ATPase activity in gills can be ameliorated by increased dietary sodium, rainbow trout (Oncorhynchus mykiss) were used to determine if elevated dietary sodium was also protective against copper-induced olfactory impairment. Measurement of the olfactory response of rainbow trout using electro-olfactography demonstrated that sodium was protective of copper-induced olfactory dysfunction. This work demonstrates that the transcriptions of both subunits of Na/K-ATPase in the olfactory epithelium of fish are affected by Cu exposure, and that dietary Na protects against Cu-induced olfactory dysfunction.

  9. OTX1 and OTX2 as Possible Molecular Markers of Sinonasal Carcinomas and Olfactory Neuroblastomas

    PubMed Central

    Pirrone, Cristina; Chiaravalli, Anna M.; Marando, Alessandro; Conti, Andrea; Rainero, Alessia; Pistochini, Andrea; Curto, Francesco Lo; Pasquali, Francesco; Castelnuovo, Paolo; Capella, Carlo; Porta, Giovanni

    2017-01-01

    OTX Homeobox genes are involved in embryonic morphogenesis and in the development of olfactory epithelium in adult. Mutations occurring in the OTX genes are reported to be associated to tumorigenisis in human. No reports correlate the expression of OTX genes and neoplasms of the nasal cavity. Thus, through immunohistochemical and Real-time PCR analysis we investigated OTX1 and OTX2 expression in the more frequent types of nasal and sinonasal tumours. Variable expression of both genes were found in normal sinonasal mucosa and in tumours. Interestingly, no expression of both OTX genes were detected in sinonasal intestinal-type adenocarcinomas; only OTX1 was found in non-intestinal-type adenocarcinomas and OTX2 was selectively expressed in olfactory neuroblastomas. In conclusion, OTX1 and OTX2 genes might have a role in the pathogenesis of different types of sinonasal neoplasms. PMID:28348423

  10. Diverse systems for pheromone perception: multiple receptor families in two olfactory systems.

    PubMed

    Hagino-Yamagishi, Kimiko

    2008-12-01

    Traditionally, the olfactory epithelium is considered to recognize conventional odors, while the vomeronasal organ detects pheromones. However, recent advances suggest that vertebrate pheromones can also be detected by the olfactory epithelium. In the vomeronasal organ and the olfactory epithelium, structurally distinct multiple receptor families are expressed. In rodents, two of these receptor families, V1R and V2R, are expressed specifically in the vomeronasal organ and detect pheromones and pheromone candidates. A newly isolated trace amine-associated receptor detects some of the putative pheromones in the mouse olfactory epithelium. In addition, distinct second-messenger pathways and neural circuits are used for pheromone perception mediated by each receptor family. Furthermore, the function of these receptor families in these olfactory organs appears to differ among various vertebrate species. The systems for pheromone perception in vertebrates are far more complex than previously predicted.

  11. A multisensory network for olfactory processing

    PubMed Central

    Maier, Joost X.; Blankenship, Meredith L.; Li, Jennifer X.; Katz, Donald B.

    2015-01-01

    Summary Primary gustatory cortex (GC) is connected (both mono- and poly-synaptically) to primary olfactory (piriform) cortex (PC)—connections that might be hypothesized to underlie the construction of a “flavor” percept when both gustatory and olfactory stimuli are present. Here, we use multi-site electrophysiology and optical inhibition of GC neurons (GCx, produced via infection with ArchT) to demonstrate that, indeed, during gustatory stimulation, taste-selective information is transmitted from GC to PC. We go on to show that these connections impact olfactory processing even in the absence of gustatory stimulation: GCx alters PC responses to olfactory stimuli presented alone, enhancing some and eliminating others, despite leaving the path from nasal epithelium to PC intact. Finally, we show the functional importance of this latter phenomenon, demonstrating that GCx renders rats unable to properly recognize odor stimuli. This sequence of findings suggests that sensory processing may be more intrinsically integrative than previously thought. PMID:26441351

  12. Development of a glial network in the olfactory nerve: role of calcium and neuronal activity.

    PubMed

    Koussa, Mounir A; Tolbert, Leslie P; Oland, Lynne A

    2010-11-01

    In adult olfactory nerves of mammals and moths, a network of glial cells ensheathes small bundles of olfactory receptor axons. In the developing antennal nerve (AN) of the moth Manduca sexta, the axons of olfactory receptor neurons (ORNs) migrate from the olfactory sensory epithelium toward the antennal lobe. Here we explore developmental interactions between ORN axons and AN glial cells. During early stages in AN glial-cell migration, glial cells are highly dye coupled, dividing glia are readily found in the nerve and AN glial cells label strongly for glutamine synthetase. By the end of this period, dye-coupling is rare, glial proliferation has ceased, glutamine synthetase labeling is absent, and glial processes have begun to extend to enwrap bundles of axons, a process that continues throughout the remainder of metamorphic development. Whole-cell and perforated-patch recordings in vivo from AN glia at different stages of network formation revealed two potassium currents and an R-like calcium current. Chronic in vivo exposure to the R-type channel blocker SNX-482 halted or greatly reduced AN glial migration. Chronically blocking spontaneous Na-dependent activity by injection of tetrodotoxin reduced the glial calcium current implicating an activity-dependent interaction between ORNs and glial cells in the development of glial calcium currents.

  13. Investigation of olfactory function in a Panx1 knock out mouse model

    PubMed Central

    Kurtenbach, Stefan; Whyte-Fagundes, Paige; Gelis, Lian; Kurtenbach, Sarah; Brazil, Émerson; Zoidl, Christiane; Hatt, Hanns; Shestopalov, Valery I.; Zoidl, Georg

    2014-01-01

    Pannexin 1 (Panx1), the most extensively investigated member of a channel-forming protein family, is able to form pores conducting molecules up to 1.5 kDa, like ATP, upon activation. In the olfactory epithelium (OE), ATP modulates olfactory responsiveness and plays a role in proliferation and differentiation of olfactory sensory neurons (OSNs). This process continuously takes place in the OE, as neurons are replaced throughout the whole lifespan. The recent discovery of Panx1 expression in the OE raises the question whether Panx1 mediates ATP release responsible for modulating chemosensory function. In this study, we analyzed pannexin expression in the OE and a possible role of Panx1 in olfactory function using a Panx1−/− mouse line with a global ablation of Panx1. This mouse model has been previously used to investigate Panx1 functions in the retina and adult hippocampus. Here, qPCR, in-situ hybridization, and immunohistochemistry (IHC) demonstrated that Panx1 is expressed in axon bundles deriving from sensory neurons of the OE. The localization, distribution, and expression of major olfactory signal transduction proteins were not significantly altered in Panx1−/− mice. Further, functional analysis of Panx1−/− animals does not reveal any major impairment in odor perception, indicated by electroolfactogram (EOG) measurements and behavioral testing. However, ATP release evoked by potassium gluconate application was reduced in Panx1−/− mice. This result is consistent with previous reports on ATP release in isolated erythrocytes and spinal or lumbar cord preparations from Panx1−/− mice, suggesting that Panx1 is one of several alternative pathways to release ATP in the olfactory system. PMID:25309319

  14. Phylogenic Studies on the Olfactory System in Vertebrates

    PubMed Central

    TANIGUCHI, Kazuyuki; TANIGUCHI, Kazumi

    2014-01-01

    ABSTRACT The olfactory receptor organs and their primary centers are classified into several types. The receptor organs are divided into fish-type olfactory epithelium (OE), mammal-type OE, middle chamber epithelium (MCE), lower chamber epithelium (LCE), recess epithelium, septal olfactory organ of Masera (SO), mammal-type vomeronasal organ (VNO) and snake-type VNO. The fish-type OE is observed in flatfish and lungfish, while the mammal-type OE is observed in amphibians, reptiles, birds and mammals. The MCE and LCE are unique to Xenopus and turtles, respectively. The recess epithelium is unique to lungfish. The SO is observed only in mammals. The mammal-type VNO is widely observed in amphibians, lizards and mammals, while the snake-type VNO is unique to snakes. The VNO itself is absent in turtles and birds. The mammal-type OE, MCE, LCE and recess epithelium seem to be descendants of the fish-type OE that is derived from the putative primitive OE. The VNO may be derived from the recess epithelium or fish-type OE and differentiate into the mammal-type VNO and snake-type VNO. The primary olfactory centers are divided into mammal-type main olfactory bulbs (MOB), fish-type MOB and mammal-type accessory olfactory bulbs (AOB). The mammal-type MOB first appears in amphibians and succeeds to reptiles, birds and mammals. The fish-type MOB, which is unique to fish, may be the ancestor of the mammal-type MOB. The mammal-type AOB is observed in amphibians, lizards, snakes and mammals and may be the remnant of the fish-type MOB. PMID:24531771

  15. Anatomy and forebrain projections of the olfactory and vomeronasal organs in axolotls (Ambystoma mexicanum).

    PubMed

    Eisthen, H L; Sengelaub, D R; Schroeder, D M; Alberts, J R

    1994-01-01

    We examined the anatomy of the nasal cavity and forebrain in the axolotl (Ambystoma mexicanum) to determine whether the olfactory and vomeronasal systems are present in this neotenic aquatic salamander. The current study was motivated by two considerations: (a) little is known of the anatomy of the vomeronasal system in aquatic vertebrates, and (b) the presence of both olfactory and vomeronasal systems in larval amphibians has broad implications for the evaluation of these systems in vertebrates. From cresyl-violet-stained sections of snouts we determined that the nasal cavity of axolotls is much like that of terrestrial salamanders. The main chamber of the nasal cavity contains an olfactory epithelium, which is confined to grooves between longitudinal ridges of connective tissue covered in a nonsensory epithelium which lacks goblet cells. Using transmission electron microscopy, we found morphologically distinct olfactory receptor cells: many receptor cells terminate in microvillar dendrites, and fewer terminate in motile cilia with the 9 + 2 microtubule array typical of vertebrate olfactory receptor cells. The ciliated and microvillar cells occur in clusters with little intermingling. Horseradish peroxidase labeling revealed that axons of the olfactory receptor cells terminate in large glomeruli in the main olfactory bulb at the rostral end of the telencephalon. Lateral to the main chamber of the nasal cavity is a diverticulum that is entirely lined with a vomeronasal epithelium containing basal cells, microvillar receptor cells, sustentacular cells that lack specialized processes on the apical surface, and large ciliated cells that may function to move fluid across the vomeronasal epithelium. Unlike the olfactory epithelium, the vomeronasal epithelium lacks Bowman's glands. Using horseradish peroxidase, we determined that the axons of the vomeronasal receptor cells project to the accessory olfactory bulb, a distinct structure dorsal and caudal to the main

  16. Pax6 Is Essential for the Maintenance and Multi-Lineage Differentiation of Neural Stem Cells, and for Neuronal Incorporation into the Adult Olfactory Bulb

    PubMed Central

    Curto, Gloria G.; Nieto-Estévez, Vanesa; Hurtado-Chong, Anahí; Valero, Jorge; Gómez, Carmela; Alonso, José R.; Weruaga, Eduardo

    2014-01-01

    The paired type homeobox 6 (Pax6) transcription factor (TF) regulates multiple aspects of neural stem cell (NSC) and neuron development in the embryonic central nervous system. However, less is known about the role of Pax6 in the maintenance and differentiation of adult NSCs and in adult neurogenesis. Using the +/SeyDey mouse, we have analyzed how Pax6 heterozygosis influences the self-renewal and proliferation of adult olfactory bulb stem cells (aOBSCs). In addition, we assessed its influence on neural differentiation, neuronal incorporation, and cell death in the adult OB, both in vivo and in vitro. Our results indicate that the Pax6 mutation alters Nestin+-cell proliferation in vivo, as well as self-renewal, proliferation, and survival of aOBSCs in vitro although a subpopulation of +/SeyDey progenitors is able to expand partially similar to wild-type progenitors. This mutation also impairs aOBSC differentiation into neurons and oligodendrocytes, whereas it increases cell death while preserving astrocyte survival and differentiation. Furthermore, Pax6 heterozygosis causes a reduction in the variety of neurochemical interneuron subtypes generated from aOBSCs in vitro and in the incorporation of newly generated neurons into the OB in vivo. Our findings support an important role of Pax6 in the maintenance of aOBSCs by regulating cell death, self-renewal, and cell fate, as well as in neuronal incorporation into the adult OB. They also suggest that deregulation of the cell cycle machinery and TF expression in aOBSCs which are deficient in Pax6 may be at the origin of the phenotypes observed in this adult NSC population. PMID:25117830

  17. Establishment of a novel lingual organoid culture system: generation of organoids having mature keratinized epithelium from adult epithelial stem cells.

    PubMed

    Hisha, Hiroko; Tanaka, Toshihiro; Kanno, Shohei; Tokuyama, Yoko; Komai, Yoshihiro; Ohe, Shuichi; Yanai, Hirotsugu; Omachi, Taichi; Ueno, Hiroo

    2013-11-15

    Despite the strong need for the establishment of a lingual epithelial cell culture system, a simple and convenient culture method has not yet been established. Here, we report the establishment of a novel lingual epithelium organoid culture system using a three-dimensional matrix and growth factors. Histological analyses showed that the generated organoids had both a stratified squamous epithelial cell layer and a stratum corneum. Very recently, we showed via a multicolor lineage tracing method that Bmi1-positive stem cells exist at the base of the epithelial basal layer in the interpapillary pit. Using our new culture system, we found that organoids could be generated by single Bmi1-positive stem cells and that in the established organoids, multiple Bmi1-positive stem cells were generated at the outermost layer. Moreover, we observed that organoids harvested at an early point in culture could be engrafted and maturate in the tongue of recipient mice and that the organoids generated from carcinogen-treated mice had an abnormal morphology. Thus, this culture system presents valuable settings for studying not only the regulatory mechanisms of lingual epithelium but also lingual regeneration and carcinogenesis.

  18. Establishment of a Novel Lingual Organoid Culture System: Generation of Organoids Having Mature Keratinized Epithelium from Adult Epithelial Stem Cells

    NASA Astrophysics Data System (ADS)

    Hisha, Hiroko; Tanaka, Toshihiro; Kanno, Shohei; Tokuyama, Yoko; Komai, Yoshihiro; Ohe, Shuichi; Yanai, Hirotsugu; Omachi, Taichi; Ueno, Hiroo

    2013-11-01

    Despite the strong need for the establishment of a lingual epithelial cell culture system, a simple and convenient culture method has not yet been established. Here, we report the establishment of a novel lingual epithelium organoid culture system using a three-dimensional matrix and growth factors. Histological analyses showed that the generated organoids had both a stratified squamous epithelial cell layer and a stratum corneum. Very recently, we showed via a multicolor lineage tracing method that Bmi1-positive stem cells exist at the base of the epithelial basal layer in the interpapillary pit. Using our new culture system, we found that organoids could be generated by single Bmi1-positive stem cells and that in the established organoids, multiple Bmi1-positive stem cells were generated at the outermost layer. Moreover, we observed that organoids harvested at an early point in culture could be engrafted and maturate in the tongue of recipient mice and that the organoids generated from carcinogen-treated mice had an abnormal morphology. Thus, this culture system presents valuable settings for studying not only the regulatory mechanisms of lingual epithelium but also lingual regeneration and carcinogenesis.

  19. Olfactory deposition of inhaled nanoparticles in humans

    PubMed Central

    Garcia, Guilherme J. M.; Schroeter, Jeffry D.; Kimbell, Julia S.

    2016-01-01

    Context Inhaled nanoparticles can migrate to the brain via the olfactory bulb, as demonstrated in experiments in several animal species. This route of exposure may be the mechanism behind the correlation between air pollution and human neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Objectives This manuscript aims to (1) estimate the dose of inhaled nanoparticles that deposit in the human olfactory epithelium during nasal breathing at rest and (2) compare the olfactory dose in humans with our earlier dose estimates for rats. Materials and methods An anatomically-accurate model of the human nasal cavity was developed based on computed tomography scans. The deposition of 1–100 nm particles in the whole nasal cavity and its olfactory region were estimated via computational fluid dynamics (CFD) simulations. Our CFD methods were validated by comparing our numerical predictions for whole-nose deposition with experimental data and previous CFD studies in the literature. Results In humans, olfactory dose of inhaled nanoparticles is highest for 1–2 nm particles with approximately 1% of inhaled particles depositing in the olfactory region. As particle size grows to 100 nm, olfactory deposition decreases to 0.01% of inhaled particles. Discussion and conclusion Our results suggest that the percentage of inhaled particles that deposit in the olfactory region is lower in humans than in rats. However, olfactory dose per unit surface area is estimated to be higher in humans due to their larger minute volume. These dose estimates are important for risk assessment and dose-response studies investigating the neurotoxicity of inhaled nanoparticles. PMID:26194036

  20. Making scent of the presence and local translation of odorant receptor mRNAs in olfactory axons.

    PubMed

    Dubacq, Caroline; Fouquet, Coralie; Trembleau, Alain

    2014-03-01

    Rodents contain in their genome more than 1000 functional odorant receptor genes, which are specifically expressed by the olfactory sensory neurons projecting from the olfactory epithelium to the olfactory bulb. Strong evidence for the presence and local translation of odorant receptor mRNAs in the axon of olfactory sensory neurons was obtained, but no function has been assigned to these axonal mRNAs yet. The aim of this review is to discuss the evidence for the presence and local translation of odorant receptor mRNAs in olfactory sensory axons, and to speculate on their possible function in the wiring of the mouse olfactory sensory projections.

  1. Nested expression domains for odorant receptors in zebrafish olfactory epithelium

    PubMed Central

    Weth, Franco; Nadler, Walter; Korsching, Sigrun

    1996-01-01

    The mapping of high-dimensional olfactory stimuli onto the two-dimensional surface of the nasal sensory epithelium constitutes the first step in the neuronal encoding of olfactory input. We have used zebrafish as a model system to analyze the spatial distribution of odorant receptor molecules in the olfactory epithelium by quantitative in situ hybridization. To this end, we have cloned 10 very divergent zebrafish odorant receptor molecules by PCR. Individual genes are expressed in sparse olfactory receptor neurons. Analysis of the position of labeled cells in a simplified coordinate system revealed three concentric, albeit overlapping, expression domains for the four odorant receptors analyzed in detail. Such regionalized expression should result in a corresponding segregation of functional response properties. This might represent the first step of spatial encoding of olfactory input or be essential for the development of the olfactory system. PMID:8917589

  2. Direct transport of inhaled xylene and its metabolites from the olfactory mucosa to the glomeruli of the olfactory bulbs

    SciTech Connect

    Lewis, J.L.; Dahl, A.R.; Kracko, D.A.

    1994-11-01

    The olfactory epithelium is a unique tissue in that single receptor neurons have dendrites in contact with the external environment at the nasal airway, and axon terminals that penetrate the cribriform plate and synapse in the olfactory bulb. The Central Nervous System (CNS) is protected from systematically circulating toxicants by a blood-brain barrier primarily composed of tight junctions between endothelial cells in cerebral vessels and a high metabolic capacity within these cells. No such barrier has yet been defined to protect the CNS from inhaled toxicants. Because all inhalants do not seem to access the CNS directly, a nose-brain barrier seems plausible. The purpose of the work described here is to determine whether or not a nose-brain barrier exists and to define its components. Although such a barrier is likely to be multi-faceted, the present work focuses only on the importance of gross histologic and metabolic characteristics of the olfactory epithelium in olfactory transport.

  3. Differences between the neurogenic and proliferative abilities of Müller glia with stem cell characteristics and the ciliary epithelium from the adult human eye.

    PubMed

    Bhatia, Bhairavi; Jayaram, Hari; Singhal, Shweta; Jones, Megan F; Limb, G Astrid

    2011-12-01

    Much controversy has arisen on the nature and sources of stem cells in the adult human retina. Whilst ciliary epithelium has been thought to constitute a source of neural stem cells, a population of Müller glia in the neural retina has also been shown to exhibit neurogenic characteristics. This study aimed to compare the neurogenic and proliferative abilities between these two major cell populations. It also examined whether differences exist between the pigmented and non-pigmented ciliary epithelium (CE) from the adult human eye. On this basis, Müller glia with stem cell characteristics and pigmented and non-pigmented CE were isolated from human neural retina and ciliary epithelium respectively. Expression of glial, epithelial and neural progenitor markers was examined in these cells following culture under adherent and non-adherent conditions and treatments to induce neural differentiation. Unlike pigmented CE which did not proliferate, non-pigmented CE cells exhibited limited proliferation in vitro, unless epidermal growth factor (EGF) was present in the culture medium to prolong their survival. In contrast, Müller glial stem cells (MSC) cultured as adherent monolayers reached confluence within a few weeks and continued to proliferative indefinitely in the absence of EGF. Both MSC and non-pigmented CE expressed markers of neural progenitors, including SOX2, PAX6, CHX10 and NOTCH. Nestin, a neural stem cell marker, was only expressed by MSC. Non-pigmented CE displayed epithelial morphology, limited photoreceptor gene expression and stained strongly for pigmented epithelial markers upon culture with neural differentiation factors. In contrast, MSC adopted neural morphology and expressed markers of retinal ganglion cells and photoreceptors when cultured under similar conditions. This study provides the first demonstration that pigmented CE possess different proliferative abilities from non-pigmented CE. It also showed that although non-pigmented CE express genes

  4. Olfactory neuroblastoma

    SciTech Connect

    O'Connor, T.A.; McLean, P.; Juillard, G.J.; Parker, R.G.

    1989-06-15

    Fifteen patients with olfactory neuroblastoma were treated during the 17-year period of 1969 to 1986. Data was analyzed with respect to age at presentation, sex, presenting signs and symptoms, stage, and results of treatment. Age ranged from 4 to 67 years with the median age being 27 years. Median follow-up was 8 years. Local control was achieved in nine of nine patients or 100% with successful surgical resection, i.e., minimal residual disease, followed by postoperative radiation therapy (45 to 65 Gy) was employed. There were no distant failures when the primary site was controlled. Regional lymph node metastases were infrequent: only 13% (two of 15 patients) presented with positive nodes. Three of four patients treated initially with surgery alone had a local recurrence, two of which were successfully salvaged by combined therapy. There were four patients treated with radiation therapy alone: three had persistent disease after radiation therapy, and one patient was controlled with 65 Gy. Olfactory neuroblastoma has a propensity to recur locally when treated with surgery alone. The authors' experience suggests excellent local control can be achieved with surgery immediately followed by radiation therapy. Thus the authors recommend planned combined treatment for all resectable lesions.

  5. Morphological and electrophysiological examination of olfactory sensory neurons during the early developmental prolarval stage of the sea lamprey Petromyzon marinus L

    USGS Publications Warehouse

    Zielinski, B.S.; Fredricks, Keith; McDonald, R.; Zaidi, A.U.

    2005-01-01

    This study examined olfactory sensory neuron morphology and physiological responsiveness in newly hatched sea lamprey, Petromyzon marinus L. These prolarvae hatch shortly after neural tube formation, and stay within nests for approximately 18 days, before moving downstream to silty areas where they burrow, feed and pass to the larval stage. To explore the possibility that the olfactory system is functioning during this prolarval stage, morphological and physiological development of olfactory sensory neurons was examined. The nasal cavity contained an olfactory epithelium with ciliated olfactory sensory neurons. Axons formed aggregates in the basal portion of the olfactory epithelium and spanned the narrow distance between the olfactory epithelium and the brain. The presence of asymmetric synapses with agranular vesicles within fibers in the brain, adjacent to the olfactory epithelium suggests that there was synaptic connectivity between olfactory sensory axons and the brain. Neural recordings from the surface of the olfactory epithelium showed responses following the application of L-arginine, taurocholic acid, petromyzonol sulfate (a lamprey migratory pheromone), and water conditioned by conspecifics. These results suggest that lampreys may respond to olfactory sensory input during the prolarval stage. ?? 2006 Springer Science + Business Media, LLC.

  6. Microanatomy and surgical relevance of the olfactory cistern.

    PubMed

    Wang, Shou-Sen; Zheng, He-Ping; Zhang, Xiang; Zhang, Fa-Hui; Jing, Jun-Jie; Wang, Ru-Mi

    2008-01-01

    All surgical approaches to the anterior skull base involve the olfactory cistern and have the risk of damaging the olfactory nerve. The purpose of this study was to describe the microanatomical features of the olfactory cistern and discuss its surgical relevance. In this study, the olfactory cisterns of 15 formalin-fixed adult cadaveric heads were dissected using a surgical microscope. The results showed that the olfactory cistern was situated in the superficial part of the olfactory sulcus, which separated the gyrus retus from the orbital gyrus. In coronal section, the cistern was triangular in shape; its anterior part enveloped the olfactory bulbs and was high and broad; its posterior part was medial-superior to internal carotid artery and was also much broader. There were one or several openings in the inferior wall of the posterior part in 53.4% of the cisterns. The olfactory cistern communicated with the surrounding subarachnoind cisterns through these openings. The middle part of the olfactory cistern gradually narrowed down posteriorly. Most cisterns were spacious with a few fibrous trabeculas and bands between the olfactory nerves and cistern walls. However 23% of the cisterns were narrow with the cistern walls tightly encasing the olfactory nerve. There were two or three of arterial loops in each olfactory sulcus, from which long, fine olfactory arteries originated. The olfactory arteries coursed along the olfactory nerve and gave off many terminal branches to provide the main blood supply to the olfactory nerve in most cisterns, but the blood supply was in segmental style in a few cisterns. Moreover, the veins of the cistern appeared to be more segmental than the olfactory arteries in most cisterns. These results suggested that most olfactory cisterns are spacious with relatively independent blood supply, and it is reasonable to separate the olfactory tract with its independent blood supply from the frontal lobe by 1-2 cm in the subfrontal approach, the

  7. Role of Rb during Neurogenesis and Axonal Guidance in the Developing Olfactory System.

    PubMed

    Jaafar, Carine; Omais, Saad; Al Lafi, Sawsan; El Jamal, Nadim; Noubani, Mohammad; Skaf, Larissa; Ghanem, Noël

    2016-01-01

    The Retinoblastoma protein, Rb, was shown to regulate distinct aspects of neurogenesis in the embryonic and adult brain besides its primary role in cell cycle control. It is still unknown, however, whether Rb is required for tissue morphogenesis and the establishment of synaptic connections between adjacent tissues during development. We have investigated here the role of Rb during development of the olfactory system (OS), which heavily relies on reciprocal interactions between the olfactory epithelium (OE) and the olfactory bulb (OB). We show that mice carrying a telencephalic-specific deletion of Rb display several neurogenic defects in the OS during late development. In the OE, loss of Rb leads to ectopic proliferation of late-born progenitors (Tuj-1+), abnormal radial migration and terminal maturation of olfactory sensory neurons (OSNs). In the OB, deletion of Rb causes severe lamination defects with loss of clear boundaries between distinct layers. Importantly, starting around E15.5 when OB glomerulogenesis is initiated, many OSNs axons that project along the olfactory nerve layer (ONL) fail to properly innervate the nascent bulb, thus resulting in partial loss of connectivity between OE-OB and gradual neuronal degeneration in both tissues peaking at birth. This deficiency correlates with deregulated expressions of two key chemo-repellant molecules, Robo2/Slit1 and Nrp2/Sema3F that control the formation of dorsal-ventral topographic map of OSNs connections with OB glomeruli. This study highlights a critical requirement for Rb during neurogenesis and the establishment of proper synaptic connections inside the OS during development.

  8. Role of Rb during Neurogenesis and Axonal Guidance in the Developing Olfactory System

    PubMed Central

    Jaafar, Carine; Omais, Saad; Al Lafi, Sawsan; El Jamal, Nadim; Noubani, Mohammad; Skaf, Larissa; Ghanem, Noël

    2016-01-01

    The Retinoblastoma protein, Rb, was shown to regulate distinct aspects of neurogenesis in the embryonic and adult brain besides its primary role in cell cycle control. It is still unknown, however, whether Rb is required for tissue morphogenesis and the establishment of synaptic connections between adjacent tissues during development. We have investigated here the role of Rb during development of the olfactory system (OS), which heavily relies on reciprocal interactions between the olfactory epithelium (OE) and the olfactory bulb (OB). We show that mice carrying a telencephalic-specific deletion of Rb display several neurogenic defects in the OS during late development. In the OE, loss of Rb leads to ectopic proliferation of late-born progenitors (Tuj-1+), abnormal radial migration and terminal maturation of olfactory sensory neurons (OSNs). In the OB, deletion of Rb causes severe lamination defects with loss of clear boundaries between distinct layers. Importantly, starting around E15.5 when OB glomerulogenesis is initiated, many OSNs axons that project along the olfactory nerve layer (ONL) fail to properly innervate the nascent bulb, thus resulting in partial loss of connectivity between OE-OB and gradual neuronal degeneration in both tissues peaking at birth. This deficiency correlates with deregulated expressions of two key chemo-repellant molecules, Robo2/Slit1 and Nrp2/Sema3F that control the formation of dorsal-ventral topographic map of OSNs connections with OB glomeruli. This study highlights a critical requirement for Rb during neurogenesis and the establishment of proper synaptic connections inside the OS during development. PMID:27667971

  9. Morphological study on the olfactory systems of the snapping turtle, Chelydra serpentina.

    PubMed

    Nakamuta, Nobuaki; Nakamuta, Shoko; Kato, Hideaki; Yamamoto, Yoshio

    2016-06-01

    In this study, the olfactory system of a semi-aquatic turtle, the snapping turtle, has been morphologically investigated by electron microscopy, immunohistochemistry, and lectin histochemistry. The nasal cavity of snapping turtle was divided into the upper and lower chambers, lined by the sensory epithelium containing ciliated and non-ciliated olfactory receptor neurons, respectively. Each neuron expressed both Gαolf, the α-subunit of G-proteins coupling to the odorant receptors, and Gαo, the α-subunit of G-proteins coupling to the type 2 vomeronasal receptors. The axons originating from the upper chamber epithelium projected to the ventral part of the olfactory bulb, while those from the lower chamber epithelium to the dorsal part of the olfactory bulb. Despite the identical expression of G-protein α-subunits in the olfactory receptor neurons, these two projections were clearly distinguished from each other by the differential expression of glycoconjugates. In conclusion, these data indicate the presence of two types of olfactory systems in the snapping turtle. Topographic arrangement of the upper and lower chambers and lack of the associated glands in the lower chamber epithelium suggest their possible involvement in the detection of odorants: upper chamber epithelium in the air and the lower chamber epithelium in the water.

  10. Remyelination of the nonhuman primate spinal cord by transplantation of H-transferase transgenic adult pig olfactory ensheathing cells

    PubMed Central

    Radtke, Christine; Akiyama, Yukinori; Brokaw, Jane; Lankford, Karen L.; Wewetzer, Konstantin; Fodor, William L.; Kocsis, Jeffery D.

    2008-01-01

    Olfactory ensheathing cells (OECs) have been shown to mediate remyelination and to stimulate axonal regeneration in a number of in vivo rodent spinal cord studies. However, whether OECs display similar properties in the primate model has not been tested so far. In the present study, we thus transplanted highly-purified OECs isolated from transgenic pigs expressing the α1,2 fucosyltransferase gene (H-transferase or HT) gene into a demyelinated lesion of the African green monkey spinal cord. Four weeks posttransplantation, robust remyelination was found in 62.5% of the lesion sites, whereas there was virtually no remyelination in the nontransplanted controls. This together with the immunohistochemical demonstration of the grafted cells within the lesioned area confirmed that remyelination was indeed achieved by OECs. Additional in vitro assays demonstrated 1) that the applied cell suspension consisted of >98% OECs, 2) that the majority of the cells expressed the transgene, and 3) that expression of the HT gene reduced complement activation more than twofold compared with the nontransgenic control. This is the first demonstration that xenotransplantation of characterized OECs into the primate spinal cord results in remyelination. PMID:14657003

  11. The lack of protective effects of tea supplementation on liver and jejunal epithelium in adult rats exposed to cadmium and lead.

    PubMed

    Tomaszewska, Ewa; Winiarska-Mieczan, Anna; Dobrowolski, Piotr

    2015-11-01

    Adult rats at the age of 12 weeks were divided into the control group and groups supplemented with green (GT), black (BT), red (RT), or white (WT) tea extracts. The diet (except that for the control) was mixed with 7 mg Cd/kg and 50 mg Pb/kg. The experiment lasted 12 weeks. Basal haematology and plasma biochemical parameters as well as the histomorphometrical parameters of jejunal epithelium and liver were determined. The lowest body mass was found in the RT and WT groups. Some functional (increased plasma ALT and AST, and the de Ritis coefficient) and structural changes in the liver (slight fatty degenerative changes, an increase in the intercellular space) were evident irrespective of the type of tea in the Cd and Pb poisoned rats. This toxic effect was visible especially in rats drinking black or red tea. However, the rats had no elevated LDH and ALT activities. The highest content of Cd and Pb in the liver and blood plasma was found in rats drinking red tea. Based on the results obtained, it is clear that long-term exposure of adult rats with a mature intestinal barrier to Cd and Pb contamination, under higher exposure conditions than the current estimates of weekly exposure of the general population to Cd and Pb through diet, causes a toxic effect, especially in the liver, and can change the structure of intestinal mucosa, irrespective of tea administration.

  12. Laminar disorganisation of mitral cells in the olfactory bulb does not affect topographic targeting of primary olfactory axons.

    PubMed

    Royal, S J; Gambello, M J; Wynshaw-Boris, A; Key, B; Clarris, H J

    2002-04-05

    Primary olfactory neurons expressing the same odorant receptor protein typically project to topographically fixed olfactory bulb sites. While cell adhesion molecules and odorant receptors have been implicated in guidance of primary olfactory axons, the postsynaptic mitral cells may also have a role in final target selection. We have examined the effect of disorganisation of the mitral cell soma layer in mutant mice heterozygous for the beta-subunit of platelet activating factor acetylhydrolase (Lis1(-/+)) on the targeting of primary olfactory axons. Lis1(-/+) mice display abnormal lamination of neurons in the olfactory bulb. Lis1(-/+) mice were crossed with the P2-IRES-tau:LacZ line of transgenic mice that selectively expresses beta-galactosidase in primary olfactory neurons expressing the P2 odorant receptor. LacZ histochemistry revealed blue-stained P2 axons that targeted topographically fixed glomeruli in these mice in a manner similar to that observed in the parent P2-IRES-tau:LacZ line. Thus, despite the aberrant organisation of postsynaptic mitral cells in Lis1(-/+) mice, primary olfactory axons continued to converge and form glomeruli at correct sites in the olfactory bulb. Next we examined whether challenging primary olfactory axons in adult Lis(-/+) mice with regeneration would affect their ability to converge and form glomeruli. Following partial chemical ablation of the olfactory neuroepithelium with dichlobenil, primary olfactory neurons die and are replaced by newly differentiating neurons that project axons to the olfactory bulb where they converge and form glomeruli. Despite the aberrant mitral cell layer in Lis(-/+) mice, primary olfactory axons continued to converge and form glomeruli during regeneration. Together these results demonstrate that the convergence of primary olfactory axons during development and regeneration is not affected by gross perturbations to the lamination of the mitral cell layer. Thus, these results support evidence from

  13. Magnetite-Based Magnetoreceptor Cells in the Olfactory Organ of Rainbow Trout and Zebrafish

    NASA Astrophysics Data System (ADS)

    Kirschvink, J. L.; Cadiou, H.; Dixson, A. D.; Eder, S.; Kobayashi, A.; McNaughton, P. A.; Muhamad, A. N.; Raub, T. D.; Walker, M. M.; Winklhofer, M.; Yuen, B. B.

    2011-12-01

    Many vertebrate and invertebrate animals have a geomagnetic sensory system, but the biophysics and anatomy of how magnetic stimuli are transduced to the nervous system is a challenging problem. Previous work in our laboratories identified single-domain magnetite chains in olfactory epithelium in cells proximal to the ros V nerve, which, in rainbow trout, responds to magnetic fields. Our objectives are to characterize these magnetite-containing cells and determine whether they form part of the mechanism of magnetic field transduction in teleost fishes, as a model for other Vertebrates. Using a combination of reflection mode confocal microscopy and a Prussian Blue technique modified to stain specifically for magnetite, our Auckland group estimated that both juvenile rainbow trout (ca. 7 cm total length) olfactory rosettes have ~200 magnetite-containing cells. The magnetite present in two types of cells within the olfactory epithelium appears to be arranged in intracellular chains. All of our groups (Munich, Auckland, Cambridge and Caltech) have obtained different types of structural evidence that magnetite chains closely associate with the plasma membrane in the cells, even in disaggregated tissues. In addition, our Cambridge group used Ca2+ imaging to demonstrate a clear response by individual magnetite-containing cells to a step change in the intensity of the external magnetic field and a slow change in Ca2+ activity when the external magnetic field was cancelled. In the teleost, zebrafish (Danio rerio), a small (~4 cm adult length in captivity) genetic and developmental biology model organism, our Caltech group detected ferromagnetic material throughout the body, but concentrated in the rostral trunk, using NRM and IRM scans of whole adults. Our analysis suggests greater than one million, 80-100 nm crystals, with Lowrie-Fuller curves strongly consistent with single-domain magnetite in 100-100,000 magnetocytes. Ferromagentic resonance (FMR) spectra show crystals

  14. Effects of Neural Stem Cell and Olfactory Ensheathing Cell Co-transplants on Tissue Remodelling After Transient Focal Cerebral Ischemia in the Adult Rat.

    PubMed

    Augestad, Ingrid Lovise; Nyman, Axel Karl Gottfrid; Costa, Alex Ignatius; Barnett, Susan Carol; Sandvig, Axel; Håberg, Asta Kristine; Sandvig, Ioanna

    2017-01-24

    Effective transplant-mediated repair of ischemic brain lesions entails extensive tissue remodeling, especially in the ischemic core. Neural stem cells (NSCs) are promising reparative candidates for stroke induced lesions, however, their survival and integration with the host-tissue post-transplantation is poor. In this study, we address this challenge by testing whether co-grafting of NSCs with olfactory ensheathing cells (OECs), a special type of glia with proven neuroprotective, immunomodulatory, and angiogenic effects, can promote graft survival and host tissue remodelling. Transient focal cerebral ischemia was induced in adult rats by a 60-min middle cerebral artery occlusion (MCAo) followed by reperfusion. Ischemic lesions were verified by neurological testing and magnetic resonance imaging. Transplantation into the globus pallidus of NSCs alone or in combination with OECs was performed at two weeks post-MCAo, followed by histological analyses at three weeks post-transplantation. We found evidence of extensive vascular remodelling in the ischemic core as well as evidence of NSC motility away from the graft and into the infarct border in severely lesioned animals co-grafted with OECs. These findings support a possible role of OECs as part of an in situ tissue engineering paradigm for transplant mediated repair of ischemic brain lesions.

  15. Histological and lectin histochemical studies on the olfactory mucosae of the Korean roe deer, Capreolus pygargus.

    PubMed

    Park, Changnam; Ahn, Meejung; Kim, Jeongtae; Kim, Seungjoon; Moon, Changjong; Shin, Taekyun

    2015-04-01

    The morphological features of the olfactory mucosae of Korean roe deer, Capreolus pygargus, were histologically studied using the ethmoid turbinates containing the olfactory mucosae from six roe deer (male, 2-3 years old). The ethmoid turbinates were embedded in paraffin, and histochemically evaluated in terms of the mucosal characteristics. Lectin histochemistry was performed to investigate the carbohydrate-binding specificity on the olfactory mucosa. Lectins, including Triticum vulgaris wheat germ agglutinin (WGA), Ulex europaeus agglutinin I (UEA-I), and soybean agglutinin (SBA) were used for the N-acetylglucosamine, fucose and N-acetylgalactosamine carbohydrate groups, respectively. Histologically, the olfactory mucosa, positioned mainly in the caudal roof of the nasal cavity, consisted of the olfactory epithelium and the lamina propria. The olfactory epithelium consisted of protein gene product (PGP) 9.5-positive olfactory receptor cells, galectin-3-positive supporting cells and basal cells. Bowman's glands in the lamina propria were stained by both the periodic acid Schiff reagent and alcian blue (pH 2.5). Two types of lectin, WGA and SBA, were labeled in free border, receptor cells, supporting cells and Bowman's glands, with the exception of basal cells, while UEA-I was labeled in free border, supporting cells and Bowman's glands, but not in receptor cells and basal cells, suggesting that carbohydrate terminals on the olfactory mucosae of roe deer vary depending on cell type. This is the first morphological study of the olfactory mucosa of the Korean roe deer to evaluate carbohydrate terminals in the olfactory mucosae.

  16. Information processing in the mammalian olfactory system.

    PubMed

    Lledo, Pierre-Marie; Gheusi, Gilles; Vincent, Jean-Didier

    2005-01-01

    Recently, modern neuroscience has made considerable progress in understanding how the brain perceives, discriminates, and recognizes odorant molecules. This growing knowledge took over when the sense of smell was no longer considered only as a matter for poetry or the perfume industry. Over the last decades, chemical senses captured the attention of scientists who started to investigate the different stages of olfactory pathways. Distinct fields such as genetic, biochemistry, cellular biology, neurophysiology, and behavior have contributed to provide a picture of how odor information is processed in the olfactory system as it moves from the periphery to higher areas of the brain. So far, the combination of these approaches has been most effective at the cellular level, but there are already signs, and even greater hope, that the same is gradually happening at the systems level. This review summarizes the current ideas concerning the cellular mechanisms and organizational strategies used by the olfactory system to process olfactory information. We present findings that exemplified the high degree of olfactory plasticity, with special emphasis on the first central relay of the olfactory system. Recent observations supporting the necessity of such plasticity for adult brain functions are also discussed. Due to space constraints, this review focuses mainly on the olfactory systems of vertebrates, and primarily those of mammals.

  17. The electrophysiology of the olfactory-hippocampal circuit in the isolated and perfused adult mammalian brain in vitro.

    PubMed

    de Curtis, M; Paré, D; Llinás, R R

    1991-10-01

    The viability and general electrophysiological properties of the limbic system in the adult mammalian brain isolated and maintained in vitro by arterial perfusion are described. The isolated brain preparation combines the advantages of intact synaptic connectivity and accessibility of different areas of the encephalic mass with those of the in vitro approach, i.e., stability and control of the ionic environment. Extracellular field potential as well as intracellular recordings were performed at different levels in the limbic system of isolated adult guinea pig brains. The results demonstrate that in the piriform, entorhinal, and hippocampal cortices, the intrinsic electrical properties of individual cells as well as the spontaneous and evoked electrical activity in the neuronal ensembles they comprise, were virtually identical to those observed in vivo. The properties of the limbic system loop were determined.

  18. The Dlx5 and Foxg1 transcription factors, linked via miRNA-9 and -200, are required for the development of the olfactory and GnRH system.

    PubMed

    Garaffo, Giulia; Conte, Daniele; Provero, Paolo; Tomaiuolo, Daniela; Luo, Zheng; Pinciroli, Patrizia; Peano, Clelia; D'Atri, Ilaria; Gitton, Yorick; Etzion, Talya; Gothilf, Yoav; Gays, Dafne; Santoro, Massimo M; Merlo, Giorgio R

    2015-09-01

    During neuronal development and maturation, microRNAs (miRs) play diverse functions ranging from early patterning, proliferation and commitment to differentiation, survival, homeostasis, activity and plasticity of more mature and adult neurons. The role of miRs in the differentiation of olfactory receptor neurons (ORNs) is emerging from the conditional inactivation of Dicer in immature ORN, and the depletion of all mature miRs in this system. Here, we identify specific miRs involved in olfactory development, by focusing on mice null for Dlx5, a homeogene essential for both ORN differentiation and axon guidance and connectivity. Analysis of miR expression in Dlx5(-/-) olfactory epithelium pointed to reduced levels of miR-9, miR-376a and four miRs of the -200 class in the absence of Dlx5. To functionally examine the role of these miRs, we depleted miR-9 and miR-200 class in reporter zebrafish embryos and observed delayed ORN differentiation, altered axonal trajectory/targeting, and altered genesis and position of olfactory-associated GnRH neurons, i.e. a phenotype known as Kallmann syndrome in humans. miR-9 and miR-200-class negatively control Foxg1 mRNA, a fork-head transcription factor essential for development of the olfactory epithelium and of the forebrain, known to maintain progenitors in a stem state. Increased levels of z-foxg1 mRNA resulted in delayed ORN differentiation and altered axon trajectory, in zebrafish embryos. This work describes for the first time the role of specific miR (-9 and -200) in olfactory/GnRH development, and uncovers a Dlx5-Foxg1 regulation whose alteration affects receptor neuron differentiation, axonal targeting, GnRH neuron development, the hallmarks of the Kallmann syndrome.

  19. The Pig Olfactory Brain: A Primer

    PubMed Central

    Feldman, Sanford; Osterberg, Stephen K.

    2016-01-01

    Despite the fact that pigs are reputed to have excellent olfactory abilities, few studies have examined regions of the pig brain involved in the sense of smell. The present study provides an overview of the olfactory bulb, anterior olfactory nucleus, and piriform cortex of adult pigs using several approaches. Nissl, myelin, and Golgi stains were used to produce a general overview of the organization of the regions and confocal microscopy was employed to examine 1) projection neurons, 2) GABAergic local circuit neurons that express somatostatin, parvalbumin, vasoactive intestinal polypeptide, or calretinin, 3) neuromodulatory fibers (cholinergic and serotonergic), and 4) glia (astrocytes and microglia). The findings revealed that pig olfactory structures are quite large, highly organized and follow the general patterns observed in mammals. PMID:26936231

  20. The development of the olfactory organs in newly hatched monotremes and neonate marsupials.

    PubMed

    Schneider, Nanette Yvette

    2011-08-01

    Olfactory cues are thought to play a crucial role in the detection of the milk source at birth in mammals. It has been shown that a marsupial, the tammar wallaby, can detect olfactory cues from its mother's pouch at birth. This study investigates whether the main olfactory and accessory olfactory system are similarly well developed in other marsupials and monotremes at birth/hatching as in the tammar. Sections of the head of various marsupial and two monotreme species were investigated by light microscopy. Both olfactory systems were less well developed in the kowari and Eastern quoll. No olfactory or vomeronasal or terminal nerves could be observed; the main olfactory bulb (MOB) had only two layers while no accessory olfactory bulb or ganglion terminale were visible. All other investigated marsupials and monotremes showed further developed olfactory systems with olfactory, vomeronasal and terminal nerves, a three-layered MOB, and in the marsupials a prominent ganglion terminale. The main olfactory system was further developed than the accessory olfactory system in all species investigated. The olfactory systems were the least developed in species in which the mother's birth position removed most of the difficulty in reaching the teat, placing the neonate directly in the pouch. In monotremes they were the furthest developed as Bowman glands were found underlying the main olfactory epithelium. This may reflect the need to locate the milk field each time they drink as they cannot permanently attach to it, unlike therian mammals. While it still needs to be determined how an odour signal could be further processed in the brain, this study suggests that marsupials and monotremes possess well enough developed olfactory systems to be able to detect an odour cue from the mammary area at birth/hatching. It is therefore likely that neonate marsupials and newly hatched monotremes find their way to the milk source using olfactory cues, as has been previously suggested for the

  1. The development of the olfactory organs in newly hatched monotremes and neonate marsupials

    PubMed Central

    Schneider, Nanette Yvette

    2011-01-01

    Olfactory cues are thought to play a crucial role in the detection of the milk source at birth in mammals. It has been shown that a marsupial, the tammar wallaby, can detect olfactory cues from its mother's pouch at birth. This study investigates whether the main olfactory and accessory olfactory system are similarly well developed in other marsupials and monotremes at birth/hatching as in the tammar. Sections of the head of various marsupial and two monotreme species were investigated by light microscopy. Both olfactory systems were less well developed in the kowari and Eastern quoll. No olfactory or vomeronasal or terminal nerves could be observed; the main olfactory bulb (MOB) had only two layers while no accessory olfactory bulb or ganglion terminale were visible. All other investigated marsupials and monotremes showed further developed olfactory systems with olfactory, vomeronasal and terminal nerves, a three-layered MOB, and in the marsupials a prominent ganglion terminale. The main olfactory system was further developed than the accessory olfactory system in all species investigated. The olfactory systems were the least developed in species in which the mother's birth position removed most of the difficulty in reaching the teat, placing the neonate directly in the pouch. In monotremes they were the furthest developed as Bowman glands were found underlying the main olfactory epithelium. This may reflect the need to locate the milk field each time they drink as they cannot permanently attach to it, unlike therian mammals. While it still needs to be determined how an odour signal could be further processed in the brain, this study suggests that marsupials and monotremes possess well enough developed olfactory systems to be able to detect an odour cue from the mammary area at birth/hatching. It is therefore likely that neonate marsupials and newly hatched monotremes find their way to the milk source using olfactory cues, as has been previously suggested for the

  2. Innate olfactory preferences in dung beetles.

    PubMed

    Dormont, Laurent; Jay-Robert, Pierre; Bessière, Jean-Marie; Rapior, Sylvie; Lumaret, Jean-Pierre

    2010-09-15

    The effects of insect larval diet on adult olfactory responses to host-plant or food volatiles are still debated. The induction of adult host preferences has been studied in insects with diverse ecologies, including parasitoids, flower-visitors and phytophagous species. We investigated this question for the first time in a coprophagous insect species. Larvae of the French scarab dung beetle Agrilinus constans were reared on four different artificial substrates containing dung from cattle, horse, sheep or wild boar, and responses of imagos to dung volatiles were then behaviourally tested in an olfactometer. We also reported the first analysis of the composition of different mammal dung volatiles. We showed that adult beetles were more attracted to cattle and sheep dung odours, and that larval feeding experience had no effect on the adult olfactory responses to dung volatiles. A second experiment showed that the presence of other insects inside the dung resource affects the process of dung selection by adults. We identified 64 chemical compounds from dung emissions, and showed that dung volatiles clearly differed among different mammal species, allowing olfactory discrimination by dung beetles. Our results suggest that resource selection in coprophagous insects may be based on innate olfactory preferences. Further experiments should examine whether Agrilinus adults can learn new dung odours, and whether larval diet may influence the behaviour of adults in other coprophagous species.

  3. Localization of α1-2 Fucose Glycan in the Mouse Olfactory Pathway.

    PubMed

    Kondoh, Daisuke; Kamikawa, Akihiro; Sasaki, Motoki; Kitamura, Nobuo

    2017-01-01

    Glycoconjugates in the olfactory system play critical roles in neuronal formation, and α1-2 fucose (α1-2Fuc) glycan mediates neurite outgrowth and synaptic plasticity. Histochemical findings of α1-2Fuc glycan in the mouse olfactory system detected using Ulex europaeus agglutinin-I (UEA-I) vary. This study histochemically assessed the main olfactory and vomeronasal pathways in male and female ICR and C57BL/6J mice aged 3-4 months using UEA-I. Ulex europaeus agglutinin-I reacted with most receptor cells arranged mainly at the basal region of the olfactory epithelium. The olfactory nerve layer and glomerular layer of the main olfactory bulb were speckled with positive UEA-I staining, and positive fibers were scattered from the glomerular to the internal plexiform layer. The lateral olfactory tract and rostral migratory stream were also positive for UEA-I. We identified superficial short-axon cells, interneurons of the external plexiform layer, external, middle and internal tufted cells, mitral cells and granule cells as the origins of the UEA-I-positive fibers in the main olfactory bulb. The anterior olfactory nucleus, anterior piriform cortex and olfactory tubercle were negative for UEA-I. Most receptor cells in the vomeronasal epithelium and most glomeruli of the accessory olfactory bulb were positive for UEA-I. Our findings indicated that α1-2Fuc glycan is located within the primary and secondary, but not the ternary, pathways of the main olfactory system, in local circuits of the main olfactory bulb and within the primary, but not secondary, pathway of the vomeronasal system.

  4. The morphology and kinetics of spermatogonial degeneration in normal adult rats: an analysis using a simplified classification of the germinal epithelium.

    PubMed

    Huckins, C

    1978-04-01

    The phenomena of spermatogonial degeneration have been studied in normal adult rat testes using a simplified classification of the germinal epthelium based upon the six types of differentiating spermatogonia. The following features distinguished this from schemes based on acrosome development. Rather than 14 states of unequal duration, there are only six stages, five of which are the same length. The classification starts at the beginning of spermatogenesis with A1 spermatogonia rather than at the onset of spermiogenesis. The classification is derived from acutal biological events in spermatogenesis, namely generation times of spermatogonia, rather than upon arbitrary events in acrosome development. Most importantly, this new classification can be used with most types of preparations and in most experimental conditions. Examination of tubular whole mounts reveals that degeneration preferentially occurs in types A2 and A3 and to a lesser extent A4 spermatogonia, and is rarely seen in generations of A1, In or B cells. Deterioration is first manifested in clusters of cells joined by the intercellular bridges as they complete DNA synthesis and enter the 2 phase of cell cycle. It is characterized by a denser staining of the nuclear membrane, coalescence of chromatin into several pyknotic bodies, and eventual extrusion of the nuclear mass, leaving a cytoplasmic ghost. The sequential steps in degeneration may often be traced from one end of a synctial chain to the other, suggesting that the process may start with just one cell and then spread via intercellular bridges to involve all spermatogonia within the clone. Quanitatively, degeneration is a relatively constant feature of spermatogonial development. Only 25% of the theoretically possible number of pre-leptotene spermatocytes are produced from th original population of A1 spermatogonia; most of this loss is incurred during the maturation of A2 and A3 generations. While the reason for spermatogonial degeneration in the

  5. The immunolocalization of small nuclear ribonucleoprotein particles in testicular cells during the cycle of the seminiferous epithelium of the adult rat.

    PubMed

    Moussa, F; Oko, R; Hermo, L

    1994-11-01

    The objective of this study was to determine the cellular and subcellular distribution of small nuclear ribonucleoprotein particles (snRNPs) in the adult rat testis in relation to the different cell types at the various stages of the cycle of the seminiferous epithelium. The distribution of snRNPs in the nucleus and cytoplasm of germ cells was quantitated in an attempt to correlate RNA processing with morphological and functional changes occurring during the development of these cells. Light-microscopic immunoperoxidase staining of rat testes with polyclonal anti-Sm and monoclonal anti-Y12 antibodies localized spliceosome snRNPs in the nuclei and cytoplasm of germ cells up to step 10 spermatids. Nuclear staining was intense in Sertoli cells, spermatogonia, spermatocytes, and in the early steps of round spermatid development. Although comparatively weaker, cytoplasmic staining for snRNPs was strongest in mid and late pachytene spermatocytes and early round spermatids. Quantitative electron-microscopic immunogold labeling of Lowicryl embedded testicular sections confirmed the light-microscopic observations but additionally showed that the snRNP content peaked in the cytoplasm of midpachytene spermatocytes and in the nuclei of late pachytene spermatocytes. The immunogold label tended to aggregate into distinct loci over the nuclear chromatin. The chromatoid body of spermatids and spermatocytes and the finely granular material in the interstices of mitochondrial aggregates of spermatocytes were found to be additional sites of snRNP localization and were intensely labeled. This colocalization suggests that these dense cytoplasmic structures may be functionally related. Anti-U1 snRNP antibodies applied to frozen sections showed the same LM localization pattern as spliceosome snRNPs. Anti-U3 snRNP antibodies applied to frozen sections stained nucleoli of germ cells where pre-rRNA is spliced.

  6. Delayed olfactory nerve regeneration in ApoE-deficient mice.

    PubMed

    Nathan, Britto P; Nisar, Rafia; Short, Jody; Randall, Shari; Grissom, Elin; Griffin, Gwen; Switzer, Paul V; Struble, Robert G

    2005-04-11

    Apolipoprotein E (apoE), a lipid transporting protein, is extensively expressed in the primary olfactory pathway, but its function is unknown. We previously reported increased apoE levels in the olfactory bulb (OB) following olfactory epithelium (OE) lesion in mice, and hypothesized that apoE may play a vital role in olfactory nerve (ON) regeneration. To directly test this hypothesis, we examined the rate of ON regeneration following OE lesion in apoE deficient/knockout (KO) and wild-type (WT) mice. OE was lesioned in 2- to 3-month-old mice by intranasal irrigation with Triton X-100 (TX). OB were collected at 0, 3, 7, 21, 42, and 56 days post-lesion. OB recovery was measured by both immunoblotting and immunohistochemical analysis of growth cone associated protein (GAP) 43 and olfactory marker protein (OMP). The results revealed that (1) OMP recovery in the OB was significantly slower in apoE KO compared to WT mice; (2) recovery of glomerular area was similarly slower; and (3) GAP43 increases and return to prelesion levels in the OB were slower in KO mice. Together, these results show that olfactory nerve regeneration is significantly slower in KO mice as compared to WT mice, suggesting apoE facilitates olfactory nerve regeneration.

  7. Encoding olfactory signals via multiple chemosensory systems.

    PubMed

    Ma, Minghong

    2007-01-01

    Most animals have evolved multiple olfactory systems to detect general odors as well as social cues. The sophistication and interaction of these systems permit precise detection of food, danger, and mates, all crucial elements for survival. In most mammals, the nose contains two well described chemosensory apparatuses (the main olfactory epithelium and the vomeronasal organ), each of which comprises several subtypes of sensory neurons expressing distinct receptors and signal transduction machineries. In many species (e.g., rodents), the nasal cavity also includes two spatially segregated clusters of neurons forming the septal organ of Masera and the Grueneberg ganglion. Results of recent studies suggest that these chemosensory systems perceive diverse but overlapping olfactory cues and that some neurons may even detect the pressure changes carried by the airflow. This review provides an update on how chemosensory neurons transduce chemical (and possibly mechanical) stimuli into electrical signals, and what information each system brings into the brain. Future investigation will focus on the specific ligands that each system detects with a behavioral context and the processing networks that each system involves in the brain. Such studies will lead to a better understanding of how the multiple olfactory systems, acting in concert, offer a complete representation of the chemical world.

  8. Histochemical and ultrastructural analyses of the lubrication systems in the olfactory organs of soft-shelled turtle

    PubMed Central

    NAKAMUTA, Shoko; YOKOSUKA, Makoto; TANIGUCHI, Kazumi; YAMAMOTO, Yoshio; NAKAMUTA, Nobuaki

    2016-01-01

    In general, the nasal cavity of turtles is divided into two chambers: the upper chamber, lined with the olfactory epithelium containing ciliated olfactory receptor cells, and the lower chamber, lined with the vomeronasal epithelium containing microvillous receptor cells. In the nasal cavity of soft-shelled turtles, however, differences between the upper and lower chamber epithelia are unclear due to the presence of ciliated receptor cells in both epithelia. In the olfactory organ of vertebrates, the surface of sensory epithelium is covered with secretory products of associated glands and supporting cells, playing important roles in the olfaction by dissolving odorants and transporting them to the olfactory receptors. Here, the associated glands and supporting cells in the olfactory organ of soft-shelled turtles were analyzed histochemically and ultrastructurally. The upper chamber epithelium possessed associated glands, constituted by cells containing serous secretory granules; whereas, the lower chamber epithelium did not. In the upper chamber epithelium, secretory granules filled the supranuclear region of supporting cells, while most of the granules were distributed near the free border of supporting cells in the lower chamber epithelium. The secretory granules in the supporting cells of both epithelia were seromucous, but alcian blue stained them differently from each other. In addition, distinct expression of carbohydrates was suggested by the differences in lectin binding. These data indicate the quantitative and qualitative differences in the secretory properties between the upper and lower chamber epithelia, suggesting their distinct roles in the olfaction. PMID:26782135

  9. Gross anatomy and histology of the olfactory rosette of the shark Heptranchias perlo.

    PubMed

    Ferrando, Sara; Gallus, Lorenzo; Amaroli, Andrea; Gambardella, Chiara; Waryani, Baradi; Di Blasi, Davide; Vacchi, Marino

    2017-02-17

    Sharks belonging to the family Hexanchidae have six or seven gill slits, unlike all other elasmobranchs, which have five gill slits. Their olfactory organs have a round shape, which is common for holocephalans, but not for elasmobranchs. Thus, the shape of the olfactory organ represents a further, less striking, peculiarity of this family among elasmobranchs. Despite that, the microscopic anatomy and histology of the olfactory organ have not yet been studied in any species of this family. Here, an anatomical and histological description of the olfactory organ of the sharpnose sevengill shark Heptranchias perlo is given. The organ is a rosette, with a central raphe and 31-34 primary lamellae, which bear secondary lamellae with a more or less branched shape. The elastic connective capsule which envelops the olfactory rosette possibly changes its shape along with water influx. In the olfactory epithelium, the supporting cells also have a secretory function, while no specialized mucous cells are visible; regarding this feature the olfactory epithelium of H. perlo differs from that of other chondrichthyan species. The immunohistochemical investigation of the sensory epithelium shows the absence of immunoreactivity for Gαolf in receptor neurons, which confirms previous observations in Chondrichthyes.

  10. Ability of transplanted cultured epithelium to respond to dermal papillae.

    PubMed

    Xing, L; Kobayashi, K

    2001-10-01

    Cultured epithelium has been used successfully in the treatment of extensive burns. Regenerated epidermis, however, lacks such as hair follicles and sweat glands that are common in mammalian skin. We attempted to determine whether cultured epithelium could be induced to form hair follicles by dermal papillae, which are most important for the morphogenesis and growth of hair follicles. We cultivated adult rat sole keratinocytes, obtained the cultured epithelium, and prepared recombinants consisting of cultured epithelium and fresh dermal papillae with or without the sole dermis. These recombinants were then transplanted underneath the dermis of the dorsal skin of syngeneic rats or athymic mice. Histologic examination revealed that the transplanted cultured epithelium formed the follicular structures with sebaceous gland-like structure following induction of the dermal papillae, especially when supported by the dermis. We concluded that transplanted cultured epithelium of adult rat sole keratinocytes can respond to growth signals from adult dermal papillae.

  11. Nasal Administration of Cholera Toxin as a Mucosal Adjuvant Damages the Olfactory System in Mice

    PubMed Central

    Fukuyama, Yoshiko; Okada, Kazunari; Yamaguchi, Masahiro; Kiyono, Hiroshi; Mori, Kensaku; Yuki, Yoshikazu

    2015-01-01

    Cholera toxin (CT) induces severe diarrhea in humans but acts as an adjuvant to enhance immune responses to vaccines when administered orally. Nasally administered CT also acts as an adjuvant, but CT and CT derivatives, including the B subunit of CT (CTB), are taken up from the olfactory epithelium and transported to the olfactory bulbs and therefore may be toxic to the central nervous system. To assess the toxicity, we investigated whether nasally administered CT or CT derivatives impair the olfactory system. In mice, nasal administration of CT, but not CTB or a non-toxic CT derivative, reduced the expression of olfactory marker protein (OMP) in the olfactory epithelium and olfactory bulbs and impaired odor responses, as determined with behavioral tests and optical imaging. Thus, nasally administered CT, like orally administered CT, is toxic and damages the olfactory system in mice. However, CTB and a non-toxic CT derivative, do not damage the olfactory system. The optical imaging we used here will be useful for assessing the safety of nasal vaccines and adjuvants during their development for human use and CT can be used as a positive control in this test. PMID:26422280

  12. Calcium-activated chloride currents in olfactory sensory neurons from mice lacking bestrophin-2.

    PubMed

    Pifferi, Simone; Dibattista, Michele; Sagheddu, Claudia; Boccaccio, Anna; Al Qteishat, Ahmed; Ghirardi, Filippo; Tirindelli, Roberto; Menini, Anna

    2009-09-01

    Olfactory sensory neurons use a chloride-based signal amplification mechanism to detect odorants. The binding of odorants to receptors in the cilia of olfactory sensory neurons activates a transduction cascade that involves the opening of cyclic nucleotide-gated channels and the entry of Ca(2+) into the cilia. Ca(2+) activates a Cl(-) current that produces an efflux of Cl(-) ions and amplifies the depolarization. The molecular identity of Ca(2+)-activated Cl(-) channels is still elusive, although some bestrophins have been shown to function as Ca(2+)-activated Cl(-) channels when expressed in heterologous systems. In the olfactory epithelium, bestrophin-2 (Best2) has been indicated as a candidate for being a molecular component of the olfactory Ca(2+)-activated Cl(-) channel. In this study, we have analysed mice lacking Best2. We compared the electrophysiological responses of the olfactory epithelium to odorant stimulation, as well as the properties of Ca(2+)-activated Cl(-) currents in wild-type (WT) and knockout (KO) mice for Best2. Our results confirm that Best2 is expressed in the cilia of olfactory sensory neurons, while odorant responses and Ca(2+)-activated Cl(-) currents were not significantly different between WT and KO mice. Thus, Best2 does not appear to be the main molecular component of the olfactory channel. Further studies are required to determine the function of Best2 in the cilia of olfactory sensory neurons.

  13. Calcium-activated chloride currents in olfactory sensory neurons from mice lacking bestrophin-2

    PubMed Central

    Pifferi, Simone; Dibattista, Michele; Sagheddu, Claudia; Boccaccio, Anna; Al Qteishat, Ahmed; Ghirardi, Filippo; Tirindelli, Roberto; Menini, Anna

    2009-01-01

    Olfactory sensory neurons use a chloride-based signal amplification mechanism to detect odorants. The binding of odorants to receptors in the cilia of olfactory sensory neurons activates a transduction cascade that involves the opening of cyclic nucleotide-gated channels and the entry of Ca2+ into the cilia. Ca2+ activates a Cl− current that produces an efflux of Cl− ions and amplifies the depolarization. The molecular identity of Ca2+-activated Cl− channels is still elusive, although some bestrophins have been shown to function as Ca2+-activated Cl− channels when expressed in heterologous systems. In the olfactory epithelium, bestrophin-2 (Best2) has been indicated as a candidate for being a molecular component of the olfactory Ca2+-activated Cl− channel. In this study, we have analysed mice lacking Best2. We compared the electrophysiological responses of the olfactory epithelium to odorant stimulation, as well as the properties of Ca2+-activated Cl− currents in wild-type (WT) and knockout (KO) mice for Best2. Our results confirm that Best2 is expressed in the cilia of olfactory sensory neurons, while odorant responses and Ca2+-activated Cl− currents were not significantly different between WT and KO mice. Thus, Best2 does not appear to be the main molecular component of the olfactory channel. Further studies are required to determine the function of Best2 in the cilia of olfactory sensory neurons. PMID:19622610

  14. Cellular basis for the olfactory response to nicotine.

    PubMed

    Bryant, Bruce; Xu, Jiang; Audige, Valery; Lischka, Fritz W; Rawson, Nancy E

    2010-03-17

    Smokers regulate their smoking behavior on the basis of sensory stimuli independently of the pharmacological effects of nicotine (Rose J. E., et al. (1993) Pharmacol., Biochem. Behav.44 (4), 891-900). A better understanding of sensory mechanisms underlying smoking behavior may help to develop more effective smoking alternatives. Olfactory stimulation by nicotine makes up a considerable part of the flavor of tobacco smoke, yet our understanding of the cellular mechanisms responsible for olfactory detection of nicotine remains incomplete. We used biophysical methods to characterize the nicotine sensitivity and response mechanisms of neurons from olfactory epithelium. In view of substantial differences in the olfactory receptor repertoire between rodent and human (Mombaerts P. (1999) Annu. Rev. Neurosci.22, 487-509), we studied biopsied human olfactory sensory neurons (OSNs), cultured human olfactory cells (Gomez G., et al. (2000) J. Neurosci. Res.62 (5), 737-749), and rat olfactory neurons. Rat and human OSNs responded to S(-)-nicotine with a concentration dependent influx of calcium and activation of adenylate cyclase. Some rat OSNs displayed some stereoselectivity, with neurons responding to either enantiomer alone or to both. Freshly biopsied and primary cultured human olfactory neurons were less stereoselective. Nicotinic cholinergic antagonists had no effect on the responses of rat or human OSNs to nicotine. Patch clamp recording of rat OSNs revealed a nicotine-activated, calcium-sensitive nonspecific cation channel. These results indicate that nicotine activates a canonical olfactory receptor pathway rather than nicotinic cholinergic receptors on OSNs. Further, because the nicotine-sensitive mechanisms of rodents appear generally similar to those of humans, this animal model is an appropriate one for studies of nicotine sensation.

  15. The sea lamprey has a primordial accessory olfactory system

    PubMed Central

    2013-01-01

    Background A dual olfactory system, represented by two anatomically distinct but spatially proximate chemosensory epithelia that project to separate areas of the forebrain, is known in several classes of tetrapods. Lungfish are the earliest evolving vertebrates known to have this dual system, comprising a main olfactory and a vomeronasal system (VNO). Lampreys, a group of jawless vertebrates, have a single nasal capsule containing two anatomically distinct epithelia, the main (MOE) and the accessory olfactory epithelia (AOE). We speculated that lamprey AOE projects to specific telencephalic regions as a precursor to the tetrapod vomeronasal system. Results To test this hypothesis, we characterized the neural circuits and molecular profiles of the accessory olfactory epithelium in the sea lamprey (Petromyzon marinus). Neural tract-tracing revealed direct and reciprocal connections with the dorsomedial telencephalic neuropil (DTN) which in turn projects directly to the dorsal pallium and the rostral hypothalamus. High-throughput sequencing demonstrated that the main and the accessory olfactory epithelia have virtually identical profiles of expressed genes. Real time quantitative PCR confirmed expression of representatives of all 3 chemoreceptor gene families identified in the sea lamprey genome. Conclusion Anatomical and molecular evidence shows that the sea lamprey has a primordial accessory olfactory system that may serve a chemosensory function. PMID:23957559

  16. Trpc2 is expressed in two olfactory subsystems, the main and the vomeronasal system of larval Xenopus laevis.

    PubMed

    Sansone, Alfredo; Syed, Adnan S; Tantalaki, Evangelia; Korsching, Sigrun I; Manzini, Ivan

    2014-07-01

    Complete segregation of the main olfactory epithelium (MOE) and the vomeronasal epithelium is first observed in amphibians. In contrast, teleost fishes possess a single olfactory surface, in which genetic components of the main and vomeronasal olfactory systems are intermingled. The transient receptor potential channel TRPC2, a marker of vomeronasal neurons, is present in the single fish sensory surface, but is already restricted to the vomeronasal epithelium in a terrestrial amphibian, the red-legged salamander (Plethodon shermani). Here we examined the localization of TRPC2 in an aquatic amphibian and cloned the Xenopus laevis trpc2 gene. We show that it is expressed in both the MOE and the vomeronasal epithelium. This is the first description of a broad trpc2 expression in the MOE of a tetrapod. The expression pattern of trpc2 in the MOE is virtually undistinguishable from that of MOE-specific v2rs, indicating that they are co-expressed in the same neuronal subpopulation.

  17. Olfactory Learning in Individually Assayed Drosophila Larvae

    PubMed Central

    Scherer, Sabine; Stocker, Reinhard F.; Gerber, Bertram

    2003-01-01

    Insect and mammalian olfactory systems are strikingly similar. Therefore, Drosophila can be used as a simple model for olfaction and olfactory learning. The brain of adult Drosophila, however, is still complex. We therefore chose to work on the larva with its yet simpler but adult-like olfactory system and provide evidence for olfactory learning in individually assayed Drosophila larvae. We developed a differential conditioning paradigm in which odorants are paired with positive (“+” fructose) or negative (“-” quinine or sodium chloride) gustatory reinforcers. Test performance of individuals from two treatment conditions is compared—one received odorant A with the positive reinforcer and odorant B with a negative reinforcer (A+/B-); animals from the other treatment condition were trained reciprocally (A-/B+). During test, differences in choice between A and B of individuals having undergone either A+/B- or A-/B+ training therefore indicate associative learning. We provide such evidence for both combinations of reinforcers; this was replicable across repetitions, laboratories, and experimenters. We further show that breaks improve performance, in accord with basic principles of associative learning. The present individual assay will facilitate electrophysiological studies, which necessarily use individuals. As such approaches are established for the larval neuromuscular synapse, but not in adults, an individual larval learning paradigm will serve to link behavioral levels of analysis to synaptic physiology. PMID:12773586

  18. Histological and lectin histochemical studies on the olfactory and respiratory mucosae of the sheep.

    PubMed

    Ibrahim, Dalia; Nakamuta, Nobuaki; Taniguchi, Kazumi; Yamamoto, Yoshio; Taniguchi, Kazuyuki

    2014-03-01

    The olfactory and respiratory mucosae of the Corriedale sheep were examined using lectin histochemistry in order to clarify the histochemical and glycohistochemical differences between these two tissues. The olfactory epithelium was stained with 13 lectins out of 21 lectins examined, while the respiratory epithelium was positive to 16 lectins. The free border of both of the olfactory and respiratory epithelia was stained with 12 lectins: Wheat germ agglutinin (WGA), succinylated-wheat germ agglutinin (s-WGA), Lycopersicon esculentum lectin (LEL), Solanum tuberosum lectin (STL), Datura stramonium lectin (DSL), Soybean agglutinin (SBA), Bandeiraea simplicifolia lectin-I (BSL-I), Ricinus communis agglutinin-I (RCA-120), Erythrina cristagalli lectin (ECL), Concanavalin A (Con A), Phaseolus vulgaris agglutinin-E (PHA-E) and Phaseolus vulgaris agglutinin-L (PHA-L). The associated glands of the olfactory mucosa, Bowman's glands, were stained with 13 lectins. While both the goblet cells and mucous nasal glands were stained with 8 lectins; five of them (WGA, s-WGA, STL, Vicia villosa agglutinin (VVA) and ECL) were mutually positive among the Bowman's glands, mucous nasal glands and the goblet cells. These findings indicate that the glycohistochemical characteristics of the free borders of both olfactory and respiratory epithelia are similar to each other, suggesting that secretions from the Bowman's glands and those of the goblet cells and mucous nasal glands are partially exchanged between the surface of two epithelia to contribute the functions of the respiratory epithelium and the olfactory receptor cells, respectively.

  19. Posttraumatic olfactory dysfunction.

    PubMed

    Coelho, Daniel H; Costanzo, Richard M

    2016-04-01

    Impairment of smell may occur following injury to any portion of the olfactory tract, from nasal cavity to brain. A thorough understanding of the anatomy and pathophysiology combined with comprehensively obtained history, physical exam, olfactory testing, and neuroimaging may help to identify the mechanism of dysfunction and suggest possible treatments. Although most olfactory deficits are neuronal mediated and therefore currently unable to be corrected, promising technology may provide novel treatment options for those most affected. Until that day, patient counseling with compensatory strategies and reassurance is essential for the maintenance of safety and QoL in this unique and challenging patient population.

  20. Hypothalamus-olfactory system crosstalk: orexin a immunostaining in mice.

    PubMed

    Gascuel, Jean; Lemoine, Aleth; Rigault, Caroline; Datiche, Frédérique; Benani, Alexandre; Penicaud, Luc; Lopez-Mascaraque, Laura

    2012-01-01

    It is well known that olfaction influences food intake, and conversely, that an individual's nutritional status modulates olfactory sensitivity. However, what is still poorly understood is the neuronal correlate of this relationship, as well as the connections between the olfactory bulb and the hypothalamus. The goal of this report is to analyze the relationship between the olfactory bulb and hypothalamus, focusing on orexin A immunostaining, a hypothalamic neuropeptide that is thought to play a role in states of sleep/wakefulness. Interestingly, orexin A has also been described as a food intake stimulator. Such an effect may be due in part to the stimulation of the olfactory bulbar pathway. In rats, orexin positive cells are concentrated strictly in the lateral hypothalamus, while their projections invade nearly the entire brain including the olfactory system. Therefore, orexin appears to be a good candidate to play a pivotal role in connecting olfactory and hypothalamic pathways. So far, orexin has been described in rats, however, there is still a lack of information concerning its expression in the brains of adult and developing mice. In this context, we revisited the orexin A pattern in adult and developing mice using immunohistological methods and confocal microscopy. Besides minor differences, orexin A immunostaining in mice shares many features with those observed in rats. In the olfactory bulb, even though there are few orexin projections, they reach all the different layers of the olfactory bulb. In contrast to the presence of orexin projections in the main olfactory bulb, almost none have been found in the accessory olfactory bulb. The developmental expression of orexin A supports the hypothesis that orexin expression only appears post-natally.

  1. Optical recordings from the human nasal mucosa in response to olfactory stimulation.

    PubMed

    Ishimaru, Tadashi; Reden, Jens; Krone, Franziska; Scheibe, Mandy

    2007-08-23

    Using the intrinsic optical signal the present study aimed to investigate changes in blood flow at the nasal epithelium in response to specific olfactory stimulation. Recording equipment included an endoscope, a CCD camera, and a light source of 617 nm. Two concentrations of the specific olfactory stimulant H(2)S (2.8 and 5.6 ppm), generated by a computer-controlled olfactometer, were used for olfactory stimulation. Eight healthy normosmic volunteers participated. Using 5.6 ppm H(2)S stimuli, responses were typically recorded from the olfactory cleft, middle turbinate, and middle meatus while responses were less pronounced for 2.8 ppm H(2)S stimuli. Response areas were significantly larger for the 5.6 ppm H(2)S stimuli. While further experiments are needed, recordings of the intrinsic optical signal may be used to obtain responses from the nasal cavity to specific olfactory stimuli.

  2. A Screen for Genes Expressed in the Olfactory Organs of Drosophila melanogaster Identifies Genes Involved in Olfactory Behaviour

    PubMed Central

    Tunstall, Narelle E.; Herr, Anabel; de Bruyne, Marien; Warr, Coral G.

    2012-01-01

    Background For insects the sense of smell and associated olfactory-driven behaviours are essential for survival. Insects detect odorants with families of olfactory receptor proteins that are very different to those of mammals, and there are likely to be other unique genes and genetic pathways involved in the function and development of the insect olfactory system. Methodology/Principal Findings We have performed a genetic screen of a set of 505 Drosophila melanogaster gene trap insertion lines to identify novel genes expressed in the adult olfactory organs. We identified 16 lines with expression in the olfactory organs, many of which exhibited expression of the trapped genes in olfactory receptor neurons. Phenotypic analysis showed that six of the lines have decreased olfactory responses in a behavioural assay, and for one of these we showed that precise excision of the P element reverts the phenotype to wild type, confirming a role for the trapped gene in olfaction. To confirm the identity of the genes trapped in the lines we performed molecular analysis of some of the insertion sites. While for many lines the reported insertion sites were correct, we also demonstrated that for a number of lines the reported location of the element was incorrect, and in three lines there were in fact two pGT element insertions. Conclusions/Significance We identified 16 new genes expressed in the Drosophila olfactory organs, the majority in neurons, and for several of the gene trap lines demonstrated a defect in olfactory-driven behaviour. Further characterisation of these genes and their roles in olfactory system function and development will increase our understanding of how the insect olfactory system has evolved to perform the same essential function to that of mammals, but using very different molecular genetic mechanisms. PMID:22530061

  3. Trace amine-associated receptors are olfactory receptors in vertebrates.

    PubMed

    Liberles, Stephen D

    2009-07-01

    The mammalian nose is a powerful chemosensor, capable of detecting and distinguishing a myriad of chemicals. Sensory neurons in the olfactory epithelium contain two types of chemosensory G protein-coupled receptors (GPCRs): odorant receptors (ORs), which are encoded by the largest gene family in mammals, and trace amine-associated receptors (TAARs), a smaller family of receptors distantly related to biogenic amine receptors. Do TAARs play a specialized role in olfaction distinct from that of ORs? Genes encoding TAARs are found in diverse vertebrates, from fish to mice to humans. Like OR genes, each Taar gene defines a unique population of canonical sensory neurons dispersed in a single zone of the olfactory epithelium. Ligands for mouse TAARs include a number of volatile amines, several of which are natural constituents of mouse urine, a rich source of rodent social cues. One chemical, 2-phenylethylamine, is reported to be enriched in the urine of stressed animals, and two others, trimethylamine and isoamylamine, are enriched in male versus female urine. Furthermore, isoamylamine has been proposed to be a pheromone that induces puberty acceleration in young female mice. These data raise the possibility that some TAARs are pheromone receptors in the nose, a hypothesis consistent with recent data suggesting that the olfactory epithelium contains dedicated pheromone receptors, separate from pheromone receptors in the vomeronasal organ. Future experiments will clarify the roles of TAARs in olfaction.

  4. Nitric Oxide-Mediated Modulation of Central Network Dynamics during Olfactory Perception

    PubMed Central

    Kobayashi, Suguru; Kitamura, Yoshiichiro; Hamasaki, Yuuta; Saito, Minoru

    2015-01-01

    Nitric oxide (NO) modulates the dynamics of central olfactory networks and has been implicated in olfactory processing including learning. Land mollusks have a specialized olfactory lobe in the brain called the procerebral (PC) lobe. The PC lobe produces ongoing local field potential (LFP) oscillation, which is modulated by olfactory stimulation. We hypothesized that NO should be released in the PC lobe in response to olfactory stimulation, and to prove this, we applied an NO electrode to the PC lobe of the land slug Limax in an isolated tentacle-brain preparation. Olfactory stimulation applied to the olfactory epithelium transiently increased the NO concentration in the PC lobe, and this was blocked by the NO synthase inhibitor L-NAME at 3.7 mM. L-NAME at this concentration did not block the ongoing LFP oscillation, but did block the frequency increase during olfactory stimulation. Olfactory stimulation also enhanced spatial synchronicity of activity, and this response was also blocked by L-NAME. Single electrical stimulation of the superior tentacle nerve (STN) mimicked the effects of olfactory stimulation on LFP frequency and synchronicity, and both of these effects were blocked by L-NAME. L-NAME did not block synaptic transmission from the STN to the nonbursting (NB)-type PC lobe neurons, which presumably produce NO in an activity-dependent manner. Previous behavioral experiments have revealed impairment of olfactory discrimination after L-NAME injection. The recording conditions in the present work likely reproduce the in vivo brain state in those behavioral experiments. We speculate that the dynamical effects of NO released during olfactory perception underlie precise odor representation and memory formation in the brain, presumably through regulation of NB neuron activity. PMID:26360020

  5. Application of the European Test of Olfactory Capabilities in patients with olfactory impairment.

    PubMed

    Joussain, P; Bessy, M; Faure, F; Bellil, D; Landis, B N; Hugentobler, M; Tuorila, H; Mustonen, S; Vento, S I; Delphin-Combe, F; Krolak-Salmon, P; Rouby, C; Bensafi, M

    2016-02-01

    A central issue in olfaction concerns the characterization of loss of olfactory function: partial (hyposmia) or total (anosmia). This paper reports the application in a clinical setting of the European Test of Olfactory Capabilities (ETOC), combining odor detection and identification. The study included three phases. In phase 1, anosmics, hyposmics and controls were tested with the 16-items version of the ETOC. In phase 2, a short version of the ETOC was developed: patients with and controls without olfactory impairment were tested on a 6-items ETOC. In phase 3, to predict olfactory impairments in new individuals, the 16-items ETOC was administered on samples of young and older adults, and the 6-items version was applied in samples of young, elderly participants and Alzheimer patients. In phase 1, linear discriminant analysis (LDA) of ETOC scores classified patients and controls with 87.5 % accuracy. In phase 2, LDA provided 84 % correct classification. Results of phase 3 revealed: (1) 16-items ETOC: whereas in young adults, 10 % were classified as hyposmic and 90 % as normosmic, in elderly, 1 % were classified as anosmic, 39 % hyposmic and 60 % normosmic; (2) 6-items ETOC: 15 % of the young adults were classified as having olfactory impairment, compared to 28 % in the older group and 83 % in Alzheimer patients. In conclusion, the ETOC enables characterizing the prevalence of olfactory impairment in young subjects and in normal and pathological aging. Whereas the 16-items ETOC is more discriminant, the short ETOC may provide a fast (5-10 min) tool to assess olfaction in clinical settings.

  6. Bilateral Synchronous Ectopic Ethmoid Sinus Olfactory Neuroblastoma: A Case Report

    PubMed Central

    Leon-Soriano, Elena; Alfonso, Carolina; Yebenes, Laura; Garcia-Polo, Julio; Lassaletta, Luis; Gavilan, Javier

    2016-01-01

    Patient: Male, 41 Final Diagnosis: Olfactory neuroblastoma Symptoms: Left nasal obstruction • occasional left epistaxis • headache Medication: None Clinical Procedure: Nasal endoscopic examination • neck palpation • CT • bilateral endoscopic resection • MRI • PET-CT • postoperative radiotherapy Specialty: Otolaryngology Objective: Unusual clinical course Background: Olfactory neuroblastoma (ONB), also known as esthesioneuroblastoma, is a rare malignant head and neck cancer thought to originate from the olfactory epithelium. It typically invades contiguous structures at presentation. We report a very rare case of multifocal and ectopic ONB. Case Report: A 41-year-old man presented with left nasal obstruction and occasional left epistaxis associated with headache. Endoscopic examination of the nasal cavities and computed tomography suggested bilateral polypoid masses. Histopathological diagnosis after endoscopic resection established bilateral olfactory neuroblastoma of the ethmoid sinuses. The patient received postoperative radiotherapy. He remains free of disease 4 years after treatment. Conclusions: To the best of our knowledge this is the second documented case of multifocal ectopic olfactory neuroblastoma. Clinicians should consider ONB in the differential diagnosis of bilateral synchronous nasal and paranasal masses to avoid delayed diagnosis. Endoscopic resection of ONB could be an option in selected cases. PMID:27097989

  7. Early olfactory experience induces structural changes in the primary olfactory center of an insect brain.

    PubMed

    Arenas, A; Giurfa, M; Sandoz, J C; Hourcade, B; Devaud, J M; Farina, W M

    2012-03-01

    The antennal lobe (AL) is the first olfactory center of the insect brain and is constituted of different functional units, the glomeruli. In the AL, odors are coded as spatiotemporal patterns of glomerular activity. In honeybees, olfactory learning during early adulthood modifies neural activity in the AL on a long-term scale and also enhances later memory retention. By means of behavioral experiments, we first verified that olfactory learning between the fifth and eighth day of adulthood induces better retention performances at a late adult stage than the same experience acquired before or after this period. We checked that the specificity of memory for the odorants used was improved. We then studied whether such early olfactory learning also induces long-term structural changes in the AL consistent with the formation of long-term olfactory memories. We also measured the volume of 15 identified glomeruli in the ALs of 17-day-old honeybees that either experienced an odor associated with sucrose solution between the fifth and eighth day of adulthood or were left untreated. We found that early olfactory experience induces glomerulus-selective increases in volume that were specific to the learned odor. By comparing our volumetric measures with calcium-imaging recordings from a previous study, performed in 17-day-old bees subjected to the same treatment and experimental conditions, we found that glomeruli that showed structural changes after early learning were those that exhibited a significant increase in neural activity. Our results make evident a correlation between structural and functional changes in the AL following early olfactory learning.

  8. Effects of cadmium on olfactory mediated behaviors and molecular biomarkers in coho salmon (Oncorhynchus kisutch)

    PubMed Central

    Williams, Chase R.; Gallagher, Evan P.

    2013-01-01

    The olfactory system of salmonids is sensitive to the adverse effects of metals such as copper and cadmium. In the current study, we analyzed olfactory-mediated alarm responses, epithelial injury and recovery, and a suite of olfactory molecular biomarkers encoding genes critical in maintaining olfactory function in juvenile coho salmon receiving acute exposures to cadmium (Cd). The molecular biomarkers analyzed included four G-protein coupled receptors (GPCRs) representing the two major classes of odorant receptors (salmon olfactory receptor sorb and vomeronasal receptors svra, svrb, and gpr27), as well as markers of neurite outgrowth (nrn1) and antioxidant responses to metals, including heme oxygenase 1 (hmox1), and peroxiredoxin 1 (prdx1). Coho received acute (8–168 hr) exposures to 3.7 ppb and 347 ppb Cd, and a subset of fish was analyzed following a 16-day depuration. Coho exposed to 347 ppb Cd over 48 hrs exhibited a reduction in freeze responses, and an extensive loss of olfaction accompanied by histological injury to the olfactory epithelium. The olfactory injury in coho exposed to 347 ppb Cd was accompanied at the gene level by significant decreases in expression of the olfactory GPCRs and increased expression of hmox1. Persistent behavioral deficits, histological injury and altered expression of a subset of olfactory biomarkers were still evident in Cd-exposed coho following a 16-day depuration in clean water. Exposure to 3.7 ppb Cd also resulted in reduced freeze responses and histological changes to the olfactory epithelium within 48 hrs of Cd exposure, although the extent of olfactory injury was less severe than observed for fish in the high dose Cd group. Furthermore adverse behavioral effects were present in some coho receiving the low dose of Cd following a 16-day depuration. In summary, acute exposures to environmental levels of Cd can cause olfactory injury in coho salmon that may persist following depuration. Mechanism-based biomarkers of

  9. Lgr5 regulates the regeneration of lesioned nasal respiratory epithelium.

    PubMed

    Zhang, Yan-Qiang; Li, Peng; Zhang, Feng-Qin; Sun, Shao-Jun; Cao, Yin-Guang

    2016-12-09

    Nasal respiratory epithelium is a ciliated pseudostratified columnar epithelium. The cellular components of nasal respiratory epithelium include ciliated cells, goblet cells, and basal cells. Until now, our knowledge in the development of nasal respiratory epithelium is still limited and the cellular mechanism of regeneration is still elusive. In this study, we found that adult stem cell marker leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is expressed in the mice nasal respiratory epithelium. Both immunostaining and lineage tracing analysis indicated Lgr5 positive cells in the nasal respiratory epithelium are proliferative stem/progenitor cells. Using the Rosa-Tdtomato and Rosa26-DTR mice, we elucidated that Lgr5(+) cells participate in the regeneration of lesioned nasal respiratory epithelium, and this group of cells is necessary in the process of epithelium recovery. Using the in vitro culture system, we observed the formation of spheres from Lgr5(+) cells and these spheres have the capacity to generate other types of cells. Above all, this study reported a group of previously unidentified progenitor/stem cells in nasal respiratory epithelium, unveiling the potential cellular mechanism in nasal respiratory epithelium regeneration.

  10. Deletion of Type 3 Adenylyl Cyclase Perturbs the Postnatal Maturation of Olfactory Sensory Neurons and Olfactory Cilium Ultrastructure in Mice

    PubMed Central

    Zhang, Zhe; Yang, Dong; Zhang, Mengdi; Zhu, Ning; Zhou, Yanfen; Storm, Daniel R.; Wang, Zhenshan

    2017-01-01

    Type 3 adenylyl cyclase (Adcy3) is localized to the cilia of olfactory sensory neurons (OSNs) and is an essential component of the olfactory cyclic adenosine monophosphate (cAMP) signaling pathway. Although the role of this enzyme in odor detection and axonal projection in OSNs was previously characterized, researchers will still have to determine its function in the maturation of postnatal OSNs and olfactory cilium ultrastructure. Previous studies on newborns showed that the anatomic structure of the main olfactory epithelium (MOE) of Adcy3 knockout mice (Adcy3-/-) is indistinguishable from that of their wild-type littermates (Adcy3+/+), whereas the architecture and associated composition of MOE are relatively underdeveloped at this early age. The full effects of sensory deprivation on OSNs may not also be exhibited in such age. In the present study, following a comparison of postnatal OSNs in seven-, 30-, and 90-day-old Adcy3-/- mice and wild-type controls (Adcy3+/+), we observed that the absence of Adcy3 leads to cumulative defects in the maturation of OSNs. Upon aging, Adcy3-/- OSNs exhibited increase in immature cells and reduction in mature cells along with elevated apoptosis levels. The density and ultrastructure of Adcy3-/- cilia were also disrupted in mice upon aging. Collectively, our results reveal an indispensable role of Adcy3 in postnatal maturation of OSNs and maintenance of olfactory cilium ultrastructure in mice through adulthood. PMID:28154525

  11. Acetylcholine and Olfactory Perceptual Learning

    ERIC Educational Resources Information Center

    Wilson, Donald A.; Fletcher, Max L.; Sullivan, Regina M.

    2004-01-01

    Olfactory perceptual learning is a relatively long-term, learned increase in perceptual acuity, and has been described in both humans and animals. Data from recent electrophysiological studies have indicated that olfactory perceptual learning may be correlated with changes in odorant receptive fields of neurons in the olfactory bulb and piriform…

  12. Effects of odor stimulation on antidromic spikes in olfactory sensory neurons.

    PubMed

    Scott, John W; Sherrill, Lisa

    2008-12-01

    Spikes were evoked in rat olfactory sensory neuron (OSN) populations by electrical stimulation of the olfactory bulb nerve layer in pentobarbital anesthetized rats. The latencies and recording positions for these compound spikes showed that they originated in olfactory epithelium. Dual simultaneous recordings indicated conduction velocities in the C-fiber range, around 0.5 m/s. These spikes are concluded to arise from antidromically activated olfactory sensory neurons. Electrical stimulation at 5 Hz was used to track changes in the size and latency of the antidromic compound population spike during the odor response. Strong odorant stimuli suppressed the spike size and prolonged its latency. The latency was prolonged throughout long odor stimuli, indicating continued activation of olfactory receptor neuron axons. The amounts of spike suppression and latency change were strongly correlated with the electroolfactogram (EOG) peak size evoked at the same site across odorants and across stimulus intensities. We conclude that the curve of antidromic spike suppression gives a reasonable representation of spiking activity in olfactory sensory neurons driven by odorants and that the correlation of peak spike suppression with the peak EOG shows the accuracy of the EOG as an estimate of intracellular potential in the population of olfactory sensory neurons. In addition, these results have important implications about traffic in olfactory nerve bundles. We did not observe multiple peaks corresponding to stimulated and unstimulated receptor neurons. This suggests synchronization of spikes in olfactory nerve, perhaps by ephaptic interactions. The long-lasting effect on spike latency shows that action potentials continue in the nerve throughout the duration of an odor stimulus in spite of many reports of depolarization block in olfactory receptor neuron cell bodies. Finally, strong odor stimulation caused almost complete block of antidromic spikes. This indicates that a very

  13. Sox10-dependent neural crest origin of olfactory microvillous neurons in zebrafish

    PubMed Central

    Saxena, Ankur; Peng, Brian N; Bronner, Marianne E

    2013-01-01

    The sense of smell in vertebrates is detected by specialized sensory neurons derived from the peripheral nervous system. Classically, it has been presumed that the olfactory placode forms all olfactory sensory neurons. In contrast, we show that the cranial neural crest is the primary source of microvillous sensory neurons within the olfactory epithelium of zebrafish embryos. Using photoconversion-based fate mapping and live cell tracking coupled with laser ablation, we followed neural crest precursors as they migrated from the neural tube to the nasal cavity. A subset that coexpressed Sox10 protein and a neurogenin1 reporter ingressed into the olfactory epithelium and differentiated into microvillous sensory neurons. Timed loss-of-function analysis revealed a critical role for Sox10 in microvillous neurogenesis. Taken together, these findings directly demonstrate a heretofore unknown contribution of the cranial neural crest to olfactory sensory neurons in zebrafish and provide important insights into the assembly of the nascent olfactory system. DOI: http://dx.doi.org/10.7554/eLife.00336.001 PMID:23539289

  14. Changes in Olfactory Receptor Expression Are Correlated With Odor Exposure During Early Development in the zebrafish (Danio rerio).

    PubMed

    Calfún, Cristian; Domínguez, Calixto; Pérez-Acle, Tomás; Whitlock, Kathleen E

    2016-05-01

    We have previously shown that exposure to phenyl ethyl alcohol (PEA) causes an increase in the expression of the transcription factor otx2 in the olfactory epithelium (OE) of juvenile zebrafish, and this change is correlated with the formation of an odor memory of PEA. Here, we show that the changes in otx2 expression are specific to βPEA: exposure to αPEA did not affect otx2 expression. We identified 34 olfactory receptors (ORs) representing 16 families on 4 different chromosomes as candidates for direct regulation of OR expression via Otx2. Subsequent in silico analysis uncovered Hnf3b binding sites closely associated with Otx2 binding sites in the regions flanking the ORs. Analysis by quantitative polymerase chain reaction and RNA-seq of OR expression in developing zebrafish exposed to different isoforms of PEA showed that a subset of ORs containing both Otx2/Hnf3b binding sites were downregulated only in βPEA-exposed juveniles and this change persisted through adult life. Localization of OR expression by in situ hybridization indicates the downregulation occurs at the level of RNA and not the number of cells expressing a given receptor. Finally, analysis of immediate early gene expression in the OE did not reveal changes in c-fos expression in response to either αPEA or βPEA.

  15. Differential response of olfactory sensory neuron populations to copper ion exposure in zebrafish.

    PubMed

    Lazzari, Maurizio; Bettini, Simone; Milani, Liliana; Maurizii, Maria Gabriella; Franceschini, Valeria

    2017-02-01

    The peripheral olfactory system of fish is in direct contact with the external aqueous environment, so dissolved contaminants can easily impair sensory functions and cause neurobehavioral injuries. The olfactory epithelium of fish is arranged in lamellae forming a rosette in the olfactory cavity and contains three main types of olfactory sensory neurons (OSNs): ciliated (cOSNs) and microvillous olfactory sensory neurons (mOSNs), common to all vertebrates, and a third minor group of olfactory neurons, crypt cells, absent in tetrapods. Since copper is a ubiquitously diffusing olfactory toxicant and a spreading contaminant in urban runoff, we investigated the effect of low copper concentration on the three different OSNs in the olfactory epithelium of zebrafish, a model system widely used in biological research. Image analysis was applied for morphometry and quantification of immunohistochemically detected OSNs. Copper exposure resulted in an evident decrease in olfactory epithelium thickness. Moreover, after exposure, the lamellae of the dorsal and ventral halves of the olfactory rosettes showed a different increase in their sensory areas, suggesting a lateral migration of new cells into non-sensory regions. The results of the present study provide clear evidence of a differential response of the three neural cell populations of zebrafish olfactory mucosa after 96h of exposure to copper ions at the sublethal concentration of 30μgL(-1). Densitometric values of cONS, immunostained with anti-G αolf, decreased of about 60% compared to the control. When the fish were transferred to water without copper addition and examined after 3, 10 and 30days, we observed a partial restoration of anti-G αolf staining intensity to normal condition. The recovery of cOSNs appeared sustained by neuronal proliferation, quantified with anti-PCNA immunostaining, in particular in the early days after exposure. The densitometric analysis applied to mOSNs, immunostained with anti-TRPC2

  16. Acute sodium tungstate inhalation is associated with minimal olfactory transport of tungsten (188W) to the rat brain.

    PubMed

    Radcliffe, Pheona M; Olabisi, Ayodele O; Wagner, Dean J; Leavens, Teresa; Wong, Brian A; Struve, Melanie F; Chapman, Gail D; Wilfong, Erin R; Dorman, David C

    2009-05-01

    Olfactory transport of represents an important mechanism for direct delivery of certain metals to the central nervous system (CNS). The objective of this study was to determine whether inhaled tungsten (W) undergoes olfactory uptake and transport to the rat brain. Male, 16-week-old, Sprague-Dawley rats underwent a single, 90-min, nose-only exposure to a Na(2)(188)WO(4) aerosol (256 mg W/m(3)). Rats had the right nostril plugged to prevent nasal deposition of (188)W on the occluded side. The left and right sides of the nose and brain, including the olfactory pathway and striatum, were sampled at 0, 1, 3, 7, and 21 days post-exposure. Gamma spectrometry (n=7 rats/time point) was used to compare the levels of (188)W found on the left and right sides of the nose and brain and blood to determine the contribution of olfactory uptake to brain (188)W levels. Respiratory and olfactory epithelial samples from the side with the occluded nostril had significantly lower end-of-exposure (188)W levels confirming the occlusion procedure. Olfactory bulb, olfactory tract/tubercle, striatum, cerebellum, rest of brain (188)W levels paralleled blood (188)W concentrations at approximately 2-3% of measured blood levels. Brain (188)W concentrations were highest immediately following exposure, and returned to near background concentrations within 3 days. A statistically significant difference in olfactory bulb (188)W concentration was seen at 3 days post-exposure. At this time, (188)W concentrations in the olfactory bulb from the side ipsilateral to the unoccluded nostril were approximately 4-fold higher than those seen in the contralateral olfactory bulb. Our data suggest that the concentration of (188)W in the olfactory bulb remained low throughout the experiment, i.e., approximately 1-3% of the amount of tungsten seen in the olfactory epithelium suggesting that olfactory transport plays a minimal role in delivering tungsten to the rat brain.

  17. Amino Acid- vs. Peptide-Odorants: Responses of Individual Olfactory Receptor Neurons in an Aquatic Species

    PubMed Central

    Hassenklöver, Thomas; Pallesen, Lars P.; Schild, Detlev; Manzini, Ivan

    2012-01-01

    Amino acids are widely used waterborne olfactory stimuli proposed to serve as cues in the search for food. In natural waters the main source of amino acids is the decomposition of proteins. But this process also produces a variety of small peptides as intermediate cleavage products. In the present study we tested whether amino acids actually are the natural and adequate stimuli for the olfactory receptors they bind to. Alternatively, these olfactory receptors could be peptide receptors which also bind amino acids though at lower affinity. Employing calcium imaging in acute slices of the main olfactory epithelium of the fully aquatic larvae of Xenopus laevis we show that amino acids, and not peptides, are more effective waterborne odorants. PMID:23300867

  18. Human olfactory neurons respond to odor stimuli with an increase in cytoplasmic Ca2+.

    PubMed Central

    Restrepo, D; Okada, Y; Teeter, J H; Lowry, L D; Cowart, B; Brand, J G

    1993-01-01

    The sense of smell allows terrestrial animals to collect information about the chemical nature of their environment through the detection of airborne molecules. In humans smell is believed to play an important role in protecting the organism from environmental hazards such as fire, gas leaks and spoiled food, in determining the flavor of foods, and perhaps in infant-parent bonding. In addition, the study of human olfaction is relevant to a number of medical problems that result in olfactory dysfunction, which can affect nutritional state, and to the study of the etiology of neurodegenerative diseases which manifest themselves in the olfactory epithelium. Although much is known about behavioral aspects of human olfaction, little is understood about the underlying cellular mechanisms in humans. Here we report that viable human olfactory neurons (HON) can be isolated from olfactory tissue biopsies, and we find that HON respond to odorants with an increase in intracellular calcium concentration ([Cai]). Images FIGURE 2 PMID:8369416

  19. Expression and function of the empty spiracles gene in olfactory sense organ development of Drosophila melanogaster.

    PubMed

    Sen, Sonia; Hartmann, Beate; Reichert, Heinrich; Rodrigues, Veronica

    2010-11-01

    In Drosophila, the cephalic gap gene empty spiracles plays key roles in embryonic patterning of the peripheral and central nervous system. During postembryonic development, it is involved in the development of central olfactory circuitry in the antennal lobe of the adult. However, its possible role in the postembryonic development of peripheral olfactory sense organs has not been investigated. Here, we show that empty spiracles acts in a subset of precursors that generate the olfactory sense organs of the adult antenna. All empty spiracles-expressing precursor cells co-express the proneural gene amos and the early patterning gene lozenge. Moreover, the expression of empty spiracles in these precursor cells is dependent on both amos and lozenge. Functional analysis reveals two distinct roles of empty spiracles in the development of olfactory sense organs. Genetic interaction studies in a lozenge-sensitized background uncover a requirement of empty spiracles in the formation of trichoid and basiconic olfactory sensilla. MARCM-based clonal mutant analysis reveals an additional role during axonal targeting of olfactory sensory neurons to glomeruli within the antennal lobe. Our findings on empty spiracles action in olfactory sense organ development complement previous studies that demonstrate its requirement in olfactory interneurons and, taken together with studies on the murine homologs of empty spiracles, suggest that conserved molecular genetic programs might be responsible for the formation of both peripheral and central olfactory circuitry in insects and mammals.

  20. Properties and mechanisms of olfactory learning and memory.

    PubMed

    Tong, Michelle T; Peace, Shane T; Cleland, Thomas A

    2014-01-01

    Memories are dynamic physical phenomena with psychometric forms as well as characteristic timescales. Most of our understanding of the cellular mechanisms underlying the neurophysiology of memory, however, derives from one-trial learning paradigms that, while powerful, do not fully embody the gradual, representational, and statistical aspects of cumulative learning. The early olfactory system-particularly olfactory bulb-comprises a reasonably well-understood and experimentally accessible neuronal network with intrinsic plasticity that underlies both one-trial (adult aversive, neonatal) and cumulative (adult appetitive) odor learning. These olfactory circuits employ many of the same molecular and structural mechanisms of memory as, for example, hippocampal circuits following inhibitory avoidance conditioning, but the temporal sequences of post-conditioning molecular events are likely to differ owing to the need to incorporate new information from ongoing learning events into the evolving memory trace. Moreover, the shapes of acquired odor representations, and their gradual transformation over the course of cumulative learning, also can be directly measured, adding an additional representational dimension to the traditional metrics of memory strength and persistence. In this review, we describe some established molecular and structural mechanisms of memory with a focus on the timecourses of post-conditioning molecular processes. We describe the properties of odor learning intrinsic to the olfactory bulb and review the utility of the olfactory system of adult rodents as a memory system in which to study the cellular mechanisms of cumulative learning.

  1. From chemical neuroanatomy to an understanding of the olfactory system.

    PubMed

    Oboti, L; Peretto, P; Marchis, S De; Fasolo, A

    2011-10-19

    The olfactory system is the appropriate model for studying several aspects of neuronal physiology spanning from the developmental stage to neural network remodelling in the adult brain. Both the morphological and physiological understanding of this system were strongly supported by classical histochemistry. It is emblematic the case of the Olfactory Marker Protein (OMP) staining, the first, powerful marker for fully differentiated olfactory receptor neurons and a key tool to investigate the dynamic relations between peripheral sensory epithelia and central relay regions given its presence within olfactory fibers reaching the olfactory bulb (OB). Similarly, the use of thymidine analogues was able to show neurogenesis in an adult mammalian brain far before modern virus labelling and lipophilic tracers based methods. Nowadays, a wealth of new histochemical techniques combining cell and molecular biology approaches is available, giving stance to move from the analysis of the chemically identified circuitries to functional research. The study of adult neurogenesis is indeed one of the best explanatory examples of this statement. After defining the cell types involved and the basic physiology of this phenomenon in the OB plasticity, we can now analyze the role of neurogenesis in well testable behaviours related to socio-chemical communication in rodents.

  2. An arterially perfused nose-olfactory bulb preparation of the rat.

    PubMed

    Pérez de los Cobos Pallarés, Fernando; Stanić, Davor; Farmer, David; Dutschmann, Mathias; Egger, Veronica

    2015-09-01

    A main feature of the mammalian olfactory bulb network is the presence of various rhythmic activities, in particular, gamma, beta, and theta oscillations, with the latter coupled to the respiratory rhythm. Interactions between those oscillations as well as the spatial distribution of network activation are likely to determine olfactory coding. Here, we describe a novel semi-intact perfused nose-olfactory bulb-brain stem preparation in rats with both a preserved olfactory epithelium and brain stem, which could be particularly suitable for the study of oscillatory activity and spatial odor mapping within the olfactory bulb, in particular, in hitherto inaccessible locations. In the perfused olfactory bulb, we observed robust spontaneous oscillations, mostly in the theta range. Odor application resulted in an increase in oscillatory power in higher frequency ranges, stimulus-locked local field potentials, and excitation or inhibition of individual bulbar neurons, similar to odor responses reported from in vivo recordings. Thus our method constitutes the first viable in situ preparation of a mammalian system that uses airborne odor stimuli and preserves these characteristic features of odor processing. This preparation will allow the use of highly invasive experimental procedures and the application of techniques such as patch-clamp recording, high-resolution imaging, and optogenetics within the entire olfactory bulb.

  3. Olf-1-binding site: characterization of an olfactory neuron-specific promoter motif.

    PubMed Central

    Kudrycki, K; Stein-Izsak, C; Behn, C; Grillo, M; Akeson, R; Margolis, F L

    1993-01-01

    We report characterization of several domains within the 5' flanking region of the olfactory marker protein (OMP) gene that may participate in regulating transcription of this and other olfactory neuron-specific genes. Analysis by electrophoretic mobility shift assay and DNase I footprinting identifies two regions that contain a novel sequence motif. Interactions between this motif and nuclear proteins were detected only with nuclear protein extracts derived from olfactory neuroepithelium, and this activity is more abundant in olfactory epithelium enriched in immature neurons. We have designated a factor(s) involved in this binding as Olf-1. The Olf-1-binding motif consensus sequence was defined as TCCCC(A/T)NGGAG. Studies with transgenic mice indicate that a 0.3-kb fragment of the OMP gene containing one Olf-1 motif is sufficient for olfactory tissue-specific expression of the reporter gene. Some of the other identified sequence motifs also interact specifically with olfactory nuclear protein extracts. We propose that Olf-1 is a novel, olfactory neuron-specific trans-acting factor involved in the cell-specific expression of OMP. Images PMID:8474458

  4. Odor Memory Stability after Reinnervation of the Olfactory Bulb

    PubMed Central

    Blanco-Hernández, Eduardo; Valle-Leija, Pablo; Zomosa-Signoret, Viviana; Drucker-Colín, René; Vidaltamayo, Román

    2012-01-01

    The olfactory system, particularly the olfactory epithelium, presents a unique opportunity to study the regenerative capabilities of the brain, because of its ability to recover after damage. In this study, we ablated olfactory sensory neurons with methimazole and followed the anatomical and functional recovery of circuits expressing genetic markers for I7 and M72 receptors (M72-IRES-tau-LacZ and I7-IRES-tau-GFP). Our results show that 45 days after methimazole-induced lesion, axonal projections to the bulb of M72 and I7 populations are largely reestablished. Furthermore, regenerated glomeruli are re-formed within the same areas as those of control, unexposed mice. This anatomical regeneration correlates with functional recovery of a previously learned odorant-discrimination task, dependent on the cognate ligands for M72 and I7. Following regeneration, mice also recover innate responsiveness to TMT and urine. Our findings show that regeneration of neuronal circuits in the olfactory system can be achieved with remarkable precision and underscore the importance of glomerular organization to evoke memory traces stored in the brain. PMID:23071557

  5. The Beneficial Impact of Antidepressant Drugs on Prenatal Stress-Evoked Malfunction of the Insulin-Like Growth Factor-1 (IGF-1) Protein Family in the Olfactory Bulbs of Adult Rats.

    PubMed

    Trojan, Ewa; Głombik, Katarzyna; Ślusarczyk, Joanna; Budziszewska, Bogusława; Kubera, Marta; Roman, Adam; Lasoń, Władysław; Basta-Kaim, Agnieszka

    2016-02-01

    Insulin-like growth factor-1 (IGF-1) promotes the growth, differentiation, and survival of both neurons and glial cells, and it is believed to exert antidepressant-like activity. Thus, disturbances in the IGF-1 system could be responsible for the course of depression. To date, there have been no papers showing the impact of chronic antidepressant treatment on the IGF-1 network in the olfactory bulb (OB) in an animal model of depression. Prenatal stress was used as model of depression. Twenty-four 3-month-old male offspring of control and stressed mothers were subjected to behavioral testing (forced swim test). The mRNA expression of IGF-1 and IGF-1 receptor (IGF-1R) and the protein level of IGF-1 and its phosphorylation, as well as the concentrations of IGF-binding proteins (IGFBP-2, -4, -3, and -6), were measured in OBs before and after chronic imipramine, fluoxetine, or tianeptine administration. Adult rats exposed prenatally to stressful stimuli displayed not only depression-like behavior but also decreased IGF-1 expression, dysregulation in the IGFBP network, and diminished mRNA expression, as well as IGF-1R phosphorylation, in the OB. The administration of antidepressants normalized most of the changes in the IGF-1 system of the OB evoked by prenatal stress. These results suggested a beneficial effect of chronic antidepressant drug treatment in the alleviation of IGF-1 family malfunction in OBs in an animal model of depression.

  6. Primary Events in Olfactory Reception

    DTIC Science & Technology

    1993-01-08

    sustentacular cells and Bowman’s glands and that it is deposited in the lower mucus layer of olfactory neuroepithelium. Next, we extracted mRNA from...protrude from the dendritic tips of olfactory receptor neurons. These cilia are surrounded by a layer of mucus that lines the olfactory...neuroepithelium. Odorants that enter the nasal cavity with the inspired air partition into and diffuse through this aqueous mucus layer on their way to odorant

  7. An Epigenetic Signature for Monoallelic Olfactory Receptor Expression

    PubMed Central

    Magklara, Angeliki; Yen, Angela; Colquitt, Bradley M.; Clowney, E. Josephine; Allen, William; Markenscoff-Papadimitriou, Eirene; Evans, Zoe A.; Kheradpour, Pouya; Mountoufaris, George; Carey, Catriona; Barnea, Gilad; Kellis, Manolis; Lomvardas, Stavros

    2011-01-01

    SUMMARY Constitutive heterochromatin is traditionally viewed as the static form of heterochromatin that silences pericentromeric and telomeric repeats in a cell cycle and differentiation independent manner. Here, we show that in the mouse olfactory epithelium, olfactory receptor (OR) genes are marked, in a highly dynamic fashion, with the molecular hallmarks of constitutive heterochromatin, H3K9me3 and H4K20me3. The cell-type and developmentally dependent deposition of these marks along the OR clusters is, most likely, reversed during the process of OR choice to allow for monogenic and monoallelic OR expression. In contrast to the current view of OR choice, our data suggest that OR silencing takes place before OR expression, indicating that it is not the product of an OR-elicited feedback signal. This suggests a new role for chromatin-mediated silencing as the molecular foundation upon which singular and stochastic selection can be applied. PMID:21529909

  8. A Renal Olfactory Receptor Aids in Kidney Glucose Handling

    PubMed Central

    Shepard, Blythe D.; Cheval, Lydie; Peterlin, Zita; Firestein, Stuart; Koepsell, Hermann; Doucet, Alain; Pluznick, Jennifer L.

    2016-01-01

    Olfactory receptors (ORs) are G protein-coupled receptors which serve important sensory functions beyond their role as odorant detectors in the olfactory epithelium. Here we describe a novel role for one of these ORs, Olfr1393, as a regulator of renal glucose handling. Olfr1393 is specifically expressed in the kidney proximal tubule, which is the site of renal glucose reabsorption. Olfr1393 knockout mice exhibit urinary glucose wasting and improved glucose tolerance, despite euglycemia and normal insulin levels. Consistent with this phenotype, Olfr1393 knockout mice have a significant decrease in luminal expression of Sglt1, a key renal glucose transporter, uncovering a novel regulatory pathway involving Olfr1393 and Sglt1. In addition, by utilizing a large scale screen of over 1400 chemicals we reveal the ligand profile of Olfr1393 for the first time, offering new insight into potential pathways of physiological regulation for this novel signaling pathway. PMID:27739476

  9. Development of the olfactory pathways in platypus and echidna.

    PubMed

    Ashwell, Ken W S

    2012-01-01

    The two groups of living monotremes (platypus and echidnas) have remarkably different olfactory structures in the adult. The layers of the main olfactory bulb of the short-beaked echidna are extensively folded, whereas those of the platypus are not. Similarly, the surface area of the piriform cortex of the echidna is large and its lamination complex, whereas in the platypus it is small and simple. It has been argued that the modern echidnas are derived from a platypus-like ancestor, in which case the extensive olfactory specializations of the modern echidnas would have developed relatively recently in monotreme evolution. In this study, the development of the constituent structures of the olfactory pathway was studied in sectioned platypus and echidna embryos and post-hatchlings at the Museum für Naturkunde, Berlin, Germany. The aim was to determine whether the olfactory structures follow a similar maturational path in the two monotremes during embryonic and early post-hatching ages or whether they show very different developmental paths from the outset. The findings indicate that anatomical differences in the central olfactory system between the short-beaked echidna and the platypus begin to develop immediately before hatching, although details of differences in nasal cavity architecture emerge progressively during late post-hatching life. These findings are most consistent with the proposition that the two modern monotreme lineages have followed independent evolutionary paths from a less olfaction-specialized ancestor. The monotreme olfactory pathway does not appear to be sufficiently structurally mature at birth to allow olfaction-mediated behaviour, because central components of both the main and accessory olfactory system have not differentiated at the time of hatching.

  10. Recent Trend in Development of Olfactory Displays

    NASA Astrophysics Data System (ADS)

    Yanagida, Yasuyuki

    An olfactory display is a device that generates scented air with desired concentration of aroma, and delivers it to the user's olfactory organ. In this article, the nature of olfaction is briefly described from the view point of how to configure olfactory displays. Next, component technologies to compose olfactory displays, i.e., making scents and delivering scents, are categorized. Several existing olfactory display systems are introduced to show the current status of research and development of olfactory displays.

  11. Distribution of carnosine-like peptides in the nervous system of developing and adult zebrafish (Danio rerio) and embryonic effects of chronic carnosine exposure

    PubMed Central

    Azher, Seema; Margolis, Frank L.; Patel, Kamakshi; Mousa, Ahmad; Majid, Arshad

    2013-01-01

    Carnosine-like peptides (carnosine-LP) are a family of histidine derivatives that are present in the nervous system of various species and that exhibit antioxidant, anti-matrix-metalloproteinase, anti-excitotoxic, and free-radical scavenging properties. They are also neuroprotective in animal models of cerebral ischemia. Although the function of carnosine-LP is largely unknown, the hypothesis has been advanced that they play a role in the developing nervous system. Since the zebrafish is an excellent vertebrate model for studying development and disease, we have examined the distribution pattern of carnosine-LP in the adult and developing zebrafish. In the adult, immunoreactivity for carnosine-LP is specifically concentrated in sensory neurons and non-sensory cells of the olfactory epithelium, the olfactory nerve, and the olfactory bulb. Robust staining has also been observed in the retinal outer nuclear layer and the corneal epithelium. Developmental studies have revealed immunostaining for carnosine-LP as early as 18 h, 24 h, and 7 days post-fertilization in, respectively, the olfactory, corneal, and retinal primordia. These data suggest that carnosine-LP are involved in olfactory and visual function. We have also investigated the effects of chronic (7 days) exposure to carnosine on embryonic development and show that 0.01 μM to 10 mM concentrations of carnosine do not elicit significant deleterious effects. Conversely, treatment with 100 mM carnosine results in developmental delay and compromised larval survival. These results indicate that, at lower concentrations, exogenously administered carnosine can be used to explore the role of carnosine in development and developmental disorders of the nervous system. PMID:19440736

  12. Recovery of olfactory function after bilateral bulbectomy.

    PubMed

    Wright, J W; Harding, J W

    1982-04-16

    Mice were trained to discriminate between scented and unscented air. After olfactory bulbs were removed, discrimination was lost, but returned with the formation of synaptic connections between regenerated primary olfactory neurons and the cortex of the forebrain. The acquisition of a second olfactory-mediated task by long-term bulbectomized mice and controls was indistinguishable. The results emphasize the plasticity of the nervous system, correlate the presence of neural connections between olfactory mucosa and forebrain with the recovery of olfactory function, suggest that olfactory-mediated memory resides at least in part outside the olfactory bulbs, and demonstrate that the bulbs are not required for the acquisition of olfactory tasks.

  13. Olfactory short-term memory encoding and maintenance - an event-related potential study.

    PubMed

    Lenk, Steffen; Bluschke, Annet; Beste, Christian; Iannilli, Emilia; Rößner, Veit; Hummel, Thomas; Bender, Stephan

    2014-09-01

    This study examined whether the memory encoding and short term maintenance of olfactory stimuli is associated with neurophysiological activation patterns which parallel those described for sensory modalities such as vision and auditory. We examined olfactory event-related potentials in an olfactory change detection task in twenty-four healthy adults and compared the measured activation to that found during passive olfactory stimulation. During the early olfactory post-processing phase, we found a sustained negativity over bilateral frontotemporal areas in the passive perception condition which was enhanced in the active memory task. There was no significant lateralization in either experimental condition. During the maintenance interval at the end of the delay period, we still found sustained activation over bilateral frontotemporal areas which was more negative in trials with correct - as compared to incorrect - behavioural responses. This was complemented by a general significantly stronger frontocentral activation. Summarizing, we were able to show that olfactory short term memory involves a parallel sequence of activation as found in other sensory modalities. In addition to olfactory-specific frontotemporal activations in the memory encoding phase, we found slow cortical potentials over frontocentral areas during the memory maintenance phase indicating the activation of a supramodal memory maintenance system. These findings could represent the neurophysiological underpinning of the 'olfactory flacon', the olfactory counter-part to the visual sketchpad and phonological loop embedded in Baddeley's working memory model.

  14. Enhanced trapping of stable flies via olfactory and visual cues

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adult stable flies are highly attracted to the so-called Alsynite cylinder trap; however this trap is expensive. Here we report the development of a cheaper and better white panel trap with options of adding visual and olfactory stimuli for enhanced stable fly trapping. The white panel trap attracte...

  15. Olfactory Stimuli Increase Presence in Virtual Environments

    PubMed Central

    Munyan, Benson G.; Neer, Sandra M.; Beidel, Deborah C.; Jentsch, Florian

    2016-01-01

    Background Exposure therapy (EXP) is the most empirically supported treatment for anxiety and trauma-related disorders. EXP consists of repeated exposure to a feared object or situation in the absence of the feared outcome in order to extinguish associated anxiety. Key to the success of EXP is the need to present the feared object/event/situation in as much detail and utilizing as many sensory modalities as possible, in order to augment the sense of presence during exposure sessions. Various technologies used to augment the exposure therapy process by presenting multi-sensory cues (e.g., sights, smells, sounds). Studies have shown that scents can elicit emotionally charged memories, but no prior research has examined the effect of olfactory stimuli upon the patient’s sense of presence during simulated exposure tasks. Methods 60 adult participants navigated a mildly anxiety-producing virtual environment (VE) similar to those used in the treatment of anxiety disorders. Participants had no autobiographical memory associated with the VE. State anxiety, Presence ratings, and electrodermal (EDA) activity were collected throughout the experiment. Results Utilizing a Bonferroni corrected Linear Mixed Model, our results showed statistically significant relationships between olfactory stimuli and presence as assessed by both the Igroup Presence Questionnaire (IPQ: R2 = 0.85, (F(3,52) = 6.625, p = 0.0007) and a single item visual-analogue scale (R2 = 0.85, (F(3,52) = 5.382, p = 0.0027). State anxiety was unaffected by the presence or absence of olfactory cues. EDA was unaffected by experimental condition. Conclusion Olfactory stimuli increase presence in virtual environments that approximate those typical in exposure therapy, but did not increase EDA. Additionally, once administered, the removal of scents resulted in a disproportionate decrease in presence. Implications for incorporating the use of scents to increase the efficacy of exposure therapy is discussed. PMID

  16. Olfactory illusions: where are they?

    PubMed

    Stevenson, Richard J

    2011-12-01

    It has been suggested that there maybe no olfactory illusions. This manuscript examines this claim and argues that it arises because olfactory illusions are not typically accompanied by an awareness of their illusory nature. To demonstrate that olfactory illusions do occur, the relevant empirical literature is reviewed, by examining instances of where the same stimulus results in different percepts, and of where different stimuli result in the same percept. The final part of the manuscript evaluates the evidence favoring the existence of olfactory illusions, and then examines why they may not typically be accompanied by awareness. Three contributory mechanisms are discussed, relating to difficulty of verification and paucity of olfactory knowledge, the role of change blindness, and restricted access consciousness in this sense.

  17. Zebrafish olfactory receptor ORA1 recognizes a putative reproductive pheromone

    PubMed Central

    Ahuja, Gaurav; Korsching, Sigrun

    2014-01-01

    Teleost v1r-related ora genes constitute a small and highly conserved olfactory receptor gene family, and their direct orthologs are present in lineages as distant as cartilaginous fishes. Recently, the first member of the ora gene family was deorphanized. ORA1 detects p-hydroxyphenylacetic acid with high sensitivity and specificity. This compound elicits olfactory-mediated oviposition behavior in adult zebrafish mating pairs, suggesting a potential function as a reproductive pheromone for pHPAA itself or a related substance. This association of an odor and its cognate receptor with an oviposition response may provide a molecular basis for studying neural circuits involved in fish reproduction. PMID:26842458

  18. Noradrenergic and cholinergic modulation of olfactory bulb sensory processing

    PubMed Central

    Devore, Sasha; Linster, Christiane

    2012-01-01

    Neuromodulation in sensory perception serves important functions such as regulation of signal to noise ratio, attention, and modulation of learning and memory. Neuromodulators in specific sensory areas often have highly similar cellular, but distinct behavioral effects. To address this issue, we here review the function and role of two neuromodulators, acetylcholine (Ach) and noradrenaline (NE) for olfactory sensory processing in the adult main olfactory bulb. We first describe specific bulbar sensory computations, review cellular effects of each modulator and then address their specific roles in bulbar sensory processing. We finally put these data in a behavioral and computational perspective. PMID:22905025

  19. [Neutrophils and monocytes in gingival epithelium

    PubMed

    Meng, H X; Zheng, L P

    1994-06-01

    Neutrophils and monocytes of gingival epithellium in health gingiva(H),marginal gingivitis(MG),juvenile periodontitis(JP),adult periodontitis(AP) and subgingival bacteria were quantitated and analyzed,The results showed that the numbers of PMN within either pocket epithelium or oral gingival epithelium in JP were significantly lower than in AP and G.The amounts of PMN in AP were much larger than other three groups.Positive correlation between the number of PMN in sulcular pocket epitelium and the motile bacteri of subgingival plaque was demonstrated by correlation analysis.Monocytes mainly presented in deep pocket and junctional epithelum which were stained by NAE method,however very few Langhans cells were seen in these areas.

  20. Viral disruption of olfactory progenitors is exacerbated in allergic mice.

    PubMed

    Ueha, R; Mukherjee, S; Ueha, S; de Almeida Nagata, D E; Sakamoto, T; Kondo, K; Yamasoba, T; Lukacs, N W; Kunkel, S L

    2014-09-01

    Upper airway viral infection in patients with airway allergy often exacerbates olfactory dysfunction, but the mechanism for this exacerbation remains unclear. Here, we examined the effects of respiratory syncytial virus (RSV) infection, in the presence or absence of airway allergy, on olfactory receptor neurons (ORNs) and their progenitors in mice. Immunohistological analyses revealed that cockroach allergen (CRA)-induced airway allergy alone did not affect the number of OMP(+) mature ORNs and SOX2(+) ORN progenitors. Intranasal RSV line 19 infection in allergy-free mice resulted in a transient decrease in SOX2(+) ORN progenitors without affecting OMP(+) ORNs. In contrast, the RSV-induced decrease in SOX2(+) ORN progenitors was exacerbated and prolonged in allergic mice, which resulted in eventual loss of OMP(+) ORNs. In the allergic mice, reduction of RSV in the olfactory epithelium was delayed as compared with allergy-free mice. These results suggest that ORN progenitors were impaired by RSV infection and that airway allergy exacerbated damage to ORN progenitors by reducing viral clearance.

  1. Study of the morphology of the olfactory organ of African ostrich chick.

    PubMed

    Jin, E H; Peng, K M; Wang, J A X; Du, A N; Tang, L; Wei, L; Wang, Y; Li, S H; Song, H

    2008-06-01

    The anatomy and histology of the olfactory organ of African ostrich chick were carefully observed by gross anatomy observation, paraffin sectioning and haematoxylin-eosin (HE) staining. The results showed that there were no keratotic nose lids at the entrance of the external naris, and that the nasal cavity was separated into two imperforate compartments by the nasal septum. The posterior conchae were connected with the middle conchae without cohering to nasal walls, and appeared to be part of a palinal elongation of the middle conchae. Olfactory cells were distributed in the mucosal epithelium of middle and posterior conchae. Nasal glands were shaped like irregular rectangles, and their connective tissue extended to the parenchyma, which was divided into many glandular lobules. The layers of the olfactory bulb were indistinct, the globular structure was inconspicuous and the granular cells were scattered relatively in the lamina granularis externa.

  2. Origin, migration and fate of newly generated neurons in the adult rodent piriform cortex.

    PubMed

    Shapiro, Lee A; Ng, Kwan L; Kinyamu, Richard; Whitaker-Azmitia, Patricia; Geisert, Eldon E; Blurton-Jones, Mathew; Zhou, Qun-Yong; Ribak, Charles E

    2007-09-01

    Newly generated neurons are continuously added to the olfactory epithelium and olfactory bulbs of adult mammals. Studies also report newly generated neurons in the piriform cortex, the primary cortical projection site of the olfactory bulbs. The current study used BrdU-injection paradigms, and in vivo and in vitro DiI tracing methods to address three fundamental issues of these cells: their origin, migratory route and fate. The results show that 1 day after a BrdU-injection, BrdU/DCX double-labeled cells appear deep to the ventricular subependyma, within the white matter. Such cells appear further ventral and caudal in the ensuing days, first appearing in the rostral piriform cortex of mice at 2 days after the BrdU-injection, and at 4 days in the rat. In the caudal piriform cortex, BrdU/DCX labeled cells first appear at 4 days after the injection in mice and 7 days in rats. The time it takes for these cells to appear in the piriform cortex and the temporal distribution pattern suggest that they migrate from outside this region. DiI tracing methods confirmed a migratory route to the piriform cortex from the ventricular subependyma. The presence of BrdU/NeuN labeled cells as early as 7 days after a BrdU injection in mice and 10 days in the rat and lasting as long as 41 days indicates that some of these cells have extended survival durations in the adult piriform cortex.

  3. Detection of human cytomegalovirus in normal and neoplastic breast epithelium

    PubMed Central

    2010-01-01

    Introduction Human cytomegalovirus (HCMV) establishes a persistent life-long infection, and can cause severe pathology in the fetus and the immunocompromised host[1]. Breast milk is the primary route of transmission in humans worldwide, and breast epithelium is thus a likely site of persistent infection and/or reactivation, though this phenomenon has not previously been demonstrated. Increasing evidence indicates HCMV infection can modulate signaling pathways associated with oncogenesis. We hypothesized that persistent HCMV infection occurs in normal adult breast epithelium and that persistent viral expression might be associated with normal and neoplastic ductal epithelium. Methods Surgical biopsy specimens of normal breast (n = 38) breast carcinoma (n = 39) and paired normal breast from breast cancer patients (n = 21) were obtained. Specimens were evaluated by immunohistochemistry, in situ hybridization, PCR and DNA sequencing for evidence of HCMV antigens and nucleic acids. Results We detected HCMV expression specifically in glandular epithelium in 17/27 (63%) of normal adult breast cases evaluated. In contrast, HCMV expression was evident in the neoplastic epithelium of 31/32 (97%) patients with ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) cases evaluated (p = 0.0009). Conclusions These findings are the first to demonstrate that persistent HCMV infection occurs in breast epithelium in a significant percentage of normal adult females. HCMV expression was also evident in neoplastic breast epithelium in a high percentage of normal and neoplastic breast tissues obtained from breast cancer patients, raising the possibility that viral infection may be involved in the neoplastic process. PMID:21429243

  4. The sense of smell, its signalling pathways, and the dichotomy of cilia and microvilli in olfactory sensory cells

    PubMed Central

    2007-01-01

    Smell is often regarded as an ancillary perception in primates, who seem so dominated by their sense of vision. In this paper, we will portray some aspects of the significance of olfaction to human life and speculate on what evolutionary factors contribute to keeping it alive. We then outline the functional architecture of olfactory sensory neurons and their signal transduction pathways, which are the primary detectors that render olfactory perception possible. Throughout the phylogenetic tree, olfactory neurons, at their apical tip, are either decorated with cilia or with microvilli. The significance of this dichotomy is unknown. It is generally assumed that mammalian olfactory neurons are of the ciliary type only. The existance of so-called olfactory microvillar cells in mammals, however, is well documented, but their nature remains unclear and their function orphaned. This paper discusses the possibility, that in the main olfactory epithelium of mammals ciliated and microvillar sensory cells exist concurrently. We review evidence related to this hypothesis and ask, what function olfactory microvillar cells might have and what signalling mechanisms they use. PMID:17903277

  5. Segregated pathways to the vomeronasal amygdala: differential projections from the anterior and posterior divisions of the accessory olfactory bulb.

    PubMed

    Mohedano-Moriano, Alicia; Pro-Sistiaga, Palma; Ubeda-Bañón, Isabel; Crespo, Carlos; Insausti, Ricardo; Martinez-Marcos, Alino

    2007-04-01

    Apically and basally located receptor neurons in the vomeronasal sensory epithelium express G(i2 alpha)- and G(o alpha)-proteins, V1R and V2R vomeronasal receptors, project to the anterior and posterior accessory olfactory bulb and respond to different stimuli, respectively. The extent to which secondary projections from the two portions of the accessory olfactory bulb are convergent in the vomeronasal amygdala is controversial. This issue is addressed by using anterograde and retrograde tract-tracing methods in rats including electron microscopy. Injections of dextran-amines, Fluoro Gold, cholera toxin-B subunit and Fast Blue were delivered to the anterior and posterior accessory olfactory bulb, bed nucleus of the stria terminalis, dorsal anterior amygdala and bed nucleus of the accessory olfactory tract/anteroventral medial amygdaloid nucleus. We have demonstrated that, apart from common vomeronasal-recipient areas, only the anterior accessory olfactory bulb projects to the bed nucleus of the stria terminalis, medial division, posteromedial part, and only the posterior accessory olfactory bulb projects to the dorsal anterior amygdala and deep cell layers of the bed nucleus of the accessory olfactory tract and the anteroventral medial amygdaloid nucleus. These results provide evidence that, excluding areas of convergence, the V1R and V2R vomeronasal pathways project to specific areas of the amygdala. These two vomeronasal subsystems are therefore anatomically and functionally separated in the telencephalon.

  6. Olfactory dysfunction in Parkinson's disease.

    PubMed Central

    Hawkes, C H; Shephard, B C; Daniel, S E

    1997-01-01

    OBJECTIVE: To evaluate olfactory function in Parkinson's disease. METHODS: A standardised odour identification test was used, together with an evoked potential assessment with hydrogen sulphide. In addition, histological analysis was performed on the olfactory bulbs of cadavers who died from Parkinson's disease. RESULTS: Over 70% of patients studied (71 of 96) were outside the 95% limit of normal on the identification test in an age matched sample and there was an unusual pattern of selective loss to certain odours, not hitherto described. The evoked potentials were significantly delayed but of comparable amplitude to a control matched population. Of the 73 patients studied only 37 had a technically satisfactory record containing a clear response to both gases and of these, 12 were delayed. For H2S there was more delay on stimulating the right nostril than the left. Some patients with normal smell identification test scores had delayed evoked potentials. In the pathological examination of olfactory bulbs from eight brains, changes characteristic of Parkinson's disease (Lewy bodies) were seen in every olfactory bulb, particularly in the anterior olfactory nucleus, and were sufficiently distinct to allow a presumptive diagnosis of Parkinson's disease. CONCLUSIONS: Olfactory damage in Parkinson's disease is consistent and severe and may provide an important clue to the aetiology of the disease. Images PMID:9153598

  7. A Brief Olfactory Test for Alzheimer’s Disease

    PubMed Central

    Stamps, Jennifer J.; Bartoshuk, Linda M.; Heilman, Kenneth M.

    2013-01-01

    Background The early diagnosis of Alzheimer’s disease (AD) may help reduce disability, enhance quality of life, and aid clinical trials. Portions of olfactory cortex are the initial sites of AD pathology and patients with AD often have more degeneration of their left than right hemisphere. Since the olfactory epithelium projects mainly to the ipsilateral olfactory cortex, patients with AD may demonstrate an asymmetrical (left greater than right) decrement of odor detection sensitivity. This retrospective, case-control study assessed a quick olfactory test that may help diagnose AD. Methods Participants with probable AD (N=18), mild cognitive impairment (MCI, N=24), other causes of dementia (OD, N=26) and matched controls (OC, N=26) were tested, with closed eyes, for their ability to detect an odor, one nostril at a time. A container of 14g of peanut butter was opened, held medially at the bottom of a 30 cm ruler, and moved up 1cm at a time during the participants’ exhale. Upon odor detection, the distance between the subject’s nostril and container was measured. Results The mean odor detection distance of AD patients’ left nostril (5.1 cm), and not their right (17.4 cm), was significantly less (F(3,90) = 22.28, p < 0.0001) than the other groups. The mean, standard error, and 95% Confidence Interval of the L R nostril odor detection difference (cm) for AD was −12.4 ±0.5, (−15.0, −9.8); for MCI was −1.9 ±1.2, (−4.2,0.4); for OD was 4.8 ±1.0, (2.6,6.9); and for OC was 0.0 ±1.4 (−2.2,2.1). Conclusion This non-invasive and inexpensive left-right nostril odor detection test appears to be a sensitive and specific test for probable AD. PMID:23927938

  8. Evaluation of the effect of cigarette smoking on the olfactory neuroepithelium of New Zealand white rabbit, using scanning electron microscope.

    PubMed

    Iskander, Nagi M; El-Hennawi, Diaa M; Yousef, Tarek F; El-Tabbakh, Mohammed T; Elnahriry, Tarek A

    2017-03-01

    To detect ultra-structural changes of Rabbit's olfactory neuro-epithelium using scanning electron microscope after exposure to cigarette smoking. Sixty six rabbits (Pathogen free New Zealand white rabbits weighing 1-1.5 kg included in the study were randomly assigned into one of three groups: control group did not expose to cigarette smoking, study group 1 was exposed to cigarette smoking for 3 months and study group 2 was exposed to cigarette smoking 3 months and then stopped for 2 months. Olfactory neuro-epithelium from all rabbits were dissected and examined under Philips XL-30 scanning electron microscope. Changes that were found in the rabbits of study group 1 in comparison to control group were loss of microvilli of sustentacular cells (p = 0.016) and decreases in distribution of specialized cilia of olfactory receptor cells (p = 0.046). Also respiratory metaplasia was detected. These changes were reversible in study group 2. Cigarette smoking causes ultra-structural changes in olfactory neuro-epithelium which may explain why smell was affected in cigarette smokers. Most of these changes were reversible after 45 days of cessation of cigarette smoking to the rabbits.

  9. [Olfactory sensory perception].

    PubMed

    Fuentes, Aler; Fresno, María Javiera; Santander, Hugo; Valenzuela, Saúl; Gutiérrez, Mario Felipe; Miralles, Rodolfo

    2011-03-01

    The five senses have had a fundamental importance for survival and socialization of human beings. From an evolutionary point of view the sense of smell is the oldest. This sense has a strong representation within the genome, allowing the existence of many types of receptors that allow us to capture multiple volatile odor producing molecules, sending electrical signals to higher centers to report the outside world. Several cortical areas are activated in the brain, which are interconnected to form an extensive and complex neural network, linking for example, areas involved with memory and emotions, thus giving this sense of perceptual richness. While the concept of flavor is largely related to the sense of taste, smell provides the necessary integration with the rest of the senses and higher functions. Fully understanding the sense of smell is relevant to health professionals. Knowing the characteristics of the receptors, the transduction processes and convergence of information in the higher centers involved, we can properly detect olfactory disorders in our patients.

  10. Contribution of pheromones processed by the main olfactory system to mate recognition in female mammals.

    PubMed

    Baum, Michael J

    2012-01-01

    Until recently it was widely believed that the ability of female mammals (with the likely exception of women) to identify and seek out a male breeding partner relied on the detection of non-volatile male pheromones by the female's vomeronasal organ (VNO) and their subsequent processing by a neural circuit that includes the accessory olfactory bulb (AOB), vomeronasal amygdala, and hypothalamus. Emperical data are reviewed in this paper that demonstrate the detection of volatile pheromones by the main olfactory epithelium (MOE) of female mice which, in turn, leads to the activation of a population of glomeruli and abutting mitral cells in the main olfactory bulb (MOB). Anatomical results along with functional neuroanatomical data demonstrate that some of these MOB mitral cells project to the vomeronasal amygdala. These particular MOB mitral cells were selectively activated (i.e., expressed Fos protein) by exposure to male as opposed to female urinary volatiles. A similar selectivity to opposite sex urinary volatiles was also seen in mitral cells of the AOB of female mice. Behavioral data from female mouse, ferret, and human are reviewed that implicate the main olfactory system, in some cases interacting with the accessory olfactory system, in mate recognition.

  11. Flash Photolysis of Caged Compounds in the Cilia of Olfactory Sensory Neurons

    PubMed Central

    Boccaccio, Anna; Sagheddu, Claudia; Menini, Anna

    2011-01-01

    Photolysis of caged compounds allows the production of rapid and localized increases in the concentration of various physiologically active compounds1. Caged compounds are molecules made physiologically inactive by a chemical cage that can be broken by a flash of ultraviolet light. Here, we show how to obtain patch-clamp recordings combined with photolysis of caged compounds for the study of olfactory transduction in dissociated mouse olfactory sensory neurons. The process of olfactory transduction (Figure 1) takes place in the cilia of olfactory sensory neurons, where odorant binding to receptors leads to the increase of cAMP that opens cyclic nucleotide-gated (CNG) channels2. Ca entry through CNG channels activates Ca-activated Cl channels. We show how to dissociate neurons from the mouse olfactory epithelium3 and how to activate CNG channels or Ca-activated Cl channels by photolysis of caged cAMP4 or caged Ca5. We use a flash lamp6,7 to apply ultraviolet flashes to the ciliary region to uncage cAMP or Ca while patch-clamp recordings are taken to measure the current in the whole-cell voltage-clamp configuration8-11. PMID:22064384

  12. Flash photolysis of caged compounds in the cilia of olfactory sensory neurons.

    PubMed

    Boccaccio, Anna; Sagheddu, Claudia; Menini, Anna

    2011-10-29

    Photolysis of caged compounds allows the production of rapid and localized increases in the concentration of various physiologically active compounds. Caged compounds are molecules made physiologically inactive by a chemical cage that can be broken by a flash of ultraviolet light. Here, we show how to obtain patch-clamp recordings combined with photolysis of caged compounds for the study of olfactory transduction in dissociated mouse olfactory sensory neurons. The process of olfactory transduction (Figure 1) takes place in the cilia of olfactory sensory neurons, where odorant binding to receptors leads to the increase of cAMP that opens cyclic nucleotide-gated (CNG) channels. Ca entry through CNG channels activates Ca-activated Cl channels. We show how to dissociate neurons from the mouse olfactory epithelium and how to activate CNG channels or Ca-activated Cl channels by photolysis of caged cAMP or caged Ca. We use a flash lamp to apply ultraviolet flashes to the ciliary region to uncage cAMP or Ca while patch-clamp recordings are taken to measure the current in the whole-cell voltage-clamp configuration.

  13. Vasoactive intestinal polypeptide mediates circadian rhythms in mammalian olfactory bulb and olfaction.

    PubMed

    Miller, Jae-Eun Kang; Granados-Fuentes, Daniel; Wang, Thomas; Marpegan, Luciano; Holy, Timothy E; Herzog, Erik D

    2014-04-23

    Accumulating evidence suggests that the olfactory bulbs (OBs) function as an independent circadian system regulating daily rhythms in olfactory performance. However, the cells and signals in the olfactory system that generate and coordinate these circadian rhythms are unknown. Using real-time imaging of gene expression, we found that the isolated olfactory epithelium and OB, but not the piriform cortex, express similar, sustained circadian rhythms in PERIOD2 (PER2). In vivo, PER2 expression in the OB of mice is circadian, approximately doubling with a peak around subjective dusk. Furthermore, mice exhibit circadian rhythms in odor detection performance with a peak at approximately subjective dusk. We also found that circadian rhythms in gene expression and odor detection performance require vasoactive intestinal polypeptide (VIP) or its receptor VPAC2R. VIP is expressed, in a circadian manner, in interneurons in the external plexiform and periglomerular layers, whereas VPAC2R is expressed in mitral and external tufted cells in the OB. Together, these results indicate that VIP signaling modulates the output from the OB to maintain circadian rhythms in the mammalian olfactory system.

  14. Evidence for distinct signaling mechanisms in two mammalian olfactory sense organs.

    PubMed

    Berghard, A; Buck, L B; Liman, E R

    1996-03-19

    In mammals, olfactory stimuli are detected by sensory neurons at two distinct sites: the olfactory epithelium (OE) of the nasal cavity and the neuroepithelium of the vomeronasal organ (VNO). While the OE can detect volatile chemicals released from numerous sources, the VNO appears to be specialized to detect pheromones that are emitted by other animals and that convey information of behavioral or physiological importance. The mechanisms underlying sensory transduction in the OE have been well studied and a number of components of the transduction cascade have been cloned. Here, we investigated sensory transduction in the VNO by asking whether VNO neurons express molecules that have been implicated in sensory transduction in the OE. Using in situ hybridization and Northern blot analyses, we found that most of the olfactory transduction components examined, including the guanine nucleotide binding protein alpha subunit (G-alpha-olf), adenylyl cyclase type III, and an olfactory cyclic nucleotide-gated (CNG) channel subunit (oCNC1), are not expressed by VNO sensory neurons. In contrast, VNO neurons do express a second olfactory CNG channel subunit (oCNC2). These results indicate that VNO sensory transduction is distinct from that in the OE but raise the possibility that, like OE sensory transduction, sensory transduction in the VNO might involve cyclic nucleotide-gated ion channels.

  15. Channel properties of the splicing isoforms of the olfactory calcium-activated chloride channel Anoctamin 2.

    PubMed

    Ponissery Saidu, Samsudeen; Stephan, Aaron B; Talaga, Anna K; Zhao, Haiqing; Reisert, Johannes

    2013-06-01

    Anoctamin (ANO)2 (or TMEM16B) forms a cell membrane Ca(2+)-activated Cl(-) channel that is present in cilia of olfactory receptor neurons, vomeronasal microvilli, and photoreceptor synaptic terminals. Alternative splicing of Ano2 transcripts generates multiple variants with the olfactory variants skipping exon 14 and having alternative splicing of exon 4. In the present study, 5' rapid amplification of cDNA ends analysis was conducted to characterize the 5' end of olfactory Ano2 transcripts, which showed that the most abundant Ano2 transcripts in the olfactory epithelium contain a novel starting exon that encodes a translation initiation site, whereas transcripts of the publically available sequence variant, which has an alternative and longer 5' end, were present in lower abundance. With two alternative starting exons and alternative splicing of exon 4, four olfactory ANO2 isoforms are thus possible. Patch-clamp experiments in transfected HEK293T cells expressing these isoforms showed that N-terminal sequences affect Ca(2+) sensitivity and that the exon 4-encoded sequence is required to form functional channels. Coexpression of the two predominant isoforms, one with and one without the exon 4 sequence, as well as coexpression of the two rarer isoforms showed alterations in channel properties, indicating that different isoforms interact with each other. Furthermore, channel properties observed from the coexpression of the predominant isoforms better recapitulated the native channel properties, suggesting that the native channel may be composed of two or more splicing isoforms acting as subunits that together shape the channel properties.

  16. Olfactory Neuroblastoma with Divergent Differentiation: An Unusual Histologic Finding in a Rare Tumor.

    PubMed

    Meyer, Charles; Hamersley, Erin R S; Manosalva, Rodolfo E; Torske, Kevin; McIntyre, Nicole; Mitchell, Allen

    2017-02-06

    Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of the sinonasal tract that arises from olfactory epithelium. There have been reports, mainly in tumors treated with chemoradiation or with distant metastases, describing focal histologic changes of divergent cell populations within archetypal ONB. Only three cases have been reported of ONB coexisting with non-neuroendocrine tumors. We describe our experience with a 35-year-old male with a nasal cavity mass extending into the anterior cranial fossa. Pathology revealed this to be a high grade malignant neoplasm with features of olfactory neuroblastoma and a significant divergent population of pancytokeratin and epithelial membrane antigen-reactive cells. The patient underwent combined endoscopic and open craniofacial resection followed by adjuvant chemoradiation. We describe the clinical presentation, treatment, and outcome followed by a review of the literature. Surgical pathology clearly demonstrated two cell populations evenly distributed and displaying classic histologic and immunohistochemical markers of ONB, as well as poorly differentiated cells with an epithelial immunophenotype. The patient is now 16 months status post completion of treatment with no evidence of recurrence. Our patient's presentation is unique and unusual in that the tumor demonstrated a high grade olfactory neuroblastoma and a divergent, epithelial-marker reactive cell population in the same tumor. This combined appearance is unusual and may represent an "olfactory carcinoma". Only one previous case has reported carcinomatous involvement of an ONB. There is insufficient information in the literature to draw conclusions on the impact these divergent cell populations have on prognosis or treatment.

  17. Evolution of insect olfactory receptors

    PubMed Central

    Missbach, Christine; Dweck, Hany KM; Vogel, Heiko; Vilcinskas, Andreas; Stensmyr, Marcus C; Hansson, Bill S; Grosse-Wilde, Ewald

    2014-01-01

    The olfactory sense detects a plethora of behaviorally relevant odor molecules; gene families involved in olfaction exhibit high diversity in different animal phyla. Insects detect volatile molecules using olfactory (OR) or ionotropic receptors (IR) and in some cases gustatory receptors (GRs). While IRs are expressed in olfactory organs across Protostomia, ORs have been hypothesized to be an adaptation to a terrestrial insect lifestyle. We investigated the olfactory system of the primary wingless bristletail Lepismachilis y-signata (Archaeognatha), the firebrat Thermobia domestica (Zygentoma) and the neopteran leaf insect Phyllium siccifolium (Phasmatodea). ORs and the olfactory coreceptor (Orco) are with very high probability lacking in Lepismachilis; in Thermobia we have identified three Orco candidates, and in Phyllium a fully developed OR/Orco-based system. We suggest that ORs did not arise as an adaptation to a terrestrial lifestyle, but evolved later in insect evolution, with Orco being present before the appearance of ORs. DOI: http://dx.doi.org/10.7554/eLife.02115.001 PMID:24670956

  18. Olfactory and gustatory functions and its relation to body weight.

    PubMed

    Skrandies, Wolfgang; Zschieschang, Romy

    2015-04-01

    In the present study we investigated the influence of body weight as defined by BMI on gustatory and olfactory perception. A total of 66 healthy adults (41 females; 25 males) participated in psychophysical measurements using the "Sniffin' Sticks" test and "Taste Strips" test. Odor thresholds as well as discrimination and identification performance were determined. Tests of gustatory function involved the identification and thresholds of sweet, sour, salty, or bitter taste. In this study, all subjects were healthy participants in a middle age range (between 20 and 56 years of age). Persons with an extreme BMI value were excluded. Subjects were classified according to their BMI in four groups: (1) 15-19.9 kg/m, (2) 20-24.9 kg/m, (3) 25-29.9 kg/m, and (4) >30 kg/m. We did not observe an overall effect of BMI on general sensory sensitivity. There was a significant influence of BMI on olfactory thresholds (F(3,62)=2.79; p<0.047) which increased with increasing BMI. In a similar line, the gustatory thresholds for "salty" were significantly higher with higher BMI (F(3,62)=3.06; p<0.035). Olfactory discrimination and identification was not affected by BMI. Thresholds for odor and sweet or salty taste were also correlated. Our data show that body weight influences gustatory and olfactory perception in healthy adults. Increasing BMI is associated with a decrease in olfactory and taste sensitivity. These findings may have implications for the understanding of pathophysiological mechanisms in patients.

  19. In vivo visualization of olfactory pathophysiology induced by intranasal cadmium instillation in mice

    PubMed Central

    Czarnecki, Lindsey A.; Moberly, Andrew H.; Rubinstein, Tom; Turkel, Daniel J.; Pottackal, Joseph; McGann, John P.

    2013-01-01

    Intranasal exposure to cadmium has been related to olfactory dysfunction in humans and to nasal epithelial damage and altered odorant-guided behavior in rodent models. The pathophysiology underlying these deficits has not been fully elucidated. Here we use optical imaging techniques to visualize odorant-evoked neurotransmitter release from the olfactory nerve into the brain’s olfactory bulbs in vivo in mice. Intranasal cadmium chloride instillations reduced this sensory activity by up to 91% in a dose-dependent manner. In the olfactory bulbs, afferents from the olfactory epithelium could be quantified by their expression of a genetically-encoded fluorescent marker for olfactory marker protein. At the highest dose tested, cadmium exposure reduced the density of these projections by 20%. In a behavioral psychophysical task, mice were trained to sample from an odor port and make a response when they detected an odorant against a background of room air. After intranasal cadmium exposure, mice were unable to detect the target odor. These experiments serve as proof of concept for a new approach to the study of the neural effects of inhaled toxicants. The use of in vivo functional imaging of the neuronal populations exposed to the toxicant permits the direct observation of primary pathophysiology. In this study optical imaging revealed significant reductions in odorant-evoked release from the olfactory nerve at a cadmium chloride dose two orders of magnitude less than that required to induce morphological changes in the nerve in the same animals, demonstrating that it is a more sensitive technique for assessing the consequences of intranasal neurotoxicant exposure. This approach is potentially useful in exploring the effects of any putative neurotoxicant that can be delivered intranasally. PMID:21443902

  20. Brain fingerprints of olfaction: a novel structural method for assessing olfactory cortical networks in health and disease

    PubMed Central

    Fjaeldstad, A.; Fernandes, H. M.; Van Hartevelt, T. J.; Gleesborg, C.; Møller, A.; Ovesen, T.; Kringelbach, M. L.

    2017-01-01

    Olfactory deficits are a common (often prodromal) symptom of neurodegenerative or psychiatric disorders. As such, olfaction could have great potential as an early biomarker of disease, for example using neuroimaging to investigate the breakdown of structural connectivity profile of the primary olfactory networks. We investigated the suitability for this purpose in two existing neuroimaging maps of olfactory networks. We found problems with both existing neuroimaging maps in terms of their structural connectivity to known secondary olfactory networks. Based on these findings, we were able to merge the existing maps to a new template map of olfactory networks with connections to all key secondary olfactory networks. We introduce a new method that combines diffusion tensor imaging with probabilistic tractography and pattern recognition techniques. This method can obtain comprehensive and reliable fingerprints of the structural connectivity underlying the neural processing of olfactory stimuli in normosmic adults. Combining the novel proposed method for structural fingerprinting with the template map of olfactory networks has great potential to be used for future neuroimaging investigations of olfactory function in disease. With time, the proposed method may even come to serve as structural biomarker for early detection of disease. PMID:28195241

  1. Fragile X mental retardation protein regulates olfactory sensitivity but not odorant discrimination.

    PubMed

    Schilit Nitenson, Arielle; Stackpole, Emily E; Truszkowski, Torrey L S; Midroit, Maellie; Fallon, Justin R; Bath, Kevin G

    2015-06-01

    Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and is characterized by cognitive impairments and altered sensory function. It is caused by absence of fragile X mental retardation protein (FMRP), an RNA-binding protein essential for normal synaptic plasticity and function. Animal models have provided important insights into mechanisms through which loss of FMRP impacts cognitive and sensory development and function. While FMRP is highly enriched in the developing and adult olfactory bulb (OB), its role in olfactory sensory function remains poorly understood. Here, we used a mouse model of FXS, the fmr1 (-/y) mouse, to test whether loss of FMRP impacts olfactory discrimination, habituation, or sensitivity using a spontaneous olfactory cross-habituation task at a range of odorant concentrations. We demonstrated that fmr1 (-/y) mice have a significant decrease in olfactory sensitivity compared with wild type controls. When we controlled for differences in sensitivity, we found no effect of loss of FMRP on the ability to habituate to or spontaneously discriminate between odorants. These data indicate that loss of FMRP significantly alters olfactory sensitivity, but not other facets of basal olfactory function. These findings have important implications for future studies aimed at understanding the role of FMRP on sensory functioning.

  2. Integration of Visual and Olfactory Cues in Host Plant Identification by the Asian Longhorned Beetle, Anoplophora glabripennis (Motschulsky) (Coleoptera: Cerambycidae)

    PubMed Central

    L.Yv, Fei; Hai, Xiaoxia; Wang, Zhigang; Yan, Aihua; Liu, Bingxiang; Bi, Yongguo

    2015-01-01

    Some insects use host and mate cues, including odor, color, and shape, to locate and recognize their preferred hosts and mates. Previous research has shown that the Asian longicorn beetle, Anoplophora glabripennis (Motschulsky), uses olfactory cues to locate host plants and differentiate them from non-host plants. However, whether A. glabripennis adults use visual cues or a combination of visual and olfactory cues remains unclear. In this study, we tested the host location and recognition behavior in A. glabripennis, which infests a number of hardwood species and causes considerable economic losses in North America, Europe and Asia. We determined the relative importance of visual and olfactory cues from Acer negundo in host plant location and recognition, as well as in the discrimination of non-host plants (Sabina chinensis and Pinus bungeana), by female and male A. glabripennis. Visual and olfactory cues from the host plants (A. negundo), alone and combined, attracted significantly more females and males than equivalent cues from non-host plants (S. chinensis and P. bungeana). Furthermore, the combination of visual and olfactory cues of host plants attracted more adults than either cue alone, and visual cues alone attracted significantly more adults than olfactory cues alone. This finding suggests that adult A. glabripennis has an innate preference for the visual and/or olfactory cues of its host plants (A. negundo) over those of the non-host plant and visual cues are initially more important than olfactory cues for orientation; furthermore, this finding also suggests that adults integrate visual and olfactory cues to find their host plants. Our results indicate that different modalities of host plant cues should be considered together to understand fully the communication between host plants and Asian longhorned beetles. PMID:26556100

  3. Windscapes and olfactory foraging in a large carnivore.

    PubMed

    Togunov, Ron R; Derocher, Andrew E; Lunn, Nicholas J

    2017-04-12

    The theoretical optimal olfactory search strategy is to move cross-wind. Empirical evidence supporting wind-associated directionality among carnivores, however, is sparse. We examined satellite-linked telemetry movement data of adult female polar bears (Ursus maritimus) from Hudson Bay, Canada, in relation to modelled winds, in an effort to understand olfactory search for prey. In our results, the predicted cross-wind movement occurred most frequently at night during winter, the time when most hunting occurs, while downwind movement dominated during fast winds, which impede olfaction. Migration during sea ice freeze-up and break-up was also correlated with wind. A lack of orientation during summer, a period with few food resources, likely reflected reduced cross-wind search. Our findings represent the first quantitative description of anemotaxis, orientation to wind, for cross-wind search in a large carnivore. The methods are widely applicable to olfactory predators and their prey. We suggest windscapes be included as a habitat feature in habitat selection models for olfactory animals when evaluating what is considered available habitat.

  4. A further analysis of olfactory cortex development

    PubMed Central

    Pedraza, María; De Carlos, Juan A.

    2012-01-01

    The olfactory cortex (OC) is a complex yet evolutionarily well-conserved brain region, made up of heterogeneous cell populations that originate in different areas of the developing telencephalon. Indeed, these cells are among the first cortical neurons to differentiate. To date, the development of the OC has been analyzed using birthdating techniques along with molecular markers and in vivo or in vitro tracking methods. In the present study, we sought to determine the origin and adult fate of these cell populations using ultrasound-guided in utero injections and electroporation of different genomic plasmids into the lateral walls of the ventricles. Our results provide direct evidence that in the mouse OC, cell fate is determined by the moment and place of origin of each specific cell populations. Moreover, by combining these approaches with the analysis of specific cell markers, we show that the presence of pallial and subpallial markers in these areas is independent of cell origin. PMID:22969708

  5. Pericentrin, a centrosomal protein related to microcephalic primordial dwarfism, is required for olfactory cilia assembly in mice.

    PubMed

    Miyoshi, Ko; Kasahara, Kyosuke; Miyazaki, Ikuko; Shimizu, Shoko; Taniguchi, Manabu; Matsuzaki, Shinsuke; Tohyama, Masaya; Asanuma, Masato

    2009-10-01

    The Drosophila pericentrin-like protein has been shown to be essential for the formation of the sensory cilia of chemosensory and mechanosensory neurons by mutant analysis in flies, while the in vivo function of pericentrin, a well-studied mammalian centrosomal protein related to microcephalic primordial dwarfism, has been unclear. To determine whether pericentrin is required for ciliogenesis in mammals, we generated and analyzed mice with a hypomorphic mutation of Pcnt encoding the mouse pericentrin. Immunofluorescence analysis demonstrated that olfactory cilia of chemosensory neurons in the nasal olfactory epithelium were malformed in the homozygous mutant mice. On the other hand, the assembly of motile and primary cilia of non-neuronal epithelial cells and the formation of sperm flagella were not affected in the Pcnt-mutant mice. The defective assembly of olfactory cilia in the mutant was apparent from birth. The mutant animals displayed reduced olfactory performance in agreement with the compromised assembly of olfactory cilia. Our findings suggest that pericentrin is essential for the assembly of chemosensory cilia of olfactory receptor neurons, but it is not globally required for cilia formation in mammals.

  6. Heightened Olfactory Sensitivity in Young Females with Recent-Onset Anorexia Nervosa and Recovered Individuals

    PubMed Central

    Bentz, Mette; Guldberg, Johanne; Vangkilde, Signe; Pedersen, Tine; Plessen, Kerstin Jessica; Jepsen, Jens Richardt Moellegaard

    2017-01-01

    Introduction Olfaction may be related to food restriction and weight loss. However, reports regarding olfactory function in individuals with anorexia nervosa (AN) have been inconclusive. Objective Characterize olfactory sensitivity and identification in female adolescents and young adults with first-episode AN and young females recovered from AN. Methods We used the Sniffin’ Sticks Odor Threshold Test and Odor Identification Test to assess 43 participants with first-episode AN, 27 recovered participants, and 39 control participants. Participants completed the Importance of Olfaction questionnaire, the Beck Youth Inventory and the Eating Disorder Inventory. We also conducted a psychiatric diagnostic interview and the Autism Diagnostic Observation Schedule with participants. Results Both clinical groups showed heightened olfactory sensitivity. After excluding participants with depression, participants with first-episode AN identified more odors than recovered participants. Conclusion Heightened olfactory sensitivity in AN may be independent of clinical status, whereas only individuals with current AN and without depression show more accurate odor identification. PMID:28060877

  7. Signature microRNAs in human cornea limbal epithelium.

    PubMed

    Teng, Yufei; Wong, Hoi Kin; Jhanji, Vishal; Chen, Jian Huan; Young, Alvin Lerrmann; Zhang, Mingzhi; Choy, Kwong Wai; Mehta, Jodhbir Singh; Pang, Chi Pui; Yam, Gary Hin-Fai

    2015-05-01

    This study was aimed to identify the signature microRNAs, which regulate the biological processes of corneal epithelial progenitor cell (CEPC) homeostasis and regulation through characterizing the differential expression profile of microRNAs in human limbal epithelium containing adult CEPC versus central corneal epithelium without CEPC. MicroRNA microarray had identified 37 microRNAs enriched in human corneal epithelium. Among them, nine were significantly upregulated in limbal epithelium and one in central corneal epithelium after validation by TaqMan® real-time polymerase chain reaction. In addition to our previous finding of miR-143 and 145, the expression of miR-10b, 126, and 155 was localized in limbal epithelium (LE) (predominantly basal layers) by using locked nucleic acid-based in situ hybridization. Potential target genes were predicted by TargetScan Human v6.0 and compared to the reported human cornea epithelial gene profile GSE5543. Analyzed by web-based Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and DAVID Functional Annotation Bioinformatics Resources v6.7, the downregulated genes were involved in pathways of immune response and cellular protection, apoptosis, and cell movement whereas upregulated genes with cell survival, cell-matrix interaction, and cell-cell adhesion. We found a constant occurrence of miR-143, 145, and 155 in all KEGG pathways regulating limbal epithelial events. By Ingenuity Systems (IPA®) analysis, these microRNAs could cooperatively regulate cell growth and apoptosis via tumor necrosis factor activation and MYC repression. Our findings thus suggest a unique microRNA signature existing in human limbal epithelium and participating in CEPC homeostasis.

  8. Rapid and continuous activity-dependent plasticity of olfactory sensory input

    PubMed Central

    Cheetham, Claire E. J.; Park, Una; Belluscio, Leonardo

    2016-01-01

    Incorporation of new neurons enables plasticity and repair of circuits in the adult brain. Adult neurogenesis is a key feature of the mammalian olfactory system, with new olfactory sensory neurons (OSNs) wiring into highly organized olfactory bulb (OB) circuits throughout life. However, neither when new postnatally generated OSNs first form synapses nor whether OSNs retain the capacity for synaptogenesis once mature, is known. Therefore, how integration of adult-born OSNs may contribute to lifelong OB plasticity is unclear. Here, we use a combination of electron microscopy, optogenetic activation and in vivo time-lapse imaging to show that newly generated OSNs form highly dynamic synapses and are capable of eliciting robust stimulus-locked firing of neurons in the mouse OB. Furthermore, we demonstrate that mature OSN axons undergo continuous activity-dependent synaptic remodelling that persists into adulthood. OSN synaptogenesis, therefore, provides a sustained potential for OB plasticity and repair that is much faster than OSN replacement alone. PMID:26898529

  9. Apoptosis and the Airway Epithelium

    PubMed Central

    White, Steven R.

    2011-01-01

    The airway epithelium functions as a barrier and front line of host defense in the lung. Apoptosis or programmed cell death can be elicited in the epithelium as a response to viral infection, exposure to allergen or to environmental toxins, or to drugs. While apoptosis can be induced via activation of death receptors on the cell surface or by disruption of mitochondrial polarity, epithelial cells compared to inflammatory cells are more resistant to apoptotic stimuli. This paper focuses on the response of airway epithelium to apoptosis in the normal state, apoptosis as a potential regulator of the number and types of epithelial cells in the airway, and the contribution of epithelial cell apoptosis in important airways diseases. PMID:22203854

  10. Hypothyroidism Affects Olfactory Evoked Potentials.

    PubMed

    Świdziński, Teodor; Linkowska-Świdzińska, Kamila; Czerniejewska-Wolska, Hanna; Wiskirska-Woźnica, Bożena; Owecki, Maciej; Głowacka, Maria Danuta; Frankowska, Anna; Łącka, Katarzyna; Glapiński, Mariusz; Maciejewska-Szaniec, Zofia; Świdziński, Piotr

    Background. Objective electrophysiological methods for investigations of the organ of smell consist in recordings of olfactory cortex responses to specific, time restricted odor stimuli. In hypothyroidism have impaired sense of smell. Material and Methods. Two groups: control of 31 healthy subjects and study group of 21 with hypothyroidism. The inclusion criterion for the study group was the TSH range from 3.54 to 110 μIU/mL. Aim. Assessment of the latency time of evoked responses from the olfactory nerve N1 and the trigeminal nerve N5 using two smells of mint and anise in hypothyroidism. Results. The smell perception in subjective olfactory tests was normal in 85% of the hypothyroid group. Differences were noticed in the objective tests. The detailed intergroup analysis of latency times of recorded cortical responses PN5 and PN1 performed by means between the groups of patients with overt clinical hypothyroidism versus subclinical hypothyroidism demonstrated a significant difference (p < 0.05) whereas no such differences were found between the control group versus subclinical hypothyroidism group (p > 0.05). Conclusion. We can conclude that registration of cortex potentials at irritation of olfactory and trigeminal nerves offers possibilities for using this method as an objective indicator of hypothyroidism severity and prognostic process factor.

  11. Hypothyroidism Affects Olfactory Evoked Potentials

    PubMed Central

    Świdziński, Teodor; Czerniejewska-Wolska, Hanna; Wiskirska-Woźnica, Bożena; Owecki, Maciej; Głowacka, Maria Danuta; Frankowska, Anna; Łącka, Katarzyna; Glapiński, Mariusz; Maciejewska-Szaniec, Zofia; Świdziński, Piotr

    2016-01-01

    Background. Objective electrophysiological methods for investigations of the organ of smell consist in recordings of olfactory cortex responses to specific, time restricted odor stimuli. In hypothyroidism have impaired sense of smell. Material and Methods. Two groups: control of 31 healthy subjects and study group of 21 with hypothyroidism. The inclusion criterion for the study group was the TSH range from 3.54 to 110 μIU/mL. Aim. Assessment of the latency time of evoked responses from the olfactory nerve N1 and the trigeminal nerve N5 using two smells of mint and anise in hypothyroidism. Results. The smell perception in subjective olfactory tests was normal in 85% of the hypothyroid group. Differences were noticed in the objective tests. The detailed intergroup analysis of latency times of recorded cortical responses PN5 and PN1 performed by means between the groups of patients with overt clinical hypothyroidism versus subclinical hypothyroidism demonstrated a significant difference (p < 0.05) whereas no such differences were found between the control group versus subclinical hypothyroidism group (p > 0.05). Conclusion. We can conclude that registration of cortex potentials at irritation of olfactory and trigeminal nerves offers possibilities for using this method as an objective indicator of hypothyroidism severity and prognostic process factor. PMID:27656655

  12. Assessment of olfactory function and androstenone odor thresholds in humans with or without functional occlusion of the vomeronasal duct.

    PubMed

    Knecht, Michael; Lundström, Johan N; Witt, Martin; Hüttenbrink, Karl-Bernd; Heilmann, Stefan; Hummel, Thomas

    2003-12-01

    To obtain information on the possible role of the vomeronasal duct (VND) in odor perception and human pheromone detection, the present study investigated different aspects of olfactory function, including thresholds for androstenone in adults with or without detectable VNDs. The study also examined correlations between detection thresholds of androstenone odor and general olfactory function. Subjects' olfaction was assessed with tests for odor identification, odor discrimination, and phenyl ethyl alcohol odor threshold. Measurements were performed on 1 side only, with and without covering the VND. Subjects with or without detectable VNDs did not differ in olfactory sensitivity or androstenone odor thresholds. A small but significant correlation was found between detection thresholds of androstenone and general olfactory function. Finally, covering of the VND did not affect olfactory function or androstenone sensitivity. Results suggest that the human VND does not play a major role in sensitivity toward odorants or the perception of androstenone.

  13. Ion Transporter NKCC1, Modulator of Neurogenesis in Murine Olfactory Neurons*

    PubMed Central

    Haering, Claudia; Kanageswaran, Ninthujah; Bouvain, Pascal; Scholz, Paul; Altmüller, Janine; Becker, Christian; Gisselmann, Günter; Wäring-Bischof, Janine; Hatt, Hanns

    2015-01-01

    Olfaction is one of the most crucial senses for vertebrates regarding foraging and social behavior. Therefore, it is of particular interest to investigate the sense of smell, its function on a molecular level, the signaling proteins involved in the process and the mechanism of required ion transport. In recent years, the precise role of the ion transporter NKCC1 in olfactory sensory neuron (OSN) chloride accumulation has been a controversial subject. NKCC1 is expressed in OSNs and is involved in chloride accumulation of dissociated neurons, but it had not been shown to play a role in mouse odorant sensation. Here, we present electro-olfactogram recordings (EOG) demonstrating that NKCC1-deficient mice exhibit significant defects in perception of a complex odorant mixture (Henkel100) in both air-phase and submerged approaches. Using next generation sequencing (NGS) and RT-PCR experiments of NKCC1-deficient and wild type mouse transcriptomes, we confirmed the absence of a highly expressed ion transporter that could compensate for NKCC1. Additional histological investigations demonstrated a reduced number of cells in the olfactory epithelium (OE), resulting in a thinner neuronal layer. Therefore, we conclude that NKCC1 is an important transporter involved in chloride ion accumulation in the olfactory epithelium, but it is also involved in OSN neurogenesis. PMID:25713142

  14. Olfactory assessment using the NIH Toolbox

    PubMed Central

    Doty, Richard L.; Murphy, Claire; Frank, Robert; Hoffman, Howard J.; Maute, Christopher; Kallen, Michael A.; Slotkin, Jerry

    2013-01-01

    The human olfactory system provides us with information about our environment that is critical to our physical and psychological well-being. Individuals can vary widely in their ability to detect, recognize, and identify odors, but still be within the range of normal function. Although several standardized tests of odor identification are available, few specifically address the issues in testing very young children, most of whom are likely to be unfamiliar with many of the odor stimuli used in adult tests and have limited ability to read and identify labels to select among choices. Based on the format of the San Diego Odor Identification Test and the delivery system of the University of Pennsylvania Smell Identification Test, we developed 2 versions of an odor identification test using standardized odor stimuli in a scratch-and-sniff format in which participants match 5 (children) or 9 (adults) odors to pictures representing the odor source. Results from normative testing and validation showed that for most participants, the test could be completed in 5 minutes or less and that the poorer performance among the youngest children and the elderly was consistent with data from tests with larger numbers of items. Expanding on the pediatric version of the test with adult-specific and public health–relevant odors increased the ecological validity of the test and facilitated comparisons of intraindividual performance across developmental stages. PMID:23479541

  15. Functional transformations of odor inputs in the mouse olfactory bulb

    PubMed Central

    Adam, Yoav; Livneh, Yoav; Miyamichi, Kazunari; Groysman, Maya; Luo, Liqun; Mizrahi, Adi

    2014-01-01

    Sensory inputs from the nasal epithelium to the olfactory bulb (OB) are organized as a discrete map in the glomerular layer (GL). This map is then modulated by distinct types of local neurons and transmitted to higher brain areas via mitral and tufted cells. Little is known about the functional organization of the circuits downstream of glomeruli. We used in vivo two-photon calcium imaging for large scale functional mapping of distinct neuronal populations in the mouse OB, at single cell resolution. Specifically, we imaged odor responses of mitral cells (MCs), tufted cells (TCs) and glomerular interneurons (GL-INs). Mitral cells population activity was heterogeneous and only mildly correlated with the olfactory receptor neuron (ORN) inputs, supporting the view that discrete input maps undergo significant transformations at the output level of the OB. In contrast, population activity profiles of TCs were dense, and highly correlated with the odor inputs in both space and time. Glomerular interneurons were also highly correlated with the ORN inputs, but showed higher activation thresholds suggesting that these neurons are driven by strongly activated glomeruli. Temporally, upon persistent odor exposure, TCs quickly adapted. In contrast, both MCs and GL-INs showed diverse temporal response patterns, suggesting that GL-INs could contribute to the transformations MCs undergo at slow time scales. Our data suggest that sensory odor maps are transformed by TCs and MCs in different ways forming two distinct and parallel information streams. PMID:25408637

  16. Recurrent Olfactory Neuroblastoma Treated With Cetuximab and Sunitinib

    PubMed Central

    Wang, Lizhi; Ding, Yan; Wei, Lai; Zhao, Dewei; Wang, Ruoyu; Zhang, Yuewei; Gu, Xuesong; Wang, Zhiqiang

    2016-01-01

    Abstract Olfactory neuroblastoma (ONB) is a rare cancer originating in the olfactory epithelium of the nasal vault. The recurrence rate of ONB is high, as the standard treatment of surgery followed by radiotherapy and/or chemotherapy is usually unsuccessful. The use of targeted therapy based on individual genomic variations after cancer relapse has not been reported. Here, we present the case of a 44-year-old man who was diagnosed with recurrent ONB and treated with a regimen developed using whole exome sequencing. Potential targets were first identified and then matched to appropriate drugs. Gene mutations in the genes encoding EGFR, FGFR2, KDR, and RET were discovered in the patient's tumor tissue by whole exome sequencing and the patient was treated with a combination of the targeted drugs cetuximab and sunitinib. Five days after treatment, enhancement magnetic resonance imaging showed a 65% reduction in tumor size, and the Visual analog scale headache scores went down to 2/10 from 10/10. Repeat imaging at 1 month showed a complete response. This study represents the first demonstration of an effective personalized treatment of ONB by targeted drugs, and sheds light on how precision medicine can be used to treat recurrent ONB that fails to respond to routine tumor resection, radiotherapy, and/or chemotherapy. PMID:27149458

  17. Olfactory transduction pathways in the Senegalese sole Solea senegalensis.

    PubMed

    Velez, Z; Hubbard, P C; Barata, E N; Canário, A V M

    2013-09-01

    This study tested whether differences in sensitivity between the upper and lower olfactory epithelia of Solea senegalensis are associated with different odorant receptors and transduction pathways, using the electro-olfactogram. Receptor mechanisms were assessed by cross-adaptation with amino acids (L-cysteine, L-phenylalanine and 1-methyl-L-tryptophan) and bile acids (taurocholic acid and cholic acid). This suggested that relatively specific receptors exist for 1-methyl-L-tryptophan and L-phenylalanine (food-related odorants) in the lower epithelium, and for taurocholic acid (conspecific-derived odorant) in the upper. Inhibition by U73122 [a phospholipase C (PLC) inhibitor] suggested that olfactory responses to amino acids were mediated mostly, but not entirely, by PLC-mediated transduction (IC50 ; 15-55 nM), whereas bile acid responses were mediated by both PLC and adenylate cyclase-cyclic adenosine monophosphate (AC-cAMP) (using SQ-22536; an AC inhibitor). Simultaneous application of both drugs rarely inhibited responses completely, suggesting possible involvement of non-PLC and non-AC mediated mechanisms. For aromatic amino acids and bile acids, there were differences in the contribution of each transduction pathway (PLC, AC and non-PLC and non-AC) between the two epithelia. These results suggest that differences in sensitivity of the two epithelia are associated with differences in odorant receptors and transduction mechanisms.

  18. Expression Profile of Ectopic Olfactory Receptors Determined by Deep Sequencing

    PubMed Central

    Flegel, Caroline; Manteniotis, Stavros; Osthold, Sandra; Hatt, Hanns; Gisselmann, Günter

    2013-01-01

    Olfactory receptors (ORs) provide the molecular basis for the detection of volatile odorant molecules by olfactory sensory neurons. The OR supergene family encodes G-protein coupled proteins that belong to the seven-transmembrane-domain receptor family. It was initially postulated that ORs are exclusively expressed in the olfactory epithelium. However, recent studies have demonstrated ectopic expression of some ORs in a variety of other tissues. In the present study, we conducted a comprehensive expression analysis of ORs using an extended panel of human tissues. This analysis made use of recent dramatic technical developments of the so-called Next Generation Sequencing (NGS) technique, which encouraged us to use open access data for the first comprehensive RNA-Seq expression analysis of ectopically expressed ORs in multiple human tissues. We analyzed mRNA-Seq data obtained by Illumina sequencing of 16 human tissues available from Illumina Body Map project 2.0 and from an additional study of OR expression in testis. At least some ORs were expressed in all the tissues analyzed. In several tissues, we could detect broadly expressed ORs such as OR2W3 and OR51E1. We also identified ORs that showed exclusive expression in one investigated tissue, such as OR4N4 in testis. For some ORs, the coding exon was found to be part of a transcript of upstream genes. In total, 111 of 400 OR genes were expressed with an FPKM (fragments per kilobase of exon per million fragments mapped) higher than 0.1 in at least one tissue. For several ORs, mRNA expression was verified by RT-PCR. Our results support the idea that ORs are broadly expressed in a variety of tissues and provide the basis for further functional studies. PMID:23405139

  19. Functional morphology of the olfactory organ of the tongue sole, Cynoglossus semilaevis

    NASA Astrophysics Data System (ADS)

    Ma, Aijun; Wang, Xin'an

    2010-03-01

    The morphology and structure of the olfactory organ of Cynoglossus semilaevis Günther are described. The oval olfactory sacs on both sides differ in size and in the number of lamellae, with those on the abocular side having smaller sacs and fewer lamellae than those on the ocular side. On the ocular side, the average ratio of sac length to eye diameter is 2.1 (i.e.>1) with an average of 91 lamellae, while on the abocular side, the values were 1.7 (i.e.>1) and 69, respectively. In addition, the surface morphology varies in different parts of the lamella. The frontal part, near the anterior nostril, is a non-sensory margin with cilia-free epidermal cells. Within this is an internal ciliated sensory area, which is intercalated with ciliated receptor cells and a few ciliated non-sensory cells. Additionally, some dense ciliated non-sensory cells make up a non-sensory area, which also contains cilia-free epidermal cells distributed in patches. In the rear of the olfactory sac near the posterior nostril, the lamellae differ in morphology from those of the frontal olfactory sac but are similar in having few ciliated receptor cells. In other words, the surface of the lamellae in the rear part of the olfactory sac is mainly non-sensory. At present, four types of lamellae (I, II, III and IV) have been recognized in relation to the pattern of the sensory epithelium. In this study, the frontal and rear lamellae resembled types I and IV, respectively, but are referred to as types I' and IV' because they are slightly less developed. Data on the ratio of length of lamellae to eye diameter, number of lamellae and the type of surface pattern of the lamellae show that the development of the olfactory system of C. semilaevis facilitates prey capture.

  20. Studies on the correlation with olfactory dysfunction in a transgenic mice model of Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Rasheed, Ameer; Lee, Ji Hye; Suh, Yoo-Hun; Moon, Cheil

    2013-05-01

    Alzheimer's disease (AD) is a progressively debilitating neurodegenerative disorder characterized by the presence of proteinaceous deposits in the brain. AD often results in olfactory dysfunction and impaired olfactory perceptual acuity may be a potential biomarker for early diagnosis of AD. Until recently, there is no Alzheimer's nanoscope or any other high-end microscope developed to be capable of seeing buried feature of AD clearly. Modern neuroimaging techniques are more effective only after the occurrence of cognitive impairment. Therefore, early detection of Alzheimer's disease is critical in developing effective treatment of AD. H and E (Haematoxyline and Eosin) staining is performed for examining gross morphological changes, while TUNEL (transferase (TdT)-mediated dUTP nick end labeling) staining for monitoring neuronal death in the olfactory epithelium (OE). Furthermore, immunohistochemistry and western blot are performed to examine β-amyloid protein expression. AD model animals were Tg2576 (transgenic mice that overexpress a mutated form of the Aβ precursor protein), and 6 month (before onset of AD symptoms) and 14 month (after onset of AD symptoms) old WT (wild type) and transgenic mice were compared in their olfactory system. We found that in OE of Tg2576 mice, thickness and total number of cells were decreased, while the numbers of TUNEL-positive neurons, caspase-3 activation were significantly increased compared with age-matched WT. Our results demonstrate that the olfactory system may get deteriorated before onset of AD symptoms. Our findings imply that an olfactory biopsy could be served as an early and relatively simple diagnostic tool for potential AD patients.

  1. Olfactory Ensheathing Cells Express α7 Integrin to Mediate Their Migration on Laminin

    PubMed Central

    Ingram, Norianne T.; Khankan, Rana R.; Phelps, Patricia E.

    2016-01-01

    The unique glia located in the olfactory system, called olfactory ensheathing cells (OECs), are implicated as an attractive choice for transplantation therapy following spinal cord injury because of their pro-regenerative characteristics. Adult OECs are thought to improve functional recovery and regeneration after injury by secreting neurotrophic factors and making cell-to-cell contacts with regenerating processes, but the mechanisms are not well understood. We show first that α7 integrin, a laminin receptor, is highly expressed at the protein level by OECs throughout the olfactory system, i.e., in the olfactory mucosa, olfactory nerve, and olfactory nerve layer of the olfactory bulb. Then we asked if OECs use the α7 integrin receptor directly to promote neurite outgrowth on permissive and neutral substrates, in vitro. We co-cultured α7+/+ and α7lacZ/lacZ postnatal cerebral cortical neurons with α7+/+ or α7lacZ/lacZ OECs and found that genotype did not effect the ability of OECs to enhance neurite outgrowth by direct contact. Loss of α7 integrin did however significantly decrease the motility of adult OECs in transwell experiments. Twice as many α7+/+ OECs migrated through laminin-coated transwells compared to α7+/+ OECs on poly-L-lysine (PLL). This is in contrast to α7lacZ/lacZ OECs, which showed no migratory preference for laminin substrate over PLL. These results demonstrate that OECs express α7 integrin, and that laminin and its α7 integrin receptor contribute to adult OEC migration in vitro and perhaps also in vivo. PMID:27078717

  2. Role of Nrf2 antioxidant defense in mitigating cadmium-induced oxidative stress in the olfactory system of zebrafish

    SciTech Connect

    Wang, Lu; Gallagher, Evan P.

    2013-01-15

    Exposure to trace metals can disrupt olfactory function in fish leading to a loss of behaviors critical to survival. Cadmium (Cd) is an olfactory toxicant that elicits cellular oxidative stress as a mechanism of toxicity while also inducing protective cellular antioxidant genes via activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. However, the molecular mechanisms of Cd-induced olfactory injury have not been characterized. In the present study, we investigated the role of the Nrf2-mediated antioxidant defense pathway in protecting against Cd-induced olfactory injury in zebrafish. A dose-dependent induction of Nrf2-regulated antioxidant genes associated with cellular responses to oxidative stress was observed in the olfactory system of adult zebrafish following 24 h Cd exposure. Zebrafish larvae exposed to Cd for 3 h showed increased glutathione S-transferase pi (gst pi), glutamate–cysteine ligase catalytic subunit (gclc), heme oxygenase 1 (hmox1) and peroxiredoxin 1 (prdx1) mRNA levels indicative of Nrf2 activation, and which were blocked by morpholino-mediated Nrf2 knockdown. The inhibition of antioxidant gene induction in Cd-exposed Nrf2 morphants was associated with disruption of olfactory driven behaviors, increased cell death and loss of olfactory sensory neurons (OSNs). Nrf2 morphants also exhibited a downregulation of OSN-specific genes after Cd exposure. Pre-incubation of embryos with sulforaphane (SFN) partially protected against Cd-induced olfactory tissue damage. Collectively, our results indicate that oxidative stress is an important mechanism of Cd-mediated injury in the zebrafish olfactory system. Moreover, the Nrf2 pathway plays a protective role against cellular oxidative damage and is important in maintaining zebrafish olfactory function. -- Highlights: ► Oxidative stress is an important mechanism of Cd-mediated olfactory injury. ► Cd induces antioxidant gene expression in the zebrafish olfactory system. ► The

  3. Olfactory sensitivity of Pacific Lampreys to lamprey bile acids

    USGS Publications Warehouse

    Robinson, T. Craig; Sorensen, Peter W.; Bayer, Jennifer M.; Seelye, James G.

    2009-01-01

    Pacific lampreys Lampetra tridentata are in decline throughout much of their historical range in the Columbia River basin. In support of restoration efforts, we tested whether larval and adult lamprey bile acids serve as migratory and spawning pheromones in adult Pacific lampreys, as they do in sea lampreys Petromyzon marinus. The olfactory sensitivity of adult Pacific lampreys to lamprey bile acids was measured by electro-olfactogram recording from the time of their capture in the spring until their spawning in June of the following year. As controls, we tested L-arginine and a non-lamprey bile acid, taurolithocholic acid 3-sulfate (TLS). Migrating adult Pacific lampreys were highly sensitive to petromyzonol sulfate (a component of the sea lamprey migratory pheromone) and 3-keto petromyzonol sulfate (a component of the sea lamprey sex pheromone) when first captured. This sensitivity persisted throughout their long migratory and overwinter holding period before declining to nearly unmeasurable levels by the time of spawning. The absolute magnitudes of adult Pacific lamprey responses to lamprey bile acids were smaller than those of the sea lamprey, and unlike the sea lamprey, the Pacific lamprey did not appear to detect TLS. No sexual dimorphism was noted in olfactory sensitivity. Thus, Pacific lampreys are broadly similar to sea lampreys in showing sensitivity to the major lamprey bile acids but apparently differ in having a longer period of sensitivity to those acids. The potential utility of bile acid-like pheromones in the restoration of Pacific lampreys warrants their further investigation in this species.

  4. Olfactory dysfunction, olfactory bulb pathology and urban air pollution

    PubMed Central

    Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; Henríquez-Roldán, Carlos; Osnaya, Norma; González-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderon, Rafael; Herritt, Lou; Brooks, Diane; Keefe, Sheyla; Palacios-Moreno, Juan; Villarreal-Calderon, Rodolfo; Torres-Jardón, Ricardo; Medina-Cortina, Humberto; Delgado-Chávez, Ricardo; Aiello-Mora, Mario; Maronpot, Robert R.; Doty, Richard L

    2010-01-01

    Mexico City (MC) residents are exposed to severe air pollution and exhibit olfactory bulb inflammation. We compared the olfactory function of individuals living under conditions of extreme air pollution to that of controls from a relatively clean environment and explore associations between olfaction scores, apolipoprotein E (APOE) status, and pollution exposure. The olfactory bulbs (OBs) of 35 MC and 9 controls 20.8 ± 8.5 y were assessed by light and electron microscopy. The University of Pennsylvania Smell Identification Test (UPSIT) was administered to 62 MC / 25 controls 21.2 ±2.7 y. MC subjects had significantly lower UPSIT scores: 34.24 ± 0.42 versus controls 35.76 ± 0.40, p=0.03. Olfaction deficits were present in 35.5% MC and 12% of controls. MC APOE ε 4 carriers failed 2.4 ± 0.54 items in the 10-item smell identification scale from the UPSIT related to Alzheimer's disease, while APOE 2/3 and 3/3 subjects failed 1.36 ± 0.16 items, p = 0.01. MC residents exhibited OB endothelial hyperplasia, neuronal accumulation of particles (2/35), and immunoreactivity to beta amyloid βA42 (29/35) and/or α-synuclein (4/35) in neurons, glial cells and/or blood vessels. Ultrafine particles were present in OBs endothelial cytoplasm and basement membranes. Control OBs were unremarkable. Air pollution exposure is associated with olfactory dysfunction and OB pathology, APOE 4 may confer greater susceptibility to such abnormalities, and ultrafine particles could play a key role in the OB pathology. This study contributes to our understanding of the influences of air pollution on olfaction and its potential contribution to neurodegeneration. PMID:19297138

  5. Anatomical and molecular consequences of Unilateral Naris Closure on two populations of olfactory sensory neurons expressing defined odorant receptors.

    PubMed

    Molinas, Adrien; Aoudé, Imad; Soubeyre, Vanessa; Tazir, Bassim; Cadiou, Hervé; Grosmaitre, Xavier

    2016-07-28

    Mammalian olfactory sensory neurons (OSNs), the primary elements of the olfactory system, are located in the olfactory epithelium lining the nasal cavity. Exposed to the environment, their lifespan is short. Consequently, OSNs are regularly regenerated and several reports show that activity strongly modulates their development and regeneration: the peripheral olfactory system can adjust to the amount of stimulus through compensatory mechanisms. Unilateral naris occlusion (UNO) was frequently used to investigate this mechanism at the entire epithelium level. However, there is little data regarding the effects of UNO at the cellular level, especially on individual neuronal populations expressing a defined odorant receptor. Here, using UNO during the first three postnatal weeks, we analyzed the anatomical and molecular consequences of sensory deprivation in OSNs populations expressing the MOR23 and M71 receptors. The density of MOR23-expressing neurons is decreased in the closed side while UNO does not affect the density of M71-expressing neurons. Using Real Time qPCR on isolated neurons, we observed that UNO modulates the transcript levels for transduction pathway proteins (odorant receptors, CNGA2, PDE1c). The transcripts modulated by UNO will differ between populations depending on the receptor expressed. These results suggest that sensory deprivation will have different effects on different OSNs' populations. As a consequence, early experience will shape the functional properties of OSNs differently depending on the type of odorant receptor they express.

  6. Cobalt Chloride Treatment Used to Ablate the Lateral Line System Also Impairs the Olfactory System in Three Freshwater Fishes

    PubMed Central

    Butler, Julie M.; Field, Karen E.; Maruska, Karen P.

    2016-01-01

    Fishes use multimodal signals during both inter- and intra-sexual displays to convey information about their sex, reproductive state, and social status. These complex behavioral displays can include visual, auditory, olfactory, tactile, and hydrodynamic signals, and the relative role of each sensory channel in these complex multi-sensory interactions is a common focus of neuroethology. The mechanosensory lateral line system of fishes detects near-body water movements and is implicated in a variety of behaviors including schooling, rheotaxis, social communication, and prey detection. Cobalt chloride is commonly used to chemically ablate lateral line neuromasts, thereby eliminating water-movement cues to test for mechanosensory-mediated behavioral functions. However, cobalt acts as a nonspecific calcium channel antagonist and could potentially disrupt function of all superficially located sensory receptor cells, including those for chemosensing. Here, we examined whether CoCl2 treatment used to ablate the lateral line system also impairs olfaction in three freshwater fishes, the African cichlid fish Astatotilapia burtoni, goldfish Carassius auratus, and the Mexican blind cavefish Astyanax mexicanus. To examine the impact of CoCl2 on the activity of peripheral receptors, we quantified DASPEI fluorescence intensity of the olfactory epithelium from fish exposed to control and CoCl2 solutions. In addition, we examined brain activation in olfactory processing regions of A. burtoni immersed in either control or cobalt solutions. All three species exposed to CoCl2 had decreased DASPEI staining of the olfactory epithelium, and in A. burtoni, cobalt treatment caused reduced neural activation in olfactory processing regions of the brain. To our knowledge this is the first empirical evidence demonstrating that the same CoCl2 treatment used to ablate the lateral line system also impairs olfactory function. These data have important implications for the use of CoCl2 in future

  7. Identification and localisation of glycoconjugates in the olfactory mucosa of the armadillo Chaetophractus villosus

    PubMed Central

    FERRARI, C. C.; CARMANCHAHI, P. D.; ALDANA MARCOS, H. J.; MUGNAINI, M. T.; AFFANNI, J. M.; PAZ, D. A.

    1999-01-01

    Conventional histochemistry and the binding patterns of 22 biotinylated lectins were examined for characterisation of glycoconjugates in the components of the olfactory mucosa of the armadillo Chaetophractus villosus. The mucous lining the olfactory epithelium showed binding sites for DSL, WGA, STL, LEL, PHA-E and JAC. Only the basilar processes of the supporting cells stained for Con-A and S-Con A. The olfactory receptor neurons stained with LEL, LCA, Con A, S-Con A, JAC and PNA. The layer of basal cells did not react with any of the lectins studied. Bowman's glands in the lamina propria showed subpopulations of acinar cells reacting with SBA, S-WGA, WGA, STL, Con A, PSA, PNA, SJA, VVA, JAC and S-Con A, but in our optical studies with lectins we were unable to differentiate between mucous and serous cells in the way that is possible on electron microscopy. The ducts of Bowman's glands were labelled with S-WGA, STL, LEL, PHA-E, BSL-I and JAC. This histochemical study on the glycoconjugates of the olfactory mucosa in the order Xenarthra provides a basis for further experimental investigations. PMID:10386777

  8. Modulatory Effects of Sex Steroids Progesterone and Estradiol on Odorant Evoked Responses in Olfactory Receptor Neurons

    PubMed Central

    Scholz, Paul; Mohrhardt, Julia; Gisselmann, Günter; Hatt, Hanns

    2016-01-01

    The influence of the sex steroid hormones progesterone and estradiol on physiology and behavior during menstrual cycles and pregnancy is well known. Several studies indicate that olfactory performance changes with cyclically fluctuating steroid hormone levels in females. Knowledge of the exact mechanisms behind how female sex steroids modulate olfactory signaling is limited. A number of different known genomic and non-genomic actions that are mediated by progesterone and estradiol via interactions with different receptors may be responsible for this modulation. Next generation sequencing-based RNA-Seq transcriptome data from the murine olfactory epithelium (OE) and olfactory receptor neurons (ORNs) revealed the expression of several membrane progestin receptors and the estradiol receptor Gpr30. These receptors are known to mediate rapid non-genomic effects through interactions with G proteins. RT-PCR and immunohistochemical staining results provide evidence for progestin and estradiol receptors in the ORNs. These data support the hypothesis that steroid hormones are capable of modulating the odorant-evoked activity of ORNs. Here, we validated this hypothesis through the investigation of steroid hormone effects by submerged electro-olfactogram and whole cell patch-clamp recordings of ORNs. For the first time, we demonstrate that the sex steroid hormones progesterone and estradiol decrease odorant-evoked signals in the OE and ORNs of mice at low nanomolar concentrations. Thus, both of these sex steroids can rapidly modulate the odor responsiveness of ORNs through membrane progestin receptors and the estradiol receptor Gpr30. PMID:27494699

  9. EMX2 protein in the developing mouse brain and olfactory area.

    PubMed

    Mallamaci, A; Iannone, R; Briata, P; Pintonello, L; Mercurio, S; Boncinelli, E; Corte, G

    1998-10-01

    The distribution of EMX2, the protein product of the homeobox gene Emx2, was analyzed in the developing mouse CNS by means of a polyclonal antibody we raised against it. The protein is present in the rostral brain, the olfactory area and a set of scattered cells lying between the nasal pits and the telencephalon. In the cortical neuroepithelium EMX2 is expressed all along the rostro-caudal axis in a graded distribution with a caudal-medial maximum and a rostral-lateral minimum. Anti-EMX2 immunoreactivity is also detectable in Cajal-Retzius cells as well as in apical dendrites of marginal neurons of the cortical plate. We also observe that the EMX2 and EMX1 homeoproteins display complementary expression patterns in olfactory bulbs and amygdaloid complex. Here, they demarcate different neuronal populations, involved in processing olfactory information coming from the vomero-nasal organ and from the main olfactory epithelium, respectively. EMX2 is also detectable in mesencephalic structures, such as the optic tectum and tegmentum. The graded distribution of EMX2 along antero-posterior and medial-lateral axes of the primitive cortex prefigures a role of this protein in the subdivision of the cortex in cytoarchitectonic regions and possibly functional areas, whereas its presence in Cajal-Retzius cells suggests a role in the process of cortical lamination.

  10. Odor-evoked gene regulation and visualization in olfactory receptor neurons

    PubMed Central

    Bennett, Mosi K.; Kulaga, Heather M.; Reed, Randall R.

    2010-01-01

    Odorant-evoked activity contributes to olfactory epithelium organization and axon targeting. We examined the consequences on gene expression of a genetic disruption of the channel responsible for olfactory transduction. Genes encoding calcium-binding EF-hand motifs, were among the most highly regulated transcripts consistent with the central role of Ca2+ influx in neuronal depolarization. Several genes encoding integral membrane proteins are also highly regulated. One gene, Lrrc3b, was regulated more than 10-fold by odorant activity. Changes in expression occur within thirty minutes and are maintained for several hours. In genetic disruptions of Lrrc3b, a Lrrc3b-promoter-driven reporter adopts the activity-regulated expression of the endogenous gene. Individual olfactory glomeruli have a wide spectrum of activity levels that can be modulated by altering odor exposure. The Lrrc3b reporter mouse permits direct assessment of activity in identified glomeruli. In stable odorant environments, activity-regulated proteins provide a characteristic signature that is correlated with the olfactory receptor they express. PMID:20080187

  11. Transcriptional responses in the rat nasal epithelium following subchronic inhalation of naphthalene vapor

    SciTech Connect

    Clewell, H.J. Efremenko, A.; Campbell, J.L.; Dodd, D.E.; Thomas, R.S.

    2014-10-01

    Male and female Fischer 344 rats were exposed to naphthalene vapors at 0 (controls), 0.1, 1, 10, and 30 ppm for 6 h/d, 5 d/wk, over a 90-day period. Following exposure, the respiratory epithelium and olfactory epithelium from the nasal cavity were dissected separately, RNA was isolated, and gene expression microarray analysis was conducted. Only a few significant gene expression changes were observed in the olfactory or respiratory epithelium of either gender at the lowest concentration (0.1 ppm). At the 1.0 ppm concentration there was limited evidence of an oxidative stress response in the respiratory epithelium, but not in the olfactory epithelium. In contrast, a large number of significantly enriched cellular pathway responses were observed in both tissues at the two highest concentrations (10 and 30 ppm, which correspond to tumorigenic concentrations in the NTP bioassay). The nature of these responses supports a mode of action involving oxidative stress, inflammation and proliferation. These results are consistent with a dose-dependent transition in the mode of action for naphthalene toxicity/carcinogenicity between 1.0 and 10 ppm in the rat. In the female olfactory epithelium (the gender/site with the highest incidences of neuroblastomas in the NTP bioassay), the lowest concentration at which any signaling pathway was significantly affected, as characterized by the median pathway benchmark dose (BMD) or its 95% lower bound (BMDL) was 6.0 or 3.7 ppm, respectively, while the lowest female olfactory BMD values for pathways related to glutathione homeostasis, inflammation, and proliferation were 16.1, 11.1, and 8.4 ppm, respectively. In the male respiratory epithelium (the gender/site with the highest incidences of adenomas in the NTP bioassay), the lowest pathway BMD and BMDL were 0.4 and 0.3 ppm, respectively, and the lowest male respiratory BMD values for pathways related to glutathione homeostasis, inflammation, and proliferation were 0.5, 0.7, and 0.9 ppm

  12. Does iron deficiency anemia affect olfactory function?

    PubMed

    Dinc, Mehmet Emre; Dalgic, Abdullah; Ulusoy, Seckin; Dizdar, Denizhan; Develioglu, Omer; Topak, Murat

    2016-07-01

    Conclusion This study found a negative effect of IDA on olfactory function. IDA leads to a reduction in olfactory function, and decreases in hemoglobin levels result in further reduction in olfactory function. Objective This study examined the effects of iron-deficiency anemia (IDA) on olfactory function. Method The study enrolled 50 IDA patients and 50 healthy subjects. Olfactory function was evaluated using the Sniffin' Sticks olfactory test. The diagnosis of IDA was made according to World Health Organization (WHO) criteria. Results Patients with IDA had a significantly lower threshold, discrimination, and identification (TDI) value, and a lower threshold compared with the control group. However, there were no significant differences between the groups in terms of smell selectivity values.

  13. Olfactory neuroblastoma: A case report

    PubMed Central

    USLU, GONCA HANEDAN; CANYILMAZ, EMINE; ZENGIN, AHMET YASAR; MUNGAN, SEVDEGUL; YONEY, ADNAN; BAHADIR, OSMAN; GOCMEZ, HUSEYIN

    2015-01-01

    Olfactory neuroblastoma (ON) is a rare type of malignant neoplasm originating from the olfactory neuroepithelial cells of the nasal cavity. ON is also known as esthesioneuroblastoma or neuroendocrine carcinoma. The malignancy accounts for <3% of tumors originating in the nasal cavity. Through the nasal cavity, ON may infiltrate the sinuses, the orbit and the cranium. The tumor is characterized by a pattern of slow growth and local recurrences. Treatment options are surgical excision or surgery combined with a radiotherapy (RT) and/or chemotherapy combination treatment. The present study reports the case of a 69-year-old patient with a mass in the nasal cavity who was treated by combined surgical excision and RT. The literature for ON and the treatment of the tumor are also discussed. PMID:26788185

  14. Insight of scent: experimental evidence of olfactory capabilities in the wandering albatross (Diomedea exulans).

    PubMed

    Mardon, J; Nesterova, A P; Traugott, J; Saunders, S M; Bonadonna, F

    2010-02-15

    Wandering albatrosses routinely forage over thousands of kilometres of open ocean, but the sensory mechanisms used in the food search itself have not been completely elucidated. Recent telemetry studies show that some spatial behaviours of the species are consistent with the 'multimodal foraging strategy' hypothesis which proposes that birds use a combination of olfactory and visual cues while foraging at sea. The 'multimodal foraging strategy' hypothesis, however, still suffers from a lack of experimental evidence, particularly regarding the olfactory capabilities of wandering albatrosses. As an initial step to test the hypothesis, we carried out behavioural experiments exploring the sensory capabilities of adult wandering albatrosses at a breeding colony. Three two-choice tests were designed to investigate the birds' response to olfactory and visual stimuli, individually or in combination. Perception of the different stimuli was assessed by comparing the amount of exploration directed towards an 'experimental' display or a 'control' display. Our results indicate that birds were able to perceive the three types of stimulus presented: olfactory, visual and combined. Moreover, olfactory and visual cues were found to have additional effects on the exploratory behaviours of males. This simple experimental demonstration of reasonable olfactory capabilities in the wandering albatross supports the 'multimodal foraging strategy' and is consistent with recent hypotheses of the evolutionary history of procellariiforms.

  15. Identification of accessory olfactory system and medial amygdala in the zebrafish

    PubMed Central

    Biechl, Daniela; Tietje, Kristin; Ryu, Soojin; Grothe, Benedikt; Gerlach, Gabriele; Wullimann, Mario F.

    2017-01-01

    Zebrafish larvae imprint on visual and olfactory cues of their kin on day 5 and 6 postfertilization, respectively. Only imprinted (but not non-imprinted) larvae show strongly activated crypt (and some microvillous) cells demonstrated by pERK levels after subsequent exposure to kin odor. Here, we investigate the olfactory bulb of zebrafish larvae for activated neurons located at the sole glomerulus mdG2 which receives crypt cell input. Imprinted larvae show a significantly increased activation of olfactory bulb cells compared to non-imprinted larvae after exposure to kin odor. Surprisingly, pERK activated Orthopedia-positive cell numbers in the intermediate ventral telencephalic nucleus were higher in non-imprinted, kin odor stimulated larvae compared to control and to kin-odor stimulated imprinted larvae and control. Moreover, DiI tracing experiments in adult zebrafish show a neuronal circuit from crypt/microvillous olfactory sensory neurons via dorsomedial olfactory bulb and intermediate ventral telencephalic nucleus (thus, arguably the teleostean medial amygdala) to tuberal hypothalamus, demonstrating for the first time an accessory olfactory system in teleosts. PMID:28290515

  16. Disease stabilization of progressive olfactory neuroblastoma (esthesioneuroblastoma) under treatment with sunitinib mesylate.

    PubMed

    Preusser, M; Hutterer, M; Sohm, M; Koperek, O; Elandt, K; Dieckmann, K; Prayer, D; Marosi, C

    2010-04-01

    Olfactory neuroblastoma (esthesioneuroblastoma) is a rare neoplasm of the olfactory epithelium in the upper nasal cavity. Here, we report the case of a 69-year-old man who presented with massive progression of a metastatic esthesioneuroblastoma after endonasal resection, functional neck dissection, and radiotherapy of local and distant tumor relapses. After exhaustion of all conventional therapeutic options, we initiated treatment with the oral multityrosinekinase inhibitor sunitinib mesylate. Using this drug, significant improvement of clinical symptoms, disease stabilization, and recovery from Karnofsky index of 40% to 70% could be achieved in the absence of significant adverse drug effects. The patient died 15 months after initiation of sunitinib therapy due to complications of a traumatic femoral neck fracture without evidence of tumor progression. Immunohistochemical analysis of tumor tissue specimens obtained at initial surgery revealed ample expression of platelet-derived growth factor receptor (PDGFR)-b on stromal and endothelial cells. Sunitinib should be considered for palliative therapy of advanced esthesioneuroblastoma.

  17. Role of Centrifugal Projections to the Olfactory Bulb in Olfactory Processing

    ERIC Educational Resources Information Center

    Kiselycznyk, Carly L.; Zhang, Steven; Linster, Christine

    2006-01-01

    While there is evidence that feedback projections from cortical and neuromodulatory structures to the olfactory bulb are crucial for maintaining the oscillatory dynamics of olfactory bulb processing, it is not clear how changes in dynamics are related to odor perception. Using electrical lesions of the olfactory peduncle, sparing output from the…

  18. Linking local circuit inhibition to olfactory behavior: a critical role for granule cells in olfactory discrimination.

    PubMed

    Strowbridge, Ben W

    2010-02-11

    In this issue of Neuron, Abraham et al. report a direct connection between inhibitory function and olfactory behavior. Using molecular methods to alter glutamate receptor subunit composition in olfactory bulb granule cells, the authors found a selective modulation in the time required for difficult, but not simple, olfactory discrimination tasks.

  19. Drosophila Avoids Parasitoids by Sensing Their Semiochemicals via a Dedicated Olfactory Circuit

    PubMed Central

    Ebrahim, Shimaa A. M.; Dweck, Hany K. M.; Stökl, Johannes; Hofferberth, John E.; Trona, Federica; Weniger, Kerstin; Rybak, Jürgen; Seki, Yoichi; Stensmyr, Marcus C.; Sachse, Silke; Hansson, Bill S.; Knaden, Markus

    2015-01-01

    Detecting danger is one of the foremost tasks for a neural system. Larval parasitoids constitute clear danger to Drosophila, as up to 80% of fly larvae become parasitized in nature. We show that Drosophila melanogaster larvae and adults avoid sites smelling of the main parasitoid enemies, Leptopilina wasps. This avoidance is mediated via a highly specific olfactory sensory neuron (OSN) type. While the larval OSN expresses the olfactory receptor Or49a and is tuned to the Leptopilina odor iridomyrmecin, the adult expresses both Or49a and Or85f and in addition detects the wasp odors actinidine and nepetalactol. The information is transferred via projection neurons to a specific part of the lateral horn known to be involved in mediating avoidance. Drosophila has thus developed a dedicated circuit to detect a life-threatening enemy based on the smell of its semiochemicals. Such an enemy-detecting olfactory circuit has earlier only been characterized in mice and nematodes. PMID:26674493

  20. Inactivation of the olfactory marker protein (OMP) gene in river dolphins and other odontocete cetaceans.

    PubMed

    Springer, Mark S; Gatesy, John

    2017-04-01

    Various toothed whales (Odontoceti) are unique among mammals in lacking olfactory bulbs as adults and are thought to be anosmic (lacking the olfactory sense). At the molecular level, toothed whales have high percentages of pseudogenic olfactory receptor genes, but species that have been investigated to date retain an intact copy of the olfactory marker protein gene (OMP), which is highly expressed in olfactory receptor neurons and may regulate the temporal resolution of olfactory responses. One hypothesis for the retention of intact OMP in diverse odontocete lineages is that this gene is pleiotropic with additional functions that are unrelated to olfaction. Recent expression studies provide some support for this hypothesis. Here, we report OMP sequences for representatives of all extant cetacean families and provide the first molecular evidence for inactivation of this gene in vertebrates. Specifically, OMP exhibits independent inactivating mutations in six different odontocete lineages: four river dolphin genera (Platanista, Lipotes, Pontoporia, Inia), sperm whale (Physeter), and harbor porpoise (Phocoena). These results suggest that the only essential role of OMP that is maintained by natural selection is in olfaction, although a non-olfactory role for OMP cannot be ruled out for lineages that retain an intact copy of this gene. Available genome sequences from cetaceans and close outgroups provide evidence of inactivating mutations in two additional genes (CNGA2, CNGA4), which imply further pseudogenization events in the olfactory cascade of odontocetes. Selection analyses demonstrate that evolutionary constraints on all three genes (OMP, CNGA2, CNGA4) have been greatly reduced in Odontoceti, but retain a signature of purifying selection on the stem Cetacea branch and in Mysticeti (baleen whales). This pattern is compatible with the 'echolocation-priority' hypothesis for the evolution of OMP, which posits that negative selection was maintained in the common

  1. Mucus trail tracking in a predatory snail: olfactory processing retooled to serve a novel sensory modality

    PubMed Central

    Patel, Kinjal; Shaheen, Nagma; Witherspoon, Jessica; Robinson, Natallia; Harrington, Melissa A

    2014-01-01

    Introduction The rosy wolfsnail (Euglandina rosea), a predatory land snail, finds prey snails and potential mates by following their mucus trails. Euglandina have evolved unique, mobile lip extensions that detect mucus and aid in following trails. Currently, little is known of the neural substrates of the trail-following behavior. Methods To investigate the neural correlates of trail following we used tract-tracing experiments in which nerves were backfilled with either nickel-lysine or Lucifer yellow, extracellular recording of spiking neurons in snail procerebra using a multielectrode array, and behavioral assays of trail following and movement toward the source of a conditioned odor. Results The tract-tracing experiments demonstrate that in Euglandina, the nerves carrying mucus signals innervate the same region of the central ganglia as the olfactory nerves, while the electrophysiology studies show that mucus stimulation of the sensory epithelium on the lip extensions alters the frequency and pattern of neural activity in the procerebrum in a manner similar to odor stimulation of the olfactory epithelium on the optic tentacles of another land snail species, Cantareus aspersa (previously known as Helix aspersa). While Euglandina learn to follow trails of novel chemicals that they contact with their lip extensions in one to three trials, these snails proved remarkably resistant to associative learning in the olfactory modality. Even after seven to nine pairings of odorant molecules with food, they showed no orientation toward the conditioned odor. This is in marked contrast to Cantareus snails, which reliably oriented toward conditioned odors after two to three trials. Conclusions The apparent inability of Euglandina to learn to associate food with odors and use odor cues to drive behavior suggests that the capability for sophisticated neural processing of nonvolatile mucus cues detected by the lip extensions has evolved at the expense of processing of odorant

  2. Timberol® Inhibits TAAR5-Mediated Responses to Trimethylamine and Influences the Olfactory Threshold in Humans

    PubMed Central

    Wallrabenstein, Ivonne; Singer, Marco; Panten, Johannes; Hatt, Hanns; Gisselmann, Günter

    2015-01-01

    In mice, trace amine-associated receptors (TAARs) are interspersed in the olfactory epithelium and constitute a chemosensory subsystem that is highly specific for detecting volatile amines. Humans possess six putative functional TAAR genes. Human TAAR5 (hTAAR5) is highly expressed in the olfactory mucosa and was shown to be specifically activated by trimethylamine. In this study, we were challenged to uncover an effective blocker substance for trimethylamine-induced hTAAR5 activation. To monitor blocking effects, we recombinantly expressed hTAAR5 and employed a commonly used Cre-luciferase reporter gene assay. Among all tested potential blocker substances, Timberol®, an amber-woody fragrance, is able to inhibit the trimethylamine-induced hTAAR5 activation up to 96%. Moreover, human psychophysical data showed that the presence of Timberol® increases the olfactory detection threshold for the characteristic fishy odor of trimethylamine by almost one order of magnitude. In conclusion, our results show that among tested receptors Timberol® is a specific and potent antagonist for the hTAAR5-mediated response to trimethylamine in a heterologous system. Furthermore, our data concerning the observed shift of the olfactory detection threshold in vivo implicate that hTAAR5 or other receptors that may be inhibited by Timberol® could be involved in the high affinity olfactory perception of trimethylamine in humans. PMID:26684881

  3. The 'de novo' DNA methyltransferase Dnmt3b compensates the Dnmt1-deficient intestinal epithelium.

    PubMed

    Elliott, Ellen N; Sheaffer, Karyn L; Kaestner, Klaus H

    2016-01-25

    Dnmt1 is critical for immediate postnatal intestinal development, but is not required for the survival of the adult intestinal epithelium, the only rapidly dividing somatic tissue for which this has been shown. Acute Dnmt1 deletion elicits dramatic hypomethylation and genomic instability. Recovery of DNA methylation state and intestinal health is dependent on the de novo methyltransferase Dnmt3b. Ablation of both Dnmt1 and Dnmt3b in the intestinal epithelium is lethal, while deletion of either Dnmt1 or Dnmt3b has no effect on survival. These results demonstrate that Dnmt1 and Dnmt3b cooperate to maintain DNA methylation and genomic integrity in the intestinal epithelium.

  4. Study of orexins signal transduction pathways in rat olfactory mucosa and in olfactory sensory neurons-derived cell line Odora: multiple orexin signalling pathways.

    PubMed

    Gorojankina, Tatiana; Grébert, Denise; Salesse, Roland; Tanfin, Zahra; Caillol, Monique

    2007-06-07

    Orexins A and B (OxA and OxB) are multifunctional neuropeptides implicated in the regulation of energy metabolism, wakefulness but also in a broad range of motivated behaviours. They signal through two G-protein-coupled receptors: orexin receptor 1 and 2 (Ox1R and Ox2R). The orexins and their receptors are present at all levels of the rat olfactory system: epithelium, bulb, piriform cortex but their signalling mechanisms remain unknown. We have studied orexins signal transduction pathways in the rat olfactory mucosa (OM) and in the Odora cell line derived from olfactory sensory neurons and heterologously expressing Ox1R or Ox2R. We have demonstrated by western blot and RT-PCR that multiple components of adenylyl cyclase (AC) and phospholipase C (PLC) signalling pathways were identical in OM and Odora cells. OxA and OxB induced a weak increase in IP3 in OM; they induced a significant rise in cAMP and IP3 in Odora transfected cells, suggesting the activation of AC and PLC pathways. Both OxA and OxB induced intracellular calcium elevation and transient activation of MAP kinases (ERK42/44) in Odora/Ox1R and Odora/Ox2R cells. These results suggest the existence of multiple orexins signalling pathways in Odora cells and probably in OM, corresponding to different possible roles of these peptides.

  5. Channel properties of the splicing isoforms of the olfactory calcium-activated chloride channel Anoctamin 2

    PubMed Central

    Ponissery Saidu, Samsudeen; Stephan, Aaron B.; Talaga, Anna K.

    2013-01-01

    Anoctamin (ANO)2 (or TMEM16B) forms a cell membrane Ca2+-activated Cl− channel that is present in cilia of olfactory receptor neurons, vomeronasal microvilli, and photoreceptor synaptic terminals. Alternative splicing of Ano2 transcripts generates multiple variants with the olfactory variants skipping exon 14 and having alternative splicing of exon 4. In the present study, 5′ rapid amplification of cDNA ends analysis was conducted to characterize the 5′ end of olfactory Ano2 transcripts, which showed that the most abundant Ano2 transcripts in the olfactory epithelium contain a novel starting exon that encodes a translation initiation site, whereas transcripts of the publically available sequence variant, which has an alternative and longer 5′ end, were present in lower abundance. With two alternative starting exons and alternative splicing of exon 4, four olfactory ANO2 isoforms are thus possible. Patch-clamp experiments in transfected HEK293T cells expressing these isoforms showed that N-terminal sequences affect Ca2+ sensitivity and that the exon 4–encoded sequence is required to form functional channels. Coexpression of the two predominant isoforms, one with and one without the exon 4 sequence, as well as coexpression of the two rarer isoforms showed alterations in channel properties, indicating that different isoforms interact with each other. Furthermore, channel properties observed from the coexpression of the predominant isoforms better recapitulated the native channel properties, suggesting that the native channel may be composed of two or more splicing isoforms acting as subunits that together shape the channel properties. PMID:23669718

  6. Calcium signals in olfactory neurons.

    PubMed

    Tareilus, E; Noé, J; Breer, H

    1995-11-09

    Laser scanning confocal microscopy in combination with the fluorescent calcium indicators Fluo-3 and Fura-Red was employed to estimate the intracellular concentration of free calcium ions in individual olfactory receptor neurons and to monitor temporal and spatial changes in the Ca(2+)-level upon stimulation. The chemosensory cells responded to odorants with a significant increase in the calcium concentration, preferentially in the dendritic knob. Applying various stimulation paradigma, it was found that in a population of isolated cells, subsets of receptor neurons display distinct patterns of responsiveness.

  7. Neuromodulation of olfactory sensitivity in the peripheral olfactory organs of the American cockroach, Periplaneta americana.

    PubMed

    Jung, Je Won; Kim, Jin-Hee; Pfeiffer, Rita; Ahn, Young-Joon; Page, Terry L; Kwon, Hyung Wook

    2013-01-01

    Olfactory sensitivity exhibits daily fluctuations. Several studies have suggested that the olfactory system in insects is modulated by both biogenic amines and neuropeptides. However, molecular and neural mechanisms underlying olfactory modulation in the periphery remain unclear since neuronal circuits regulating olfactory sensitivity have not been identified. Here, we investigated the structure and function of these signaling pathways in the peripheral olfactory system of the American cockroach, Periplaneta americana, utilizing in situ hybridization, qRT-PCR, and electrophysiological approaches. We showed that tachykinin was co-localized with the octopamine receptor in antennal neurons located near the antennal nerves. In addition, the tachykinin receptor was found to be expressed in most of the olfactory receptor neurons in antennae. Functionally, the effects of direct injection of tachykinin peptides, dsRNAs of tachykinin, tachykinin receptors, and octopamine receptors provided further support for the view that both octopamine and tachykinin modulate olfactory sensitivity. Taken together, these findings demonstrated that octopamine and tachykinin in antennal neurons are olfactory regulators in the periphery. We propose here the hypothesis that octopamine released from neurons in the brain regulates the release of tachykinin from the octopamine receptor neurons in antennae, which in turn modulates the olfactory sensitivity of olfactory receptor neurons, which house tachykinin receptors.

  8. A Closer Look at Acid-Base Olfactory Titrations

    ERIC Educational Resources Information Center

    Neppel, Kerry; Oliver-Hoyo, Maria T.; Queen, Connie; Reed, Nicole

    2005-01-01

    Olfactory titrations using raw onions and eugenol as acid-base indicators are reported. An in-depth investigation on olfactory titrations is presented to include requirements for potential olfactory indicators and protocols for using garlic, onions, and vanillin as acid-base olfactory indicators are tested.

  9. 21 CFR 874.1600 - Olfactory test device.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Diagnostic Devices § 874.1600 Olfactory test device. (a) Identification. An olfactory test device is used to determine whether an olfactory loss is present. The device... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Olfactory test device. 874.1600 Section...

  10. 21 CFR 874.1600 - Olfactory test device.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Diagnostic Devices § 874.1600 Olfactory test device. (a) Identification. An olfactory test device is used to determine whether an olfactory loss is present. The device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Olfactory test device. 874.1600 Section...

  11. Detection of Olfactory Dysfunction Using Olfactory Event Related Potentials in Young Patients with Multiple Sclerosis

    PubMed Central

    Caminiti, Fabrizia; De Salvo, Simona; De Cola, Maria Cristina; Russo, Margherita; Bramanti, Placido; Marino, Silvia; Ciurleo, Rosella

    2014-01-01

    Background Several studies reported olfactory dysfunction in patients with multiple sclerosis. The estimate of the incidence of olfactory deficits in multiple sclerosis is uncertain; this may arise from different testing methods that may be influenced by patients' response bias and clinical, demographic and cognitive features. Aims To evaluate objectively the olfactory function using Olfactory Event Related Potentials. Materials and Methods We tested the olfactory function of 30 patients with relapsing remitting multiple sclerosis (mean age of 36.03±6.96 years) and of 30 age, sex and smoking–habit matched healthy controls by using olfactory potentials. A selective and controlled stimulation of the olfactory system to elicit the olfactory event related potentials was achieved by a computer-controlled olfactometer linked directly with electroencephalograph. Relationships between olfactory potential results and patients' clinical characteristics, such as gender, disability status score, disease-modifying therapy, and disease duration, were evaluated. Results Seven of 30 patients did not show olfactory event related potentials. Sixteen of remaining 23 patients had a mean value of amplitude significantly lower than control group (p<0.01). The presence/absence of olfactory event related potentials was associated with dichotomous expanded disability status scale (p = 0.0433), as well as inversely correlated with the disease duration (r = −0.3641, p = 0.0479). Conclusion Unbiased olfactory dysfunction of different severity found in multiple sclerosis patients suggests an organic impairment which could be related to neuroinflammatory and/or neurodegenerative processes of olfactory networks, supporting the recent findings on neurophysiopathology of disease. PMID:25047369

  12. Expression of olfactory receptors in different life stages and life histories of wild Atlantic salmon (Salmo salar).

    PubMed

    Johnstone, K A; Lubieniecki, K P; Koop, B F; Davidson, W S

    2011-10-01

    It has been hypothesized that salmonids use olfactory cues to return to their natal rivers and streams. However, the key components of the molecular pathway involved in imprinting and homing are still unknown. If odorants are involved in salmon homing migration, then olfactory receptors should play a critical role in the dissipation of information from the environment to the fish. Therefore, we examined the expression profiles of a suite of genes encoding olfactory receptors and other olfactory-related genes in the olfactory rosettes of different life stages in two anadromous and one non-anadromous wild Atlantic salmon populations from Newfoundland, Canada. We identified seven differentially expressed OlfC genes in juvenile anadromous salmon compared to returning adults in both populations of anadromous Atlantic salmon. The salmon from the Campbellton River had an additional 10 genes that were differentially expressed in juveniles compared to returning adults. There was no statistically significant difference in gene expression of any of the genes in the non-anadromous population (P < 0.01). The function of the OlfC gene products is not clear, but they are predicted to be amino acid receptors. Other studies have suggested that salmon use amino acids for imprinting and homing. This study, the first to examine the expression of olfactory-related genes in wild North American Atlantic salmon, has identified seven OlfC genes that may be involved in the imprinting and homeward migration of anadromous Atlantic salmon.

  13. Preliminary Modeling and Simulation Study on Olfactory Cell Sensation

    SciTech Connect

    Zhou Jun; Chen Peihua; Liu Qingjun; Wang Ping; Yang Wei

    2009-05-23

    This paper introduced olfactory sensory neuron's whole-cell model with a concrete voltage-gated ionic channels and simulation. Though there are many models in olfactory sensory neuron and olfactory bulb, it remains uncertain how they express the logic of olfactory information processing. In this article, the olfactory neural network model is also introduced. This model specifies the connections among neural ensembles of the olfactory system. The simulation results of the neural network model are consistent with the observed olfactory biological characteristics such as 1/f-type power spectrum and oscillations.

  14. Reproductive responses to photoperiod persist in olfactory bulbectomized Siberian hamsters (Phodopus sungorus).

    PubMed

    Prendergast, Brian J; Pyter, Leah M; Galang, Jerome; Kay, Leslie M

    2009-03-02

    In reproductively photoperiodic Syrian hamsters, removal of the olfactory bulbs (OBx) leads to a marked and sustained increase in gonadotrophin secretion which prevents normal testicular regression in short photoperiods. In contrast, among reproductively nonphotoperiodic laboratory strains of rats and mice, bulbectomy unmasks reproductive responses to photoperiod. The role of the olfactory bulbs has been proposed to have opposite effects on responsiveness to photoperiod, depending on the photoperiodicity of the reproductive system; however, Syrian hamsters are the only reproductively photoperiodic rodent species for which the role of the olfactory bulb in reproductive endocrinology has been assessed. This experiment evaluated the role of the olfactory bulbs in the photoperiodic control of reproduction in Siberian hamsters (Phodopus sungorus), an established model species for the study of neural substrates mediating seasonality. Relative to control hamsters housed in long days (15 h light/day), exposure of adult male hamsters to short days (9h light/day) for 8 weeks led to a temporal expansion of the pattern of nocturnal locomotor activity, testicular regression, decreases in testosterone (T) production, and undetectable levels of plasma follicle-stimulating hormone (FSH). Bilateral olfactory bulbectomy failed to affect any of these responses to short days. The patterns of entrainment to long and short days suggests that pre-pineal mechanisms involved in photoperiodic timekeeping are functioning normally in OBx hamsters. The absence of increases in FSH following bulbectomy in long days is incompatible with the hypothesis that the olfactory bulbs provide tonic inhibition of the HPG axis in this species. In marked contrast to Syrian hamsters, the olfactory bulbs of Siberian hamsters play essentially no role in the modulation of tonic gonadotrophin production or gonadotrophin responses to photoperiod.

  15. Dopaminergic Neurones in the Main Olfactory Bulb: An Overview from an Electrophysiological Perspective

    PubMed Central

    Pignatelli, Angela; Belluzzi, Ottorino

    2017-01-01

    The olfactory bulb (OB), the first center processing olfactory information, is characterized by a vigorous life-long activity-dependent plasticity responsible for a variety of odor-evoked behavioral responses. It hosts the more numerous group of dopaminergic (DA) neurones in the central nervous system, cells strategically positioned at the entry of the bulbar circuitry, directly in contact with the olfactory nerve terminals, which play a key role in odor processing and in the adaptation of the bulbar network to external conditions. Here, we focus mainly on the electrophysiological properties of DA interneurones, reviewing findings concerning their excitability profiles in adulthood and in different phases of adult neurogenesis. We also discuss dynamic changes of the DA interneurones related to environmental stimuli and their possible functional implications. PMID:28261065

  16. Anxiety- and depressive-like behaviors in olfactory deficient Cnga2 knockout mice.

    PubMed

    Chen, Yanmei; Liu, Xiaofen; Jia, Xianglei; Zong, Wei; Ma, Yuanye; Xu, Fuqiang; Wang, Jianhong

    2014-12-15

    There is a close neuroanatomical connection between odor and emotional processing. Olfactory dysfunction is found in various neurodegenerative and neuropsychiatric disorders. Here, mice take the cyclic nucleotide gated channel 2 mutant gene (Cnga2), which is critical for olfactory sensory neurons to generate odor induced action potentials were used. The Cnga2 mice were congenitally anosmic. Adult mice were tested in a series behavioral paradigm such as open field, light/dark box, forced swim test and Y-maze. Our study found that Cnga2 mice showed increased anxiety- and depressive-like behaviors than their wide type siblings. However, Cnga2 mice showed no difference from the wide types when tested in the two-trial recognition Y-maze. The results indicate that innate olfactory deficiency might modulate emotional behaviors in mice.

  17. [Odor sensing system and olfactory display].

    PubMed

    Nakamoto, Takamichi

    2014-01-01

    In this review, an odor sensing system and an olfactory display are introduced into people in pharmacy. An odor sensing system consists of an array of sensors with partially overlapping specificities and pattern recognition technique. One of examples of odor sensing systems is a halitosis sensor which quantifies the mixture composition of three volatile sulfide compounds. A halitosis sensor was realized using a preconcentrator to raise sensitivity and an electrochemical sensor array to suppress the influence of humidity. Partial least squares (PLS) method was used to quantify the mixture composition. The experiment reveals that the sufficient accuracy was obtained. Moreover, the olfactory display, which present scents to human noses, is explained. A multi-component olfactory display enables the presentation of a variety of smells. The two types of multi-component olfactory display are described. The first one uses many solenoid valves with high speed switching. The valve ON frequency determines the concentration of the corresponding odor component. The latter one consists of miniaturized liquid pumps and a surface acoustic wave (SAW) atomizer. It enables the wearable olfactory display without smell persistence. Finally, the application of the olfactory display is demonstrated. Virtual ice cream shop with scents was made as a content of interactive art. People can enjoy harmony among vision, audition and olfaction. In conclusion, both odor sensing system and olfactory display can contribute to the field of human health care.

  18. The significance of small intestinal epithelium in gastric antral biopsies in children.

    PubMed

    Weinberg, Arthur G

    2012-01-01

    Intestinal metaplasia of the gastric antrum is common in adults with chronic gastritis and occurs in Helicobacter -associated gastritis in children. This study examined the frequency and clinical correlates of intestinal epithelium in 1690 consecutive antral biopsies obtained from children over a 2-year period in a tertiary pediatric care facility. Intestinal epithelium in gastric glands not associated with overlying villi was present in 22 (1.3%) biopsies. These came from 20 patients, 2-17 years of age, none of whom had clinical or histologic evidence of Helicobacter infection or significant chronic gastritis. Eight (40%) had an antral pancreatic rest, 8 had some other localized antral abnormality, and 4 were endoscopically normal. Four additional patients with a pancreatic rest had no intestinal epithelium. Six surgically resected rests and 2 rests found at autopsy were also reviewed. Heterotopic intestinal epithelium was present in 1 of the 2 postmortem specimens but was absent from all 6 surgically resected lesions. No intestinal epithelium was present in 67 antral biopsies with Helicobacter gastritis observed during this same period. Although the intestinal epithelium in these patients could be metaplastic, it more likely represents inadvertent sampling of the gastroduodenal junction induced by a lesion in the distal antrum or a focus of heterotopic epithelium and might best be addressed in the surgical pathology report by a comment to this effect. The distinction from metaplasia is more than semantic, because a diagnosis of intestinal metaplasia can have adverse clinical implications and should be made with caution in a child.

  19. Ex vivo culture of the intestinal epithelium: strategies and applications.

    PubMed

    Leushacke, Marc; Barker, Nick

    2014-08-01

    Limited pools of resident adult stem cells are critical effectors of epithelial renewal in the intestine throughout life. Recently, significant progress has been made regarding the isolation and in vitro propagation of fetal and adult intestinal stem cells in mammals. It is now possible to generate ever-expanding, three-dimensional epithelial structures in culture that closely parallel the in vivo epithelium of the intestine. Growing such organotypic epithelium ex vivo facilitates a detailed description of endogenous niche factors or stem-cell characteristics, as they can be monitored in real time. Accordingly, this technology has already greatly contributed to our understanding of intestinal adult stem-cell renewal and differentiation. Transplanted organoids have also been proven to readily integrate into, and effect the long-term repair of, mouse colonic epithelia in vivo, establishing the organoid culture as a promising tool for adult stem cell/gene therapy. In another exciting development, novel genome-editing techniques have been successfully employed to functionally repair disease loci in cultured intestinal stem cells from human patients with a hereditary defect. It is anticipated that this technology will be instrumental in exploiting the regenerative medicine potential of human intestinal stem cells for treating human disorders in the intestinal tract and for creating near-physiological ex vivo models of human gastrointestinal disease.

  20. Visualizing the engram: learning stabilizes odor representations in the olfactory network.

    PubMed

    Shakhawat, Amin M D; Gheidi, Ali; Hou, Qinlong; Dhillon, Sandeep K; Marrone, Diano F; Harley, Carolyn W; Yuan, Qi

    2014-11-12

    The nature of memory is a central issue in neuroscience. How does our representation of the world change with learning and experience? Here we use the transcription of Arc mRNA, which permits probing the neural representations of temporally separated events, to address this in a well characterized odor learning model. Rat pups readily associate odor with maternal care. In pups, the lateralized olfactory networks are independent, permitting separate training and within-subject control. We use multiday training to create an enduring memory of peppermint odor. Training stabilized rewarded, but not nonrewarded, odor representations in both mitral cells and associated granule cells of the olfactory bulb and in the pyramidal cells of the anterior piriform cortex. An enlarged core of stable, likely highly active neurons represent rewarded odor at both stages of the olfactory network. Odor representations in anterior piriform cortex were sparser than typical in adult rat and did not enlarge with learning. This sparser representation of odor is congruent with the maturation of lateral olfactory tract input in rat pups. Cortical representations elsewhere have been shown to be highly variable in electrophysiological experiments, suggesting brains operate normally using dynamic and network-modulated representations. The olfactory cortical representations here are consistent with the generalized associative model of sparse variable cortical representation, as normal responses to repeated odors were highly variable (∼70% of the cells change as indexed by Arc). Learning and memory modified rewarded odor ensembles to increase stability in a core representational component.

  1. Unraveling Cajal's view of the olfactory system

    PubMed Central

    Figueres-Oñate, María; Gutiérrez, Yolanda; López-Mascaraque, Laura

    2014-01-01

    The olfactory system has a highly regular organization of interconnected synaptic circuits from the periphery. It is therefore an excellent model for understanding general principles about how the brain processes information. Cajal revealed the basic cell types and their interconnections at the end of the XIX century. Since his original descriptions, the observation and analysis of the olfactory system and its components represents a major topic in neuroscience studies, providing important insights into the neural mechanisms. In this review, we will highlight the importance of Cajal contributions and his legacy to the actual knowledge of the olfactory system. PMID:25071462

  2. Immunohistochemical analysis for G protein in the olfactory organs of soft-shelled turtle, Pelodiscus sinensis

    PubMed Central

    NAKAMUTA, Shoko; YOKOSUKA, Makoto; TANIGUCHI, Kazumi; YAMAMOTO, Yoshio; NAKAMUTA, Nobuaki

    2015-01-01

    In turtles, the epithelia lining the upper and lower chambers of the nasal cavity project axons to the ventral and dorsal parts of the olfactory bulbs, respectively. In a semi-aquatic soft-shelled turtle, Pelodiscus sinensis, more than 1,000 odorant receptor genes have been found, but it is not known where they are expressed. In this study, we aimed to clarify the distribution of cells expressing these genes in the olfactory organs of soft-shelled turtles. Immunoreactions for the Gαolf, the α subunit of G protein coupled to the odorant receptors, were detected on the surface of epithelia lining both the upper and lower chambers of the nasal cavity. The receptor cells in the epithelium of both chambers possessed cilia on the tip of their dendrites, whereas microvillous, non-ciliated, receptor cells were not found. These data suggest that the odorant receptor genes are expressed by the ciliated receptor cells in the upper and lower chamber epithelia. Precise location of the vomeronasal epithelium is not known at present. PMID:26440778

  3. True navigation in migrating gulls requires intact olfactory nerves

    PubMed Central

    Wikelski, Martin; Arriero, Elena; Gagliardo, Anna; Holland, Richard A.; Huttunen, Markku J.; Juvaste, Risto; Mueller, Inge; Tertitski, Grigori; Thorup, Kasper; Wild, Martin; Alanko, Markku; Bairlein, Franz; Cherenkov, Alexander; Cameron, Alison; Flatz, Reinhard; Hannila, Juhani; Hüppop, Ommo; Kangasniemi, Markku; Kranstauber, Bart; Penttinen, Maija-Liisa; Safi, Kamran; Semashko, Vladimir; Schmid, Heidi; Wistbacka, Ralf

    2015-01-01

    During migratory journeys, birds may become displaced from their normal migratory route. Experimental evidence has shown that adult birds can correct for such displacements and return to their goal. However, the nature of the cues used by migratory birds to perform long distance navigation is still debated. In this experiment we subjected adult lesser black-backed gulls migrating from their Finnish/Russian breeding grounds (from >60°N) to Africa (to < 5°N) to sensory manipulation, to determine the sensory systems required for navigation. We translocated birds westward (1080 km) or eastward (885 km) to simulate natural navigational challenges. When translocated westwards and outside their migratory corridor birds with olfactory nerve section kept a clear directional preference (southerly) but were unable to compensate for the displacement, while intact birds and gulls with the ophthalmic branch of the trigeminal nerve sectioned oriented towards their population-specific migratory corridor. Thus, air-borne olfactory information seems to be important for migrating gulls to navigate successfully in some circumstances. PMID:26597351

  4. Molecular recognition of ketamine by a subset of olfactory G protein–coupled receptors

    PubMed Central

    Saven, Jeffery G.; Matsunami, Hiroaki; Eckenhoff, Roderic G.

    2015-01-01

    Ketamine elicits various neuropharmacological effects, including sedation, analgesia, general anesthesia, and antidepressant activity. Through an in vitro screen, we identified four mouse olfactory receptors (ORs) that responded to ketamine. In addition to their presence in the olfactory epithelium, these G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptors (GPCRs) are distributed throughout the central nervous system. To better understand the molecular basis of the interactions between ketamine and ORs, we used sequence comparison and molecular modeling to design mutations that (i) increased, reduced, or abolished ketamine responsiveness in responding receptors, and (ii) rendered non-responding receptors responsive to ketamine. We showed that olfactory sensory neurons (OSNs) that expressed distinct ORs responded to ketamine in vivo, suggesting that ORs may serve as functional targets for ketamine. The ability to both abolish and introduce responsiveness to ketamine in GPCRs enabled us to identify and confirm distinct interaction loci in the binding site, which suggested a signature ketamine-binding pocket that may guide exploration of additional receptors for this general anesthetic drug. PMID:25829447

  5. Transcriptomic profiles of the upper olfactory rosette in cultured and wild Senegalese sole (Solea senegalensis) males.

    PubMed

    Fatsini, E; Bautista, R; Manchado, M; Duncan, N J

    2016-12-01

    The aims of this study were the characterization of the upper olfactory epithelium of cultured and wild Senegalese sole mature males at histological and transcriptomic (using RNA-Seq) level. No significant differences in tissue structure, cell types and cellular distribution pattern (olfactory sensory neurons) were identified between cultured and wild specimens. Deep transcriptomic analysis showed 2387 transcripts were differentially expressed between cultured and wild groups. A detailed analysis identified the differentially expressed transcripts included some olfactory receptors (OR, TAAR and V2R-like) and transcripts related with the control of reproduction such as the brain aromatase cytochrome P450 and tachykinin-3. Also a wide set of genes related with lipid sensing, metabolism and transport were differentially expressed and these transcripts were often down-regulated in cultured fish. Furthermore, cultured males presented a higher expression of genes related with goblet cells and mucin production that modulates innate and adaptive immune responses. All these changes in gene expression could be explained by different nutritional status and diet preference. The different expression of transcripts related to olfaction, reproduction, nutrient sensing and immune system demonstrate distinct differences in functionalities between cultured and wild soles providing new clues about the sexual dysfunction in this species.

  6. Olfactory uptake of manganese requires DMT1 and is enhanced by anemia

    PubMed Central

    Thompson, Khristy; Molina, Ramon M.; Donaghey, Thomas; Schwob, James E.; Brain, Joseph D.; Wessling-Resnick, Marianne

    2008-01-01

    Manganese, an essential nutrient, can also elicit toxicity in the central nervous system (CNS). The route of exposure strongly influences the potential neurotoxicity of manganese-containing compounds. Recent studies suggest that inhaled manganese can enter the rat brain through the olfactory system, but little is known about the molecular factors involved. Divalent metal transporter-1 (DMT1) is the major transporter responsible for intestinal iron absorption and its expression is regulated by body iron status. To examine the potential role of this transporter in uptake of inhaled manganese, we studied the Belgrade rat, since these animals display significant defects in both iron and manganese metabolism due to a glycine-to-arginine substitution (G185R) in their DMT1 gene product. Absorption of intranasally instilled 54Mn was significantly reduced in Belgrade rats and was enhanced in iron-deficient rats compared to iron-sufficient controls. Immunohistochemical experiments revealed that DMT1 was localized to both the lumen microvilli and end feet of the sustentacular cells of the olfactory epithelium. Importantly, we found that DMT1 protein levels were increased in anemic rats. The apparent function of DMT1 in olfactory manganese absorption suggests that the neurotoxicity of the metal can be modified by iron status due to the iron-responsive regulation of the transporter. PMID:17116743

  7. Ductal barriers in mammary epithelium

    PubMed Central

    Owens, Mark B; Hill, Arnold DK; Hopkins, Ann M

    2013-01-01

    Tissue barriers play an integral role in the biology and pathobiology of mammary ductal epithelium. In normal breast physiology, tight and adherens junctions undergo dynamic changes in permeability in response to hormonal and other stimuli, while several of their proteins are directly involved in mammary tumorigenesis. This review describes first the structure of mammary ductal epithelial barriers and their role in normal mammary development, examining the cyclical changes in response to puberty, pregnancy, lactation and involution. It then examines the role of adherens and tight junctions and the participation of their constituent proteins in mammary tumorigenic functions such as migration, invasion and metastasis. Finally, it discusses the potential of these adhesion proteins as both prognostic biomarkers and potential therapeutic targets in breast cancer. PMID:24665412

  8. Pharmacology of mammalian olfactory receptors.

    PubMed

    Smith, Richard S; Peterlin, Zita; Araneda, Ricardo C

    2013-01-01

    Mammalian species have evolved a large and diverse number of odorant receptors (ORs). These proteins comprise the largest family of G-protein-coupled receptors (GPCRs) known, amounting to ~1,000-different receptors in the rodent. From the perspective of olfactory coding, the availability of such a vast number of chemosensory receptors poses several fascinating questions; in addition, such a large repertoire provides an attractive biological model to study ligand-receptor interactions. The limited functional expression of these receptors in heterologous systems, however, has greatly hampered attempts to deorphanize them. We have employed a successful approach that combines electrophysiological and imaging techniques to analyze the response profiles of single sensory neurons. Our approach has enabled us to characterize the "odor space" of a population of native aldehyde receptors and the molecular range of a genetically engineered receptor, OR-I7.

  9. Modeling Olfactory Bulb Evolution through Primate Phylogeny

    PubMed Central

    Heritage, Steven

    2014-01-01

    Adaptive characterizations of primates have usually included a reduction in olfactory sensitivity. However, this inference of derivation and directionality assumes an ancestral state of olfaction, usually by comparison to a group of extant non-primate mammals. Thus, the accuracy of the inference depends on the assumed ancestral state. Here I present a phylogenetic model of continuous trait evolution that reconstructs olfactory bulb volumes for ancestral nodes of primates and mammal outgroups. Parent-daughter comparisons suggest that, relative to the ancestral euarchontan, the crown-primate node is plesiomorphic and that derived reduction in olfactory sensitivity is an attribute of the haplorhine lineage. The model also suggests a derived increase in olfactory sensitivity at the strepsirrhine node. This oppositional diversification of the strepsirrhine and haplorhine lineages from an intermediate and non-derived ancestor is inconsistent with a characterization of graded reduction through primate evolution. PMID:25426851

  10. Satratoxin G from the black mold Stachybotrys chartarum evokes olfactory sensory neuron loss and inflammation in the murine nose and brain.

    PubMed

    Islam, Zahidul; Harkema, Jack R; Pestka, James J

    2006-07-01

    Satratoxin G (SG) is a macrocyclic trichothecene mycotoxin produced by Stachybotrys chartarum, the "black mold" suggested to contribute etiologically to illnesses associated with water-damaged buildings. Using an intranasal instillation model in mice, we found that acute SG exposure specifically induced apoptosis of olfactory sensory neurons (OSNs) in the olfactory epithelium. Dose-response analysis revealed that the no-effect and lowest-effect levels at 24 hr postinstillation (PI) were 5 and 25 microg/kg body weight (bw) SG, respectively, with severity increasing with dose. Apoptosis of OSNs was identified using immunohistochemistry for caspase-3 expression, electron microscopy for ultrastructural cellular morphology, and real-time polymerase chain reaction for elevated expression of the proapoptotic genes Fas, FasL, p75NGFR, p53, Bax, caspase-3, and CAD. Time-course studies with a single instillation of SG (500 microg/kg bw) indicated that maximum atrophy of the olfactory epithelium occurred at 3 days PI. Exposure to lower doses (100 microg/kg bw) for 5 consecutive days resulted in similar atrophy and apoptosis, suggesting that in the short term, these effects are cumulative. SG also induced an acute, neutrophilic rhinitis as early as 24 hr PI. Elevated mRNA expression for the proinflammatory cytokines tumor necrosis factor-alpha, interleukin-6 (IL-6) , and IL-1 and the chemokine macrophage-inflammatory protein-2 (MIP-2) were detected at 24 hr PI in both the ethmoid turbinates of the nasal airways and the adjacent olfactory bulb of the brain. Marked atrophy of the olfactory nerve and glomerular layers of the olfactory bulb was also detectable by 7 days PI along with mild neutrophilic encephalitis. These findings suggest that neurotoxicity and inflammation within the nose and brain are potential adverse health effects of exposure to satratoxins and Stachybotrys in the indoor air of water-damaged buildings.

  11. Dimorphic olfactory lobes in the arthropoda.

    PubMed

    Strausfeld, Nicholas; Reisenman, Carolina E

    2009-07-01

    Specialized olfactory lobe glomeruli relating to sexual or caste differences have been observed in at least five orders of insects, suggesting an early appearance of this trait in insect evolution. Dimorphism is not limited to nocturnal species, but occurs even in insects that are known to use vision for courtship. Other than a single description, there is no evidence for similar structures occurring in the Crustacea, suggesting that the evolution of dimorphic olfactory systems may typify terrestrial arthropods.

  12. Cladistic Analysis of Olfactory and Vomeronasal Systems

    PubMed Central

    Ubeda-Bañon, Isabel; Pro-Sistiaga, Palma; Mohedano-Moriano, Alicia; Saiz-Sanchez, Daniel; de la Rosa-Prieto, Carlos; Gutierrez-Castellanos, Nicolás; Lanuza, Enrique; Martinez-Garcia, Fernando; Martinez-Marcos, Alino

    2010-01-01

    Most tetrapods possess two nasal organs for detecting chemicals in their environment, which are the sensory detectors of the olfactory and vomeronasal systems. The seventies’ view that the olfactory system was only devoted to sense volatiles, whereas the vomeronasal system was exclusively specialized for pheromone detection was challenged by accumulating data showing deep anatomical and functional interrelationships between both systems. In addition, the assumption that the vomeronasal system appeared as an adaptation to terrestrial life is being questioned as well. The aim of the present work is to use a comparative strategy to gain insight in our understanding of the evolution of chemical “cortex.” We have analyzed the organization of the olfactory and vomeronasal cortices of reptiles, marsupials, and placental mammals and we have compared our findings with data from other taxa in order to better understand the evolutionary history of the nasal sensory systems in vertebrates. The olfactory and vomeronsasal cortices have been re-investigated in garter snakes (Thamnophis sirtalis), short-tailed opossums (Monodelphis domestica), and rats (Rattus norvegicus) by tracing the efferents of the main and accessory olfactory bulbs using injections of neuroanatomical anterograde tracers (dextran-amines). In snakes, the medial olfactory tract is quite evident, whereas the main vomeronasal-recipient structure, the nucleus sphaericus is a folded cortical-like structure, located at the caudal edge of the amygdala. In marsupials, which are acallosal mammals, the rhinal fissure is relatively dorsal and the olfactory and vomeronasal cortices relatively expanded. Placental mammals, like marsupials, show partially overlapping olfactory and vomeronasal projections in the rostral basal telencephalon. These data raise the interesting question of how the telencephalon has been re-organized in different groups according to the biological relevance of chemical senses. PMID:21290004

  13. Cladistic analysis of olfactory and vomeronasal systems.

    PubMed

    Ubeda-Bañon, Isabel; Pro-Sistiaga, Palma; Mohedano-Moriano, Alicia; Saiz-Sanchez, Daniel; de la Rosa-Prieto, Carlos; Gutierrez-Castellanos, Nicolás; Lanuza, Enrique; Martinez-Garcia, Fernando; Martinez-Marcos, Alino

    2011-01-01

    Most tetrapods possess two nasal organs for detecting chemicals in their environment, which are the sensory detectors of the olfactory and vomeronasal systems. The seventies' view that the olfactory system was only devoted to sense volatiles, whereas the vomeronasal system was exclusively specialized for pheromone detection was challenged by accumulating data showing deep anatomical and functional interrelationships between both systems. In addition, the assumption that the vomeronasal system appeared as an adaptation to terrestrial life is being questioned as well. The aim of the present work is to use a comparative strategy to gain insight in our understanding of the evolution of chemical "cortex." We have analyzed the organization of the olfactory and vomeronasal cortices of reptiles, marsupials, and placental mammals and we have compared our findings with data from other taxa in order to better understand the evolutionary history of the nasal sensory systems in vertebrates. The olfactory and vomeronsasal cortices have been re-investigated in garter snakes (Thamnophis sirtalis), short-tailed opossums (Monodelphis domestica), and rats (Rattus norvegicus) by tracing the efferents of the main and accessory olfactory bulbs using injections of neuroanatomical anterograde tracers (dextran-amines). In snakes, the medial olfactory tract is quite evident, whereas the main vomeronasal-recipient structure, the nucleus sphaericus is a folded cortical-like structure, located at the caudal edge of the amygdala. In marsupials, which are acallosal mammals, the rhinal fissure is relatively dorsal and the olfactory and vomeronasal cortices relatively expanded. Placental mammals, like marsupials, show partially overlapping olfactory and vomeronasal projections in the rostral basal telencephalon. These data raise the interesting question of how the telencephalon has been re-organized in different groups according to the biological relevance of chemical senses.

  14. Specific mesenchymal/epithelial induction of olfactory receptor, vomeronasal, and gonadotropin-releasing hormone (GnRH) neurons

    PubMed Central

    Rawson, N.E; Lischka, F. W.; Yee, K.K.; Peters, A.Z.; Tucker, E.S.; Meechan, D.W.; Zirlinger, M.; Maynard, T.M.; Burd, G.B.; Dulac, C.; Pevny, L.; LaMantia, A-S.

    2013-01-01

    We asked whether specific mesenchymal/epithelial (M/E) induction generates olfactory receptor neurons (ORNs), vomeronasal neurons (VRNs) and gonadotropin releasing hormone (GnRH) neurons—the major neuron classes associated with the olfactory epithelium (OE). To assess specificity of M/E-mediated neurogenesis, we compared the influence of frontonasal mesenchyme on frontonasal epithelium, which becomes the OE, with that of the forelimb bud. Despite differences in position, morphogenetic and cytogenic capacity, both mesenchymal tissues support neurogenesis, expression of several signaling molecules and neurogenic transcription factors in the frontonasal epithelium. Only frontonasal mesenchyme, however, supports OE-specific patterning and activity of a subset of signals and factors associated with OE differentiation. Moreover, only appropriate pairing of frontonasal epithelial and mesenchymal partners yields ORNs, VRNs, and GnRH neurons. Accordingly, the position and molecular identity of specialized frontonasal epithelia and mesenchyme early in gestation and subsequent inductive interactions, specifies the genesis and differentiation of peripheral chemosensory and neuroendocrine neurons. PMID:20503368

  15. A new dopaminergic nigro-olfactory projection.

    PubMed

    Höglinger, Günter U; Alvarez-Fischer, Daniel; Arias-Carrión, Oscar; Djufri, Miriam; Windolph, Andrea; Keber, Ursula; Borta, Andreas; Ries, Vincent; Schwarting, Rainer K W; Scheller, Dieter; Oertel, Wolfgang H

    2015-09-01

    Parkinson disease (PD) is a neurodegenerative disorder characterized by massive loss of midbrain dopaminergic neurons. Whereas onset of motor impairments reflects a rather advanced stage of the disorder, hyposmia often marks the beginning of the disease. Little is known about the role of the nigro-striatal system in olfaction under physiological conditions and the anatomical basis of hyposmia in PD. Yet, the early occurrence of olfactory dysfunction implies that pathogens such as environmental toxins could incite the disease via the olfactory system. In the present study, we demonstrate a dopaminergic innervation from neurons in the substantia nigra to the olfactory bulb by axonal tracing studies. Injection of two dopaminergic neurotoxins-1-methyl-4-phenylpyridinium and 6-hydroxydopamine-into the olfactory bulb induced a decrease in the number of dopaminergic neurons in the substantia nigra. In turn, ablation of the nigral projection led to impaired olfactory perception. Hyposmia following dopaminergic deafferentation was reversed by treatment with the D1/D2/D3 dopamine receptor agonist rotigotine. Hence, we demonstrate for the first time the existence of a direct dopaminergic projection into the olfactory bulb and identify its origin in the substantia nigra in rats. These observations may provide a neuroanatomical basis for invasion of environmental toxins into the basal ganglia and for hyposmia as frequent symptom in PD.

  16. Spatial Distribution of Gyrodactylus salmonis (Monogenea) on the Body of Captive Fingerling Oncorhynchus mykiss, Including Attachment Within the Olfactory Chamber.

    PubMed

    Lari, Ebrahim; Cone, David K; Goater, Cameron P; Pyle, Greg G

    2016-04-01

    Gyrodactylus salmonis is a common ectoparasite on the fins and body of North American salmonids in fresh water. In this study, the spatial distribution of G. salmonis on 60 captive hatchery-reared rainbow trout, Oncorhynchus mykiss , is reported. The highest parasite densities occurred on 5 × 5-mm(2) sections of the dorsal fin followed by the trunk, other fins, and the olfactory chamber, with the lowest densities on the head. The finding of infections within the olfactory chamber of 93% of the fish was unexpected. One possibility is that such infections represented spillover from high-density infrapopulations that occur on the skin and fins. However, this possibility is unlikely, because worm densities at various sites along the body surface of infected fish did not correlate with densities within the olfactory chamber. The parasite conceivably enters the chamber either via water incurrent or by crawling in from the head and subsequently remaining at this site to feed and reproduce. Results from scanning electron microscopy are consistent with physical modification to the olfactory epithelium associated with the attachment/reattachment of the opisthaptor and epithelial grazing.

  17. Mexico City air pollution adversely affects olfactory function and intranasal trigeminal sensitivity.

    PubMed

    Guarneros, Marco; Hummel, Thomas; Martínez-Gómez, Margaríta; Hudson, Robyn

    2009-11-01

    Surprisingly little is known about the effects of big-city air pollution on olfactory function and even less about its effects on the intranasal trigeminal system, which elicits sensations like burning, stinging, pungent, or fresh and contributes to the overall chemosensory experience. Using the Sniffin' Sticks olfactory test battery and an established test for intranasal trigeminal perception, we compared the olfactory performance and trigeminal sensitivity of residents of Mexico City, a region with high air pollution, with the performance of a control population from the Mexican state of Tlaxcala, a geographically comparable but less polluted region. We compared the ability of 30 young adults from each location to detect a rose-like odor (2-phenyl ethanol), to discriminate between different odorants, and to identify several other common odorants. The control subjects from Tlaxcala detected 2-phenyl ethanol at significantly lower concentrations than the Mexico City subjects, they could discriminate between odorants significantly better, and they performed significantly better in the test of trigeminal sensitivity. We conclude that Mexico City air pollution impairs olfactory function and intranasal trigeminal sensitivity, even in otherwise healthy young adults.

  18. Activin Potentiates Proliferation in Mature Avian Auditory Sensory Epithelium

    PubMed Central

    McCullar, Jennifer S.; Ty, Sidya; Campbell, Sean; Oesterle, Elizabeth C.

    2010-01-01

    Humans and other mammals are highly susceptible to permanent hearing and balance deficits due to an inability to regenerate sensory hair cells lost to inner ear trauma. In contrast, nonmammalian vertebrates, such as birds, robustly regenerate replacement hair cells and restore hearing and balance functions to near-normal levels. There is considerable interest in understanding the cellular mechanisms responsible for this difference in regenerative capacity. Here we report on involvement of the TGFβ superfamily type II activin receptors, Acvr2a and Acvr2b, in regulating proliferation in mature avian auditory sensory epithelium. Cultured, posthatch avian auditory sensory epithelium treated with Acvr2a and Acvr2b inhibitors shows decreased proliferation of support cells, the cell type that gives rise to new hair cells. Conversely, addition of activin A, an Acvr2a/b ligand, potentiates support cell proliferation. Neither treatment (inhibitor or ligand) affected hair cell survival, suggesting a specific effect of Acvr2a/b signaling on support cell mitogenicity. Using immunocytochemistry, Acvr2a, Acvr2b, and downstream Smad effector proteins were differentially localized in avian and mammalian auditory sensory epithelia. Collectively, these data suggest that signaling through Acvr2a/b promotes support cell proliferation in mature avian auditory sensory epithelium and that this signaling pathway may be incomplete, or actively blocked, in the adult mammalian ear. PMID:20071511

  19. Olfactory and erectile dysfunction association in smoking and non-smoking men.

    PubMed

    Özmen, Süay; Dülger, Seyhan; Çoban, Soner; Özmen, Ömer Afşın; Güzelsoy, Muhammed; Dikiş, Özlem Şengören; Akdeniz, Önder

    2016-06-01

    The studies evaluating the effect of smoking on olfaction reveals opposite results. In vitro and animal studies and epidemiological evidence from volunteers and patients, demonstrated the association between olfaction and erectile functions. In smoking man the reduction of olfactory acuity could adversely affect sexuality. The aim of the present study was to investigate the relationship between erectile dysfunction (ED) and olfactory dysfunction (OD) by comparing a group of healthy adult men with a group of smoking adult men. This prospective study involved 62 volunteers, who were recruited and divided into two groups; one consisted of 35 smoking adult men, and the other included 27 healthy non-smoking men. All participants in both groups were examined in detail for any condition with the potential to cause OD. They all had a normal genitourinary system suffered from no circulatory diseases, diabetes mellitus, hypertension, coronary artery disease nor hyperlipidemia; they had no history of medication affecting genitourinary system. Butanol threshold test and sniffin' stick® (Burghart, Wedel; Germany) screening test was used to asses olfactory functions in both groups. Participants' sexual desire was assessed using an International Index of Erectile Function (IIEF-5) scale. The means of sniffin' sticks scores, butanol threshold scores and IIEF-5 scores were statistically higher in non-smoking group. Butanol threshold scores and sniffin' sticks scores are correlated statistically with IIEF-5 in non-smoking and smoking groups. This study found an association between olfaction and erectile function in smoking and non-smoking men. As far as we know this study is the third published study to show the relationship olfactory and erectile function. In the future studies electrophysiological olfactory methods could be used to confirm in large cohorts the results obtained by the psychophysical approach.

  20. The olfactory pathway of decapod crustaceans--an invertebrate model for life-long neurogenesis.

    PubMed

    Schmidt, Manfred

    2007-05-01

    The first part of this review includes a short description of the cellular and morphological organization of the olfactory pathway of decapod crustaceans, followed by an overview of adult neurogenesis in this pathway focusing on the olfactory lobe (OL), the first synaptic relay in the brain. Adult neurogenesis in the central olfactory pathway has the following characteristics. 1) It is present in all the diverse species of decapod crustaceans so far studied. 2) In all these species, projection neurons (PNs), which have multiglomerular dendritic arborizations, are generated. 3) Neurons are generated by one round of symmetrical cell divisions of a small population of immediate precursor cells that are located in small proliferation zones at the inner margin of the respective soma clusters. 4) The immediate precursor cells in each soma cluster appear to be generated by repeated cell divisions of one or few neuronal stem cells that are located outside of the proliferation zone. 5) These neuronal stem cells are enclosed in a highly structured clump of small glial-like cells, which likely establishes a specific microenvironment and thus can be regarded as a stem cell niche. 6) Diverse internal and external factors, such as presence of olfactory afferents, age, season of the year, and living under constant and deprived conditions modulate the generation and/or survival of new neurons. In the second part of this review, I address the question why in decapod crustaceans adult neurogenesis persists in the visual and olfactory pathways of the brain but is lacking in all other mechanosensory-chemosensory pathways. Due to the indeterminate growth of most adult decapod crustaceans, new sensory neurons of all modalities (olfaction and chemo-, mechano-, and photoreception) are continuously added during adulthood and provide an ever-increasing sensory input to all primary sensory neuropils of the central nervous system. From these facts, I conclude that adult neurogenesis in the

  1. Lectin binding to olfactory system in a shark, Scyliorhinus canicula.

    PubMed

    Franceschini, V; Ciani, F

    1993-01-01

    Lectin histochemical studies were performed on the olfactory system of Scyliorhinus canicula to identify specific glycoconjugates on the cell surface of primary olfactory neurons. The olfactory receptor cells, the olfactory nerve fibers and their terminals in the bulbs were labelled with SBA, BSA-I and BSA-I-B4. The lectin staining patterns indicate that the membranes of small-spotted catshark olfactory neurons had glycoproteins with alpha-galactose residues. This carbohydrate moiety could be related to modulation of the cell-cell interactions in the olfactory system.

  2. Olfactory Fear Conditioning Induces Field Potential Potentiation in Rat Olfactory Cortex and Amygdala

    ERIC Educational Resources Information Center

    Messaoudi, Belkacem; Granjon, Lionel; Mouly, Anne-Marie; Sevelinges, Yannick; Gervais, Remi

    2004-01-01

    The widely used Pavlovian fear-conditioning paradigms used for studying the neurobiology of learning and memory have mainly used auditory cues as conditioned stimuli (CS). The present work assessed the neural network involved in olfactory fear conditioning, using olfactory bulb stimulation-induced field potential signal (EFP) as a marker of…

  3. Olfactory Receptors in Non-Chemosensory Organs: The Nervous System in Health and Disease

    PubMed Central

    Ferrer, Isidro; Garcia-Esparcia, Paula; Carmona, Margarita; Carro, Eva; Aronica, Eleonora; Kovacs, Gabor G.; Grison, Alice; Gustincich, Stefano

    2016-01-01

    Olfactory receptors (ORs) and down-stream functional signaling molecules adenylyl cyclase 3 (AC3), olfactory G protein α subunit (Gαolf), OR transporters receptor transporter proteins 1 and 2 (RTP1 and RTP2), receptor expression enhancing protein 1 (REEP1), and UDP-glucuronosyltransferases (UGTs) are expressed in neurons of the human and murine central nervous system (CNS). In vitro studies have shown that these receptors react to external stimuli and therefore are equipped to be functional. However, ORs are not directly related to the detection of odors. Several molecules delivered from the blood, cerebrospinal fluid, neighboring local neurons and glial cells, distant cells through the extracellular space, and the cells’ own self-regulating internal homeostasis can be postulated as possible ligands. Moreover, a single neuron outside the olfactory epithelium expresses more than one receptor, and the mechanism of transcriptional regulation may be different in olfactory epithelia and brain neurons. OR gene expression is altered in several neurodegenerative diseases including Parkinson’s disease (PD), Alzheimer’s disease (AD), progressive supranuclear palsy (PSP) and sporadic Creutzfeldt-Jakob disease (sCJD) subtypes MM1 and VV2 with disease-, region- and subtype-specific patterns. Altered gene expression is also observed in the prefrontal cortex in schizophrenia with a major but not total influence of chlorpromazine treatment. Preliminary parallel observations have also shown the presence of taste receptors (TASRs), mainly of the bitter taste family, in the mammalian brain, whose function is not related to taste. TASRs in brain are also abnormally regulated in neurodegenerative diseases. These seminal observations point to the need for further studies on ORs and TASRs chemoreceptors in the mammalian brain. PMID:27458372

  4. Infradian biorhythms of mitotic activity esophageal epithelium in male Wistar rats.

    PubMed

    Diatroptov, M E; Makarova, O V

    2015-01-01

    Infradian rhythms of esophageal epithelium mitotic activity were studied in male Wistar rats of two age groups: 35-45 days (prepubertal) and 3-4 months (adults). Studies of the time course of esophageal epithelium mitotic indexes in adult males showed 4- and 12-day biorhythms, while prepubertal rats exhibited only 4-day infradian biorhythms of this parameter. Studies of the mitotic activity over long periods (3 years) showed 4.058- and 12.175-day periodicity of infradian biorhythms for this parameter, presumably due to external exposures synchronizing the biorhythms. Studies of the mean daily values of the Bz component of interplanetary magnetic field during the period of our research (2012-2013) showed rhythmicities analogous to changes in the mitotic activity of the epithelium. The minimum mitotic indexes were detected on the days of the most pronounced negative values of the interplanetary magnetic field Bz component.

  5. Olfactory dysfunction in acute rhinosinusitis: intranasal sodium hyaluronate as adjuvant treatment.

    PubMed

    Ciofalo, Andrea; de Vincentiis, Marco; Zambetti, Giampietro; Altissimi, Giancarlo; Fusconi, Massimo; Greco, Antonio; Ottaviano, Giancarlo; Magliulo, Giuseppe

    2017-02-01

    Acute rhinosinusitis (ARS) is defined as an inflammation of the mucosa of the nose and paranasal sinuses and affects 1-5 % of general population in Europe. Sinonasal diseases represent the main cause of smell alterations in adult patients and lead to mucosal congestion, increased quantity and density of secretions and altered mucociliary transport. For this reason the odorous molecules contained in the inspired air, cannot interact with the olfactory epithelium. Medical therapy of ARS has to reduce the severity and duration of symptoms and prevent complications. Recent studies have shown that Sodium hyaluronate modulate inflammation and has a reparative effect on the nasal mucosa. 48 patients affected by acute rhinosinusitis proven by CT scan, were enrolled. They were submitted to nasal endoscopy, olfactometric and mucociliary transport evaluation (MCTt), Visual Analogue Scale Questionnaire (VAS) at T0, after 14-18 days (T1) and after 30-35 days (T2). The patients were randomized into two treatment groups, A and B, and were treated for 30 days; each group was composed of 24 subjects. All patients received Levofloxacin (500 mg for 10 days) and Prednisone (50 mg for 8 days, 25 mg for 4 days and 12, 5 mg for 4 days). Moreover, Group A received twice a day for 30 days high molecular weight Sodium Hyaluronate (3 %) plus saline solution (3 mL sodium chloride-NaCl-0.9 %) using a nebulizer ampoule for nasal douche. Group B received twice a day for 30 days saline solution (6 mL sodium chloride-NaCl-0.9 %) using a nebulizer ampoule for nasal douche. At T1 Group A shown lower values in MCTt and threshold score was significantly higher than in Group B. VAS showed statistically significant differences between the two groups, in particular for smell, nasal obstruction and for nasal discharge. At T2 Group A MCTt was significantly lower than in Group B; odour threshold improved in both groups but in Group A was still significantly higher than in Group B. No

  6. Involvement of hormones in olfactory imprinting and homing in chum salmon

    PubMed Central

    Ueda, Hiroshi; Nakamura, Shingo; Nakamura, Taro; Inada, Kaoru; Okubo, Takashi; Furukawa, Naohiro; Murakami, Reiichi; Tsuchida, Shigeo; Zohar, Yonathan; Konno, Kotaro; Watanabe, Masahiko

    2016-01-01

    The olfactory hypothesis for salmon imprinting and homing to their natal stream is well known, but the endocrine hormonal control mechanisms of olfactory memory formation in juveniles and retrieval in adults remain unclear. In brains of hatchery-reared underyearling juvenile chum salmon (Oncorhynchus keta), thyrotropin-releasing hormone gene expression increased immediately after release from a hatchery into the natal stream, and the expression of the essential NR1 subunit of the N-methyl-D-aspartate receptor increased during downstream migration. Gene expression of salmon gonadotropin-releasing hormone (sGnRH) and NR1 increased in the adult chum salmon brain during homing from the Bering Sea to the natal hatchery. Thyroid hormone treatment in juveniles enhanced NR1 gene activation, and GnRHa treatment in adults improved stream odour discrimination. Olfactory memory formation during juvenile downstream migration and retrieval during adult homing migration of chum salmon might be controlled by endocrine hormones and could be clarified using NR1 as a molecular marker. PMID:26879952

  7. Involvement of hormones in olfactory imprinting and homing in chum salmon.

    PubMed

    Ueda, Hiroshi; Nakamura, Shingo; Nakamura, Taro; Inada, Kaoru; Okubo, Takashi; Furukawa, Naohiro; Murakami, Reiichi; Tsuchida, Shigeo; Zohar, Yonathan; Konno, Kotaro; Watanabe, Masahiko

    2016-02-16

    The olfactory hypothesis for salmon imprinting and homing to their natal stream is well known, but the endocrine hormonal control mechanisms of olfactory memory formation in juveniles and retrieval in adults remain unclear. In brains of hatchery-reared underyearling juvenile chum salmon (Oncorhynchus keta), thyrotropin-releasing hormone gene expression increased immediately after release from a hatchery into the natal stream, and the expression of the essential NR1 subunit of the N-methyl-D-aspartate receptor increased during downstream migration. Gene expression of salmon gonadotropin-releasing hormone (sGnRH) and NR1 increased in the adult chum salmon brain during homing from the Bering Sea to the natal hatchery. Thyroid hormone treatment in juveniles enhanced NR1 gene activation, and GnRHa treatment in adults improved stream odour discrimination. Olfactory memory formation during juvenile downstream migration and retrieval during adult homing migration of chum salmon might be controlled by endocrine hormones and could be clarified using NR1 as a molecular marker.

  8. Stages and duration of the cycle of the seminiferous epithelium in oncilla (Leopardus tigrinus, Schreber, 1775).

    PubMed

    Balarini, Maytê Koch; de Paula, Tarcízio Antônio Rego; da Matta, S L Pinto; Peixoto, J Vogas; Guião-Leite, F Lima; Rossi Júnior, J L; Czermak Junior, A C; Walker, N J

    2012-03-15

    Six adult Leopardus tigrinus (oncilla) were studied to characterize stages of the seminiferous epithelium cycle and its relative frequency and duration, as well as morphometric parameters of the testes. Testicular fragments were obtained (incisional biopsy), embedded (glycol methacrylate), and histologic sections examined with light microscopy. The cycle of the seminiferous epithelium was categorized into eight stages (based on the tubular morphology method). The duration of one seminiferous epithelium cycle was 9.19 d, and approximately 41.37 d were required for development of sperm from spermatogonia. On average, diameter of the seminiferous tubules was 228.29 μm, epithelium height was 78.86 μm, and there were 16.99 m of testicular tubules per gram of testis. Body weight averaged 2.589 kg, of which 0.06 and 0.04% were attributed to the testis and seminiferous tubules, respectively. In conclusion, there were eight distinct stages in the seminiferous epithelium, the length of the seminiferous epithelium cycle was close to that in domestic cats and cougars, and testicular and somatic indexes were similar to those of other carnivores of similar size.

  9. Mechanisms of permanent loss of olfactory receptor neurons induced by the herbicide 2,6-dichlorobenzonitrile: Effects on stem cells and noninvolvement of acute induction of the inflammatory cytokine IL-6

    SciTech Connect

    Xie, Fang; Fang, Cheng; Schnittke, Nikolai; Schwob, James E.; Ding, Xinxin

    2013-11-01

    We explored the mechanisms underlying the differential effects of two olfactory toxicants, the herbicide 2,6-dichlorobenzonitrile (DCBN) and the anti-thyroid drug methimazole (MMZ), on olfactory receptor neuron (ORN) regeneration in mouse olfactory epithelium (OE). DCBN, but not MMZ, induced inflammation-like pathological changes in OE, and DCBN increased interleukin IL-6 levels in nasal-wash fluid to much greater magnitude and duration than did MMZ. At 24 h after DCBN injection, the population of horizontal basal cells (HBCs; reserve, normally quiescent OE stem cells) lining the DMM became severely depleted as some of them detached from the basal lamina, and sloughed into the nasal cavity along with the globose basal cells (GBCs; heterogeneous population of stem and progenitor cells), neurons, and sustentacular cells of the neuroepithelium. In contrast, the layer of HBCs remained intact in MMZ-treated mice, as only the mature elements of the neuroepithelium were shed. Despite the respiratory metaplasia accompanying the greater severity of the DCBN lesion, residual HBCs that survived intoxication were activated by the injury and contributed to the metaplastic respiratory epithelium, as shown by tracing their descendants in a K5CreEr{sup T2}::fl(stop)TdTomato strain of mice in which recombination causes HBCs to express TdTomato in advance of the lesion. But, contrary to published observations with MMZ, the HBCs failed to form ORNs. A role for IL-6 in suppressing ORN regeneration in DCBN-treated mice was rejected by the failure of the anti-inflammatory drug dexamethasone to prevent the subsequent respiratory metaplasia in the DMM, suggesting that other factors lead to HBC neuro-incompetence. - Highlights: • The herbicide dichlobenil (DCBN) can damage olfactory epithelium stem cells. • Another olfactory toxicant, methimazole, leaves the olfactory stem cells intact. • DCBN, but not methimazole, induces a prolonged increase in nasal IL-6 levels. • Dexamethasone

  10. Denervation of the primary olfactory pathway in mice. V. Long-term effect of intranasal ZnSO4 irrigation on behavior, biochemistry and morphology.

    PubMed

    Harding, J W; Getchell, T V; Margolis, F L

    1978-01-27

    Intranasal irrigation of mice with 0.17 M ZnSO4 solution results in the immediate and total loss of the ability to find a buried food pellet. This anosmia persists for 6 weeks in at least 80% of the treated mice and for 4 months in half of the animals. This marked behavioral effect is matched by a long-term reduction of the levels of carnosine synthesis and transport in the primary olfactory pathway. These biochemical parameters are virtually undetectable at two weeks after treatment and even at one year after treatment do not exceed 5-10% of average control values. Light microscopic observations of tissues of the primary olfactory pathway at various times after treatment are consistent with these observations and indicate a substantial destruction of the olfactory epithelium with subsequent atrophy of the olfactory bulb. At very long intervals after treatment, some receptor regeneration is apparent with accompanying reinnervation of the olfactory bulb. Estimates from microscopy and biochemistry suggest that much less than 10% of the normal complement of functioning receptor cells is adequate to give apparently normal food-finding behavior.

  11. The junctional epithelium originates from the odontogenic epithelium of an erupted tooth.

    PubMed

    Yajima-Himuro, Sara; Oshima, Masamitsu; Yamamoto, Gou; Ogawa, Miho; Furuya, Madoka; Tanaka, Junichi; Nishii, Kousuke; Mishima, Kenji; Tachikawa, Tetsuhiko; Tsuji, Takashi; Yamamoto, Matsuo

    2014-05-02

    The junctional epithelium (JE) is an epithelial component that is directly attached to the tooth surface and has a protective function against periodontal diseases. In this study, we determined the origin of the JE using a bioengineered tooth technique. We transplanted the bioengineered tooth germ into the alveolar bone with an epithelial component that expressed green fluorescence protein. The reduced enamel epithelium from the bioengineered tooth fused with the oral epithelium, and the JE was apparently formed around the bioengineered tooth 50 days after transplantation. Importantly, the JE exhibited green fluorescence for at least 140 days after transplantation, suggesting that the JE was not replaced by oral epithelium. Therefore, our results demonstrated that the origin of the JE was the odontogenic epithelium, and odontogenic epithelium-derived JE was maintained for a relatively long period.

  12. An Olfactory Indicator for Acid-Base Titrations.

    ERIC Educational Resources Information Center

    Flair, Mark N.; Setzer, William N.

    1990-01-01

    The use of an olfactory acid-base indicator in titrations for visually impaired students is discussed. Potential olfactory indicators include eugenol, thymol, vanillin, and thiophenol. Titrations performed with each indicator with eugenol proved to be successful. (KR)

  13. Distinct molecular underpinnings of Drosophila olfactory trace conditioning.

    PubMed

    Shuai, Yichun; Hu, Ying; Qin, Hongtao; Campbell, Robert A A; Zhong, Yi

    2011-12-13

    Trace conditioning is valued as a simple experimental model to assess how the brain associates events that are discrete in time. Here, we adapted an olfactory trace conditioning procedure in Drosophila melanogaster by training fruit flies to avoid an odor that is followed by foot shock many seconds later. The molecular underpinnings of the learning are distinct from the well-characterized simultaneous conditioning, where odor and punishment temporally overlap. First, Rutabaga adenylyl cyclase (Rut-AC), a putative molecular coincidence detector vital for simultaneous conditioning, is dispensable in trace conditioning. Second, dominant-negative Rac expression, thought to sustain early labile memory, significantly enhances learning of trace conditioning, but leaves simultaneous conditioning unaffected. We further show that targeting Rac inhibition to the mushroom body (MB) but not the antennal lobe (AL) suffices to achieve the enhancement effect. Moreover, the absence of trace conditioning learning in D1 dopamine receptor mutants is rescued by restoration of expression specifically in the adult MB. These results suggest the MB as a crucial neuroanatomical locus for trace conditioning, which may harbor a Rac activity-sensitive olfactory "sensory buffer" that later converges with the punishment signal carried by dopamine signaling. The distinct molecular signature of trace conditioning revealed here shall contribute to the understanding of how the brain overcomes a temporal gap in potentially related events.

  14. Changes of the lingual epithelium in Ambystoma mexicanum.

    PubMed

    Wistuba, J; Clemen, G

    1998-12-01

    Changes in the lingual epithelium during ontogenesis and after induced metamorphosis in Ambystoma mexicanum are described as observed by light microscopy and scanning electron microscopy. The epithelium of the tongue is always multilayered in the larva as well as in the adult. It consists of a stratum germinativum with little differentiated basal cells and a stratum superficiale (superficial layer) with specialized superficial cells and goblet cells. Usually, there are more than two layers because of a stratum intermedium consisting of replacement cells. The apical cell membrane of the superficial cells is perforated by fine pores. Its most typical feature are microridges. Maturing superficial cells possess microvilli. Goblet cells occur in early larvae primarily in the centre of the tongue. They spread throughout the dorsal face of the tongue as their numbers increase during ontogenesis. The small apices of the goblet cells are intercalated in the wedges between the superficial cells. Leydig cells are not found on the larval tongue but on that of adults. Due to metamorphosis, the epithelium of the tongue changes. It is furrowed in its anterior part. The furrows house the openings of the lingual glands. The surface is further modulated by ridges which are densely coated by microvilli and which bear the taste buds. The villi of the tongue which lack extrusion pores show cilia and microvilli but lack microridges. The Leydig cells disappear during metamorphosis. In addition to the two types of goblet cells found in different regions of the glandular tubules, goblet cells occur in the caudal part. They secrete directly into the cavity of the mouth. The posterior part is characterised by a dense coat of cilia.

  15. Olfactory phenotypic expression unveils human aging

    PubMed Central

    Mazzatenta, Andrea; Cellerino, Alessandro; Origlia, Nicola; Barloscio, Davide; Sartucci, Ferdinando; Giulio, Camillo Di; Domenici, Luciano

    2016-01-01

    The mechanism of the natural aging of olfaction and its declinein the absence of any overt disease conditions remains unclear. Here, we investigated this mechanism through measurement of one of the parameters of olfactory function, the absolute threshold, in a healthy population from childhood to old age. The absolute olfactory threshold data were collected from an Italian observational study with 622 participants aged 5-105 years. A subjective testing procedure of constant stimuli was used, which was also compared to the ‘staircase’ method, with the calculation of the reliability. The n-butanol stimulus was used as an ascending series of nine molar concentrations that were monitored using an electronic nose. The data were analyzed using nonparametric statistics because of the multimodal distribution. We show that the age-related variations in the absolute olfactory threshold are not continuous; instead, there are multiple olfactory phenotypes. Three distinct age-related phenotypes were defined, termed as ‘juvenile’, ‘mature’ and ‘elder’. The frequency of these three phenotypes depends on age. Our data suggest that the sense of smell does not decrease linearly with aging. Our findings provide the basis for further understanding of olfactory loss as an anticipatory sign of aging and neurodegenerative processes. PMID:27027240

  16. Olfactory coding in the honeybee lateral horn.

    PubMed

    Roussel, Edith; Carcaud, Julie; Combe, Maud; Giurfa, Martin; Sandoz, Jean-Christophe

    2014-03-03

    Olfactory systems dynamically encode odor information in the nervous system. Insects constitute a well-established model for the study of the neural processes underlying olfactory perception. In insects, odors are detected by sensory neurons located in the antennae, whose axons project to a primary processing center, the antennal lobe. There, the olfactory message is reshaped and further conveyed to higher-order centers, the mushroom bodies and the lateral horn. Previous work has intensively analyzed the principles of olfactory processing in the antennal lobe and in the mushroom bodies. However, how the lateral horn participates in olfactory coding remains comparatively more enigmatic. We studied odor representation at the input to the lateral horn of the honeybee, a social insect that relies on both floral odors for foraging and pheromones for social communication. Using in vivo calcium imaging, we show consistent neural activity in the honeybee lateral horn upon stimulation with both floral volatiles and social pheromones. Recordings reveal odor-specific maps in this brain region as stimulations with the same odorant elicit more similar spatial activity patterns than stimulations with different odorants. Odor-similarity relationships are mostly conserved between antennal lobe and lateral horn, so that odor maps recorded in the lateral horn allow predicting bees' behavioral responses to floral odorants. In addition, a clear segregation of odorants based on pheromone type is found in both structures. The lateral horn thus contains an odor-specific map with distinct representations for the different bee pheromones, a prerequisite for eliciting specific behaviors.

  17. Chemical olfactory signals and parenthood in mammals.

    PubMed

    Corona, Rebeca; Lévy, Frédéric

    2015-02-01

    This article is part of a Special Issue "Chemosignals and Reproduction". In mammalian species, odor cues emitted by the newborn are essential to establish maternal behavior at parturition and coordinate early mother-infant interactions. Offspring odors become potent attractive stimuli at parturition promoting the contact with the young to ensure that normal maternal care develops. In some species odors provide a basis for individual recognition of the offspring and highly specialized neural mechanisms for learning the infant signals have evolved. Both the main and the accessory olfactory systems are involved in the onset of maternal care, but only the former contributes to individual odor discrimination of the young. Electrophysiological and neurochemical changes occur in the main olfactory bulb leading to a coding of the olfactory signature of the familiar young. Olfactory neurogenesis could also contribute to motherhood and associated learning. Parturition and interactions with the young influence neurogenesis and some evidence indicates a functional link between olfactory neurogenesis and maternal behavior. Although a simple compound has been found which regulates anogenital licking in the rat, studies identifying the chemical nature of these odors are lacking. Neonatal body odors seem to be particularly salient to human mothers who are able to identify their infant's odors. Recent studies have revealed some neural processing of these cues confirming the importance of mother-young chemical communication in our own species.

  18. Comparative cytokeratin distribution patterns in cholesteatoma epithelium.

    PubMed

    Olszewska, E; Sudhoff, H

    2007-01-01

    Cytokeratins (CKs) are known as the intermediate filament proteins of epithelial origin. Their distribution in human epithelia is different according to the type of epithelium, state of growth and differentiation. We used monoclonal mouse antibodies against cytokeratins to study CK expression in the following human tissues: cholesteatoma, middle ear mucosa, glandular epithelium, and meatal ear canal epithelium. Immunohistochemical processing was performed using the labeled steptavidin peroxidase method to demonstrate the presence of CKs in cells of human epidermis. Positive reaction was obtained for CK4, CK34betaE12, CK10, CK14 in skin and cholesteatoma epithelium. However, a more extensive positive reaction with those CKs was observed in cholesteatoma epithelium. Positive immunoreactivity was seen with anti- CK19 in the glandular epithelium. Middle ear mucosa specimens revealed positive immunoreactivity with the antibodies against CK4. The expression of CK4 was definitely positive within the basal layers of the epidermis. The glandular epithelium showed no positive reaction with anti- CK4, anti- CK34betaE12, anti- CK14 and anti-CK10. Immunohistochemistry for CK18 showed no reaction in all examined tissues. Cholesteatoma is known as a proliferative disease in the middle ear which pathogenesis is not completely understood. Keratinocytes express hyperproliferation- associated CKs and after reaching the suprabasal layers they finally undergo apoptosis creating keratinous debris. Cytokeratin expression observed in the epithelium explains proliferative behavior of cholesteatoma which is associated with increased keratinocyte migration. Cytokeratins can be used as potential proliferative markers. It can also allow for searching the usefulness of inhibiting regulators in the treatment of hyperproliferative diseases.

  19. Osmotic regulation of airway reactivity by epithelium.

    PubMed

    Fedan, J S; Yuan, L X; Chang, V C; Viola, J O; Cutler, D; Pettit, L L

    1999-05-01

    Inhalation of nonisotonic solutions can elicit pulmonary obstruction in asthmatic airways. We evaluated the hypothesis that the respiratory epithelium is involved in responses of the airways to nonisotonic solutions using the guinea pig isolated, perfused trachea preparation to restrict applied agents to the mucosal (intraluminal) or serosal (extraluminal) surface of the airway. In methacholine-contracted tracheae, intraluminally applied NaCl or KCl equipotently caused relaxation that was unaffected by the cyclo-oxygenase inhibitor, indomethacin, but was attenuated by removal of the epithelium and Na+ and Cl- channel blockers. Na+-K+-2Cl- cotransporter and nitric oxide synthase blockers caused a slight inhibition of relaxation, whereas Na+,K+-pump inhibition produced a small potentiation. Intraluminal hyperosmolar KCl and NaCl inhibited contractions in response to intra- or extraluminally applied methacholine, as well as neurogenic cholinergic contractions elicited with electric field stimulation (+/- indomethacin). Extraluminally applied NaCl and KCl elicited epithelium-dependent relaxation (which for KCl was followed by contraction). In contrast to the effects of hyperosmolarity, intraluminal hypo-osmolarity caused papaverine-inhibitable contractions (+/- epithelium). These findings suggest that the epithelium is an osmotic sensor which, through the release of epithelium-derived relaxing factor, can regulate airway diameter by modulating smooth muscle responsiveness and excitatory neurotransmission.

  20. Application of artificial neural networks on mosquito Olfactory Receptor Neurons for an olfactory biosensor.

    PubMed

    Bachtiar, Luqman R; Unsworth, Charles P; Newcomb, Richard D

    2013-01-01

    Various odorants such as carbon dioxide (CO2) and 1-octen-3-ol, underlie the host-seeking behaviors of the major malaria vector Anopheles Gambiae. Highlighted by the olfactory processing strength of the mosquito, such a powerful olfactory sense could serve as the sensors of an artificial olfactory biosensor. In this work, we use the firing rates of the A. Gambiae mosquito Olfactory Receptor Neurons (ORNs), to train an Artificial Neural Network (ANN) for the classification of volatile odorants into their known chemical classes and assess their suitability for an olfactory biosensor. With the implementation of bootstrapping, a more representative result was obtained wherein we demonstrate the training of a hybrid ANN consisting of an array of Multi-Layer Perceptrons (MLPs) with optimal number of hidden neurons. The ANN system was able to correctly class 90.1% of the previously unseen odorants, thus demonstrating very strong evidence for the use of A. Gambiae olfactory receptors coupled with an ANN as an olfactory biosensor.

  1. Neural Correlates of Olfactory Learning: Critical Role of Centrifugal Neuromodulation

    ERIC Educational Resources Information Center

    Fletcher, Max L.; Chen, Wei R.

    2010-01-01

    The mammalian olfactory system is well established for its remarkable capability of undergoing experience-dependent plasticity. Although this process involves changes at multiple stages throughout the central olfactory pathway, even the early stages of processing, such as the olfactory bulb and piriform cortex, can display a high degree of…

  2. Individual olfactory perception reveals meaningful nonolfactory genetic information.

    PubMed

    Secundo, Lavi; Snitz, Kobi; Weissler, Kineret; Pinchover, Liron; Shoenfeld, Yehuda; Loewenthal, Ron; Agmon-Levin, Nancy; Frumin, Idan; Bar-Zvi, Dana; Shushan, Sagit; Sobel, Noam

    2015-07-14

    Each person expresses a potentially unique subset of ∼ 400 different olfactory receptor subtypes. Given that the receptors we express partially determine the odors we smell, it follows that each person may have a unique nose; to capture this, we devised a sensitive test of olfactory perception we termed the "olfactory fingerprint." Olfactory fingerprints relied on matrices of perceived odorant similarity derived from descriptors applied to the odorants. We initially fingerprinted 89 individuals using 28 odors and 54 descriptors. We found that each person had a unique olfactory fingerprint (P < 10(-10)), which was odor specific but descriptor independent. We could identify individuals from this pool using randomly selected sets of 7 odors and 11 descriptors alone. Extrapolating from this data, we determined that using 34 odors and 35 descriptors we could individually identify each of the 7 billion people on earth. Olfactory perception, however, fluctuates over time, calling into question our proposed perceptual readout of presumably stable genetic makeup. To test whether fingerprints remain informative despite this temporal fluctuation, building on the linkage between olfactory receptors and HLA, we hypothesized that olfactory perception may relate to HLA. We obtained olfactory fingerprints and HLA typing for 130 individuals, and found that olfactory fingerprint matching using only four odorants was significantly related to HLA matching (P < 10(-4)), such that olfactory fingerprints can save 32% of HLA tests in a population screen (P < 10(-6)). In conclusion, a precise measure of olfactory perception reveals meaningful nonolfactory genetic information.

  3. Reading cinnamon activates olfactory brain regions.

    PubMed

    González, Julio; Barros-Loscertales, Alfonso; Pulvermüller, Friedemann; Meseguer, Vanessa; Sanjuán, Ana; Belloch, Vicente; Avila, César

    2006-08-15

    Some words immediately and automatically remind us of odours, smells and scents, whereas other language items do not evoke such associations. This study investigated, for the first time, the abstract linking of linguistic and odour information using modern neuroimaging techniques (functional MRI). Subjects passively read odour-related words ('garlic', 'cinnamon', 'jasmine') and neutral language items. The odour-related terms elicited activation in the primary olfactory cortex, which include the piriform cortex and the amygdala. Our results suggest the activation of widely distributed cortical cell assemblies in the processing of olfactory words. These distributed neuron populations extend into language areas but also reach some parts of the olfactory system. These distributed neural systems may be the basis of the processing of language elements, their related conceptual and semantic information and the associated sensory information.

  4. Manganese uptake and distribution in the brain after methyl bromide-induced lesions in the olfactory epithelia.

    PubMed

    Thompson, Khristy J; Molina, Ramon M; Donaghey, Thomas; Savaliya, Sandeep; Schwob, James E; Brain, Joseph D

    2011-03-01

    Manganese (Mn) is an essential nutrient with potential neurotoxic effects. Mn deposited in the nose is apparently transported to the brain through anterograde axonal transport, bypassing the blood-brain barrier. However, the role of the olfactory epithelial cells in Mn transport from the nasal cavity to the blood and brain is not well understood. We utilized the methyl bromide (MeBr) lesion model wherein the olfactory epithelium fully regenerates in a time-dependent and cell type-specific manner over the course of 6-8 weeks postinjury. We instilled (54)MnCl(2) intranasally at different recovery periods to study the role of specific olfactory epithelial cell types in Mn transport. (54)MnCl(2) was instilled at 2, 4, 7, 21, and 56 days post-MeBr treatment. (54)Mn concentrations in the blood were measured over the first 4-h period and in the brain and other tissues at 7 days postinstillation. Age-matched control rats were similarly studied at 2 and 56 days. Blood and tissue (54)Mn levels were reduced initially but returned to control values by day 7 post-MeBr exposure, coinciding with the reestablishment of sustentacular cells. Brain (54)Mn levels also decreased but returned to control levels only by 21 days, the period near the completion of neuronal regeneration/bulbar reinnervation. Our data show that Mn transport to the blood and brain temporally correlated with olfactory epithelial regeneration post-MeBr injury. We conclude that (1) sustentacular cells are necessary for Mn transport to the blood and (2) intact axonal projections are required for Mn transport from the nasal cavity to the olfactory bulb and brain.

  5. BDNF over-expression increases olfactory bulb granule cell dendritic spine density in vivo

    PubMed Central

    McDole, Brittnee; Isgor, Ceylan; Pare, Christopher; Guthrie, Kathleen

    2015-01-01

    Olfactory bulb granule cells are axon-less, inhibitory interneurons that regulate the activity of the excitatory output neurons, the mitral and tufted cells, through reciprocal dendrodendritic synapses located on granule cell spines. These contacts are established in the distal apical dendritic compartment, while granule cell basal dendrites and more proximal apical segments bear spines that receive glutamatergic inputs from the olfactory cortices. This synaptic connectivity is vital to olfactory circuit function and is remodeled during development, and in response to changes in sensory activity and lifelong granule cell neurogenesis. Manipulations that alter levels of the neurotrophin brain-derived neurotrophic factor (BDNF) in vivo have significant effects on dendritic spine morphology, maintenance and activity-dependent plasticity for a variety of CNS neurons, yet little is known regarding BDNF effects on bulb granule cell spine maturation or maintenance. Here we show that, in vivo, sustained bulbar over-expression of BDNF produces a marked increase in granule cell spine density that includes an increase in mature spines on their apical dendrites. Morphometric analysis demonstrated that changes in spine density were most notable in the distal and proximal apical domains, indicating that multiple excitatory inputs are potentially modified by BDNF. Our results indicate that increased levels of endogenous BDNF can promote the maturation and/or maintenance of dendritic spines on granule cells, suggesting a role for this factor in modulating granule cell functional connectivity within adult olfactory circuitry. PMID:26211445

  6. Neuropeptide Y enhances olfactory mucosa responses to odorant in hungry rats.

    PubMed

    Negroni, Julia; Meunier, Nicolas; Monnerie, Régine; Salesse, Roland; Baly, Christine; Caillol, Monique; Congar, Patrice

    2012-01-01

    Neuropeptide Y (NPY) plays an important role in regulating appetite and hunger in vertebrates. In the hypothalamus, NPY stimulates food intake under the control of the nutritional status. Previous studies have shown the presence of NPY and receptors in rodent olfactory system, and suggested a neuroproliferative role. Interestingly, NPY was also shown to directly modulate olfactory responses evoked by a food-related odorant in hungry axolotls. We have recently demonstrated that another nutritional cue, insulin, modulates the odorant responses of the rat olfactory mucosa (OM). Therefore, the aim of the present study was to investigate the potential effect of NPY on rat OM responses to odorants, in relation to the animal's nutritional state. We measured the potential NPY modulation of OM responses to odorant, using electro-olfactogram (EOG) recordings, in fed and fasted adult rats. NPY application significantly and transiently increased EOG amplitudes in fasted but not in fed rats. The effects of specific NPY-receptor agonists were similarly quantified, showing that NPY operated mainly through Y1 receptors. These receptors appeared as heterogeneously expressed by olfactory neurons in the OM, and western blot analysis showed that they were overexpressed in fasted rats. These data provide the first evidence that NPY modulates the initial events of odorant detection in the rat OM. Because this modulation depends on the nutritional status of the animal, and is ascribed to NPY, the most potent orexigenic peptide in the central nervous system, it evidences a strong supplementary physiological link between olfaction and nutritional processes.

  7. Neuropeptide Y Enhances Olfactory Mucosa Responses to Odorant in Hungry Rats

    PubMed Central

    Negroni, Julia; Meunier, Nicolas; Monnerie, Régine; Salesse, Roland; Baly, Christine; Caillol, Monique; Congar, Patrice

    2012-01-01

    Neuropeptide Y (NPY) plays an important role in regulating appetite and hunger in vertebrates. In the hypothalamus, NPY stimulates food intake under the control of the nutritional status. Previous studies have shown the presence of NPY and receptors in rodent olfactory system, and suggested a neuroproliferative role. Interestingly, NPY was also shown to directly modulate olfactory responses evoked by a food-related odorant in hungry axolotls. We have recently demonstrated that another nutritional cue, insulin, modulates the odorant responses of the rat olfactory mucosa (OM). Therefore, the aim of the present study was to investigate the potential effect of NPY on rat OM responses to odorants, in relation to the animal's nutritional state. We measured the potential NPY modulation of OM responses to odorant, using electro-olfactogram (EOG) recordings, in fed and fasted adult rats. NPY application significantly and transiently increased EOG amplitudes in fasted but not in fed rats. The effects of specific NPY-receptor agonists were similarly quantified, showing that NPY operated mainly through Y1 receptors. These receptors appeared as heterogeneously expressed by olfactory neurons in the OM, and western blot analysis showed that they were overexpressed in fasted rats. These data provide the first evidence that NPY modulates the initial events of odorant detection in the rat OM. Because this modulation depends on the nutritional status of the animal, and is ascribed to NPY, the most potent orexigenic peptide in the central nervous system, it evidences a strong supplementary physiological link between olfaction and nutritional processes. PMID:23024812

  8. Asymmetrical Processing of Olfactory Input in the Piriform Cortex Mediates "Activation" of the Avian Navigation Circuitry.

    PubMed

    Jorge, Paulo E; Marques, Paulo A M; Pinto, Belmiro V; Phillips, John B

    2016-08-11

    The role of odors in the long-distance navigation of birds has elicited intense debate for more than half a century. Failure to resolve many of the issues fueling this debate is due at least in part to the absence of controls for a variety of non-specific effects that odors have on the navigational process. The present experiments were carried out to investigate whether the olfactory inputs are involved only in "activation" of neuronal circuitry involved in navigation or are also playing a role in providing directional information. Experienced adult pigeons were exposed to controlled olfactory stimuli during different segments of the journey (release site vs. displacement + release site). Protein levels of IEGs (immediate early genes used to mark synaptic activity) were analyzed in areas within the olfactory/navigation avian circuitry. The results indicate that 1) exposure to natural odors at the release site (and not before) elicit greater activation across brain regions than exposure to filtered air, artificial odors, and natural odors along the entire outward journey (from home to the release site, inclusive); 2) activation of the piriform cortex in terms of odor discrimination is lateralized; 3) activation of the navigation circuitry is achieved by means of lateralized activation of piriform cortex neurons. Altogether, the findings provide the first direct evidence that activation of the avian navigation circuitry is mediated by asymmetrical processing of olfactory input occurring in the right piriform cortex.

  9. BDNF over-expression increases olfactory bulb granule cell dendritic spine density in vivo.

    PubMed

    McDole, B; Isgor, C; Pare, C; Guthrie, K

    2015-09-24

    Olfactory bulb granule cells (GCs) are axon-less, inhibitory interneurons that regulate the activity of the excitatory output neurons, the mitral and tufted cells, through reciprocal dendrodendritic synapses located on GC spines. These contacts are established in the distal apical dendritic compartment, while GC basal dendrites and more proximal apical segments bear spines that receive glutamatergic inputs from the olfactory cortices. This synaptic connectivity is vital to olfactory circuit function and is remodeled during development, and in response to changes in sensory activity and lifelong GC neurogenesis. Manipulations that alter levels of the neurotrophin brain-derived neurotrophic factor (BDNF) in vivo have significant effects on dendritic spine morphology, maintenance and activity-dependent plasticity for a variety of CNS neurons, yet little is known regarding BDNF effects on bulb GC spine maturation or maintenance. Here we show that, in vivo, sustained bulbar over-expression of BDNF in transgenic mice produces a marked increase in GC spine density that includes an increase in mature spines on their apical dendrites. Morphometric analysis demonstrated that changes in spine density were most notable in the distal and proximal apical domains, indicating that multiple excitatory inputs are potentially modified by BDNF. Our results indicate that increased levels of endogenous BDNF can promote the maturation and/or maintenance of dendritic spines on GCs, suggesting a role for this factor in modulating GC functional connectivity within adult olfactory circuitry.

  10. Plasticity in the olfactory bulb of the maternal mouse is prevented by gestational stress

    PubMed Central

    Belnoue, Laure; Malvaut, Sarah; Ladevèze, Elodie; Abrous, Djoher Nora; Koehl, Muriel

    2016-01-01

    Maternal stress is associated with an altered mother-infant relationship that endangers offspring development, leading to emotional/behavioral problems. However, little research has investigated the stress-induced alterations of the maternal brain that could underlie such a disruption of mother-infant bonding. Olfactory cues play an extensive role in the coordination of mother-infant interactions, suggesting that motherhood may be associated to enhanced olfactory performances, and that this effect may be abolished by maternal stress. To test this hypothesis, we analyzed the impact of motherhood under normal conditions or after gestational stress on olfactory functions in C57BL/6 J mice. We report that gestational stress alters maternal behavior and prevents both mothers’ ability to discriminate pup odors and motherhood-induced enhancement in odor memory. We investigated adult bulbar neurogenesis as a potential mechanism of the enhanced olfactory function in mothers and found that motherhood was associated with an increased complexity of the dendritic tree of newborn neurons. This motherhood-evoked remodeling was totally prevented by gestational stress. Altogether, our results may thus provide insight into the neural changes that could contribute to altered maternal behavior in stressed mothers. PMID:27886228

  11. Drosophila TRPA channel painless inhibits male-male courtship behavior through modulating olfactory sensation.

    PubMed

    Wang, Kaiyu; Guo, Yanmeng; Wang, Fei; Wang, Zuoren

    2011-01-01

    The Drosophila melanogaster TRPA family member painless, expressed in a subset of multidendritic neurons embeding in the larval epidermis, is necessary for larval nociception of noxious heat or mechanical stimuli. However, the function of painless in adult flies remains largely unknown. Here we report that mutation of painless leads to a defect in male-male courtship behavior and alteration in olfaction sensitivity in adult flies. Specific downregulation of the expression of the Painless protein in the olfactory projection neurons (PNs) of the antennal lobes (ALs) resulted in a phenotype resembling that found in painless mutant flies, whereas overexpression of Painless in PNs of painless mutant males suppressed male-male courtship behavior. The downregulation of Painless exclusively during adulthood also resulted in male-male courtship behavior. In addition, mutation of the painless gene in flies caused changes in olfaction, suggesting a role for this gene in olfactory processing. These results indicate that functions of painless in the adult central nervous system of Drosophila include modulation of olfactory processing and inhibition of male-male courtship behavior.

  12. Olfactory regulation of mosquito–host interactions

    PubMed Central

    Zwiebel, L.J.; Takken, W.

    2011-01-01

    Mosquitoes that act as disease vectors rely upon olfactory cues to direct several important behaviors that are fundamentally involved in establishing their overall vectorial capacity. Of these, the propensity to select humans for blood feeding is arguably the most important of these olfactory driven behaviors in so far as it significantly contributes to the ability of these mosquitoes to transmit pathogens that cause diseases such as dengue, yellow fever and most significantly human malaria. Here, we review significant advances in behavioral, physiological and molecular investigations into mosquito host preference, with a particular emphasis on studies that have emerged in the post-genomic era that seek to combine these approaches. PMID:15242705

  13. Foxg1 promotes olfactory neurogenesis by antagonizing Gdf11

    PubMed Central

    Kawauchi, Shimako; Kim, Joon; Santos, Rosaysela; Wu, Hsiao-Huei; Lander, Arthur D.; Calof, Anne L.

    2009-01-01

    Summary Foxg1, a winged-helix transcription factor, promotes the development of anterior neural structures; in mice lacking Foxg1, development of the cerebral hemispheres and olfactory epithelium (OE) is severely reduced. It has been suggested that Foxg1 acts by positively regulating the expression of growth factors, such as Fgf8, which support neurogenesis. However, Foxg1 also binds Smad transcriptional complexes, allowing it to negatively regulate the effects of TGFβ family ligands. Here, we provide evidence that this latter effect explains much of the ability of Foxg1 to drive neurogenesis in the OE. We show that Foxg1 is expressed in developing OE at the same time as the gene encoding growth differentiation factor 11 (Gdf11), a TGFβ family member that mediates negative-feedback control of OE neurogenesis. Mutations in Gdf11 rescue, to a considerable degree, the major defects in Foxg1-/- OE, including the early, severe loss of neural precursors and olfactory receptor neurons, and the subsequent collapse of both neurogenesis and nasal cavity formation. Rescue is gene-dosage dependent, with loss of even one allele of Gdf11 restoring substantial neurogenesis. Notably, we find no evidence for a disruption of Fgf8 expression in Foxg1-/- OE. However, we do observe both a failure of expression of follistatin (Fst), which encodes a secreted Gdf11 antagonist normally expressed in and around OE, and an increase in the expression of Gdf11 itself within the remaining OE in these mutants. Fst expression is rescued in Foxg1-/-;Gdf11-/- and Foxg1-/-;Gdf11+/- mice. These data suggest that the influence of Foxg1 on Gdf11-mediated negative feedback of neurogenesis may be both direct and indirect. In addition, defects in development of the cerebral hemispheres in Foxg1-/- mice are not rescued by mutations in Gdf11, nor is Gdf11 expressed at high levels within these structures. Thus, the pro-neurogenic effects of Foxg1 are likely to be mediated through different signaling

  14. Morphological, olfactory, and vocal development in big brown bats

    PubMed Central

    Mayberry, Heather W.; Faure, Paul A.

    2015-01-01

    ABSTRACT Using a within subjects design, we documented morphological, bioacoustical and behavioral developmental changes in big brown bats. Eptesicus fuscus pups are born naked and blind but assume an adult-like appearance by post-natal day (PND) 45 and flight by PND 30. Adult females use spatial memory, acoustic and olfactory cues to reunite with offspring, but it is unclear if pups can recognize maternal scents. We tested the olfactory discrimination abilities of young E. fuscus pups and found they exhibited no odor preferences. Pups also emit distinct vocalizations called isolation calls (i-calls) that facilitate mother-offspring reunions, but how pups shift their vocalizations from i-calls to downward frequency modulated (FM) sweeps used in echolocation remains unclear. Between PND 0–9, pups emitted mainly long duration, tonal i-calls rich in harmonics, but after they switched to short duration, downward FM sweeps with fewer harmonics. Call maximum frequency and repetition rate showed minor changes across development. Signal duration, bandwidth, and number of harmonics decreased, whereas the maximum, minimum and bandwidth of the fundamental, and peak spectral frequency all increased. We recorded vocalizations during prolonged maternal separation and found that isolated pups called longer and at a faster rate, presumably to signal for maternal assistance. To assess how PND 13 pups alter their signals during interactions with humans we compared spontaneous and provoked vocalizations and found that provoked calls were spectrally and temporally more similar to those of younger bats suggesting that pups in distress emit signals that sound like younger bats to promote maternal assistance. PMID:25505151

  15. Structure and diversity in mammalian accessory olfactory bulb.

    PubMed

    Meisami, E; Bhatnagar, K P

    1998-12-15

    The accessory olfactory bulb (AOB) is the first neural integrative center for the olfactory-like vomeronasal sensory system. In this article, we first briefly present an overview of vomeronasal system organization and review the history of the discovery of mammalian AOB. Next, we briefly review the evolution of the vomeronasal system in vertebrates, in particular the reptiles. Following these introductory aspects, the structure of the rodent AOB, as typical of the well-developed mammalian AOB, is presented, detailing laminar organization and cell types as well as aspects of the homology with the main olfactory bulb. Then, the evolutionary origin and diversity of the AOB in mammalian orders and species is discussed, describing structural, phylogenetic, and species-specific variation in the AOB location, shape, and size and morphologic differentiation and development. The AOB is believed to be absent in fishes but present in terrestrial tetrapods including amphibians; among the reptiles AOB is absent in crocodiles, present in turtles, snakes, and some lizards where it may be as large or larger than the main bulb. The AOB is absent in bird and in the aquatic mammals (whales, porpoises, manatees). Among other mammals, AOB is present in the monotremes and marsupials, edentates, and in the majority of the placental mammals like carnivores, herbivores, as well as rodents and lagomorphs. Most bat species do not have an AOB and among those where one is found, it shows marked variation in size and morphologic development. Among insectivores and primates, AOB shows marked variation in occurrence, size, and morphologic development. It is small in shrews and moles, large in hedgehogs and prosimians; AOB continues to persist in New World monkeys but is not found in the adults of the higher primates such as the Old World monkeys, apes, and humans. In many species where AOB is absent in the adult, it often develops in the embryo and fetus but regresses in later stages of

  16. Olfactory sensations produced by high-energy photon irradiation of the olfactory receptor mucosa in humans

    SciTech Connect

    Sagar, S.M.; Thomas, R.J.; Loverock, L.T.; Spittle, M.F. )

    1991-04-01

    During irradiation of volumes that incorporate the olfactory system, a proportion of patients have complained of a pungent smell. A retrospective study was carried out to determine the prevalence of this side-effect. A questionnaire was sent to 40 patients whose treatment volumes included the olfactory region and also to a control group treated away from this region. The irradiated tumor volumes included the frontal lobe, whole brain, nasopharynx, pituitary fossa, and maxillary antrum. Of the 25 patients who replied, 60% experienced odorous symptoms during irradiation. They described the odor as unpleasant and consistent with ozone. Stimulation of olfactory receptors is considered to be caused by the radiochemical formation of ozone and free radicals in the mucus overlying the olfactory mucosa.

  17. In vitro differentiation of neural stem cells derived from human olfactory bulb into dopaminergic-like neurons.

    PubMed

    Alizadeh, Rafieh; Hassanzadeh, Gholamreza; Joghataei, Mohammad Taghi; Soleimani, Mansoureh; Moradi, Fatemeh; Mohammadpour, Shahram; Ghorbani, Jahangir; Safavi, Ali; Sarbishegi, Maryam; Pirhajati Mahabadi, Vahid; Alizadeh, Leila; Hadjighassem, Mahmoudreza

    2017-03-01

    This study describes a new accessible source of neuronal stem cells that can be used in Parkinson's disease cell transplant. The human olfactory bulb contains neural stem cells (NSCs) that are responsible for neurogenesis in the brain and the replacement of damaged cellular components throughout life. NSCs are capable of differentiating into neuronal and glial cells. We isolated NSCs from the olfactory bulb of brain-death donors and differentiated them into dopaminergic neurons. The olfactory bulb tissues obtained were cultured in Dulbecco's modified Eagle's medium/nutrient mixture F12, B27 supplemented with basic fibroblast growth factor, epidermal growth factor and leukemia inhibitory factor. The NSCs and proliferation markers were assessed. The multipotentiality of olfactory bulb NSCs was demonstrated by their capacity to differentiate into neurons, oligodendrocytes and astrocytes. To generate dopaminergic neurons, olfactory bulb NSCs were differentiated in neurobasal medium, supplemented with B27, and treated with sonic hedgehog, fibroblast growth factor 8 and glial cell-derived neurotrophic factor from the 7th to the 21st day, followed by detection of dopaminergic neuronal markers including tyrosine hydroxylase and aromatic l-amino acid decarboxylase. The cells were expanded, established in continuous cell lines and differentiated into the two classical neuronal phenotypes. The percentage of co-positive cells (microtubule-associated protein 2 and tyrosine hydroxylase; aromatic l-amino acid decarboxylase and tyrosine hydroxylase) in the treated cells was significantly higher than in the untreated cells. These results illustrate the existence of multipotent NSCs in the adult human olfactory bulb that are capable of differentiating toward putative dopaminergic neurons in the presence of trophic factors. Taken together, our data encourage further investigations of the possible use of olfactory bulb NSCs as a promising cell-based therapeutic strategy for Parkinson

  18. Shh-proteoglycan interactions regulate maturation of olfactory glomerular circuitry.

    PubMed

    Persson, Laura; Witt, Rochelle M; Galligan, Meghan; Greer, Paul L; Eisner, Adriana; Pazyra-Murphy, Maria F; Datta, Sandeep R; Segal, Rosalind A

    2014-12-01

    The olfactory system relies on precise circuitry connecting olfactory sensory neurons (OSNs) and appropriate relay and processing neurons of the olfactory bulb (OB). In mammals, the exact correspondence between specific olfactory receptor types and individual glomeruli enables a spatially precise map of glomerular activation that corresponds to distinct odors. However, the mechanisms that govern the establishment and maintenance of the glomerular circuitry are largely unknown. Here we show that high levels of Sonic Hedgehog (Shh) signaling at multiple sites enable refinement and maintenance of olfactory glomerular circuitry. Mice expressing a mutant version of Shh (Shh(Ala/Ala)), with impaired binding to proteoglycan co-receptors, exhibit disproportionately small olfactory bulbs containing fewer glomeruli. Notably, in mutant animals the correspondence between individual glomeruli and specific olfactory receptors is lost, as olfactory sensory neurons expressing different olfactory receptors converge on the same glomeruli. These deficits arise at late stages in post-natal development and continue into adulthood, indicating impaired pruning of erroneous connections within the olfactory bulb. In addition, mature Shh(Ala/Ala) mice exhibit decreased proliferation in the subventricular zone (SVZ), with particular reduction in neurogenesis of calbindin-expressing periglomerular cells. Thus, Shh interactions with proteoglycan co-receptors function at multiple locations to regulate neurogenesis and precise olfactory connectivity, thereby promoting functional neuronal circuitry.

  19. Shh-Proteoglycan Interactions Regulate Maturation of Olfactory Glomerular Circuitry

    PubMed Central

    Persson, Laura; Witt, Rochelle M.; Galligan, Meghan; Greer, Paul L.; Eisner, Adriana; Pazyra-Murphy, Maria F.; Datta, Sandeep R.; Segal, Rosalind A.

    2014-01-01

    The olfactory system relies on precise circuitry connecting olfactory sensory neurons (OSNs) and appropriate relay and processing neurons of the olfactory bulb (OB). In mammals, the exact correspondence between specific olfactory receptor types and individual glomeruli enables a spatially precise map of glomerular activation that corresponds to distinct odors. However, the mechanisms that govern the establishment and maintenance of the glomerular circuitry are largely unknown. Here we show that high levels of Sonic Hedgehog (Shh) signaling at multiple sites enable refinement and maintenance of olfactory glomerular circuitry. Mice expressing a mutant version of Shh (ShhAla/Ala), with impaired binding to proteoglycan co-receptors, exhibit disproportionately small olfactory bulbs containing fewer glomeruli. Notably, in mutant animals the correspondence between individual glomeruli and specific olfactory receptors is lost, as olfactory sensory neurons expressing different olfactory receptors converge on the same glomeruli. These deficits arise at late stages in post-natal development and continue into adulthood, indicating impaired pruning of erroneous connections within the olfactory bulb. In addition, mature ShhAla/Ala mice exhibit decreased proliferation in the subventricular zone (SVZ), with particular reduction in neurogenesis of calbindin-expressing periglomerular cells. Thus, Shh interactions with proteoglycan co-receptors function at multiple locations to regulate neurogenesis and precise olfactory connectivity, thereby promoting functional neuronal circuitry. PMID:24913191

  20. On the organization of olfactory and vomeronasal cortices.

    PubMed

    Martinez-Marcos, Alino

    2009-01-12

    Classically, the olfactory and vomeronasal pathways are thought to run in parallel non-overlapping axes in the forebrain subserving different functions. The olfactory and vomeronasal epithelia project to the main and accessory olfactory bulbs (primary projections), which in turn project to different areas of the telencephalon in a non-topographic fashion (secondary projections) and so on (tertiary projections). New data indicate that projections arising from the main and accessory olfactory bulbs converge widely in the rostral basal telencephalon. In contrast, in the vomeronasal system, cloning two classes of vomeronasal receptors (V1R and V2R) has led to the distinction of two anatomically and functionally independent pathways that reach some common, but also some different, targets in the amygdala. Tertiary projections from the olfactory and vomeronasal amygdalae are directed to the ventral striatum, which thus becomes a site for processing and potential convergence of chemosensory stimuli. Functional data indicate that the olfactory and vomeronasal systems are able to detect and process volatiles (presumptive olfactory cues) as well as pheromones in both epithelia and bulbs. Collectively, these data indicate that the anatomical and functional distinction between the olfactory and vomeronasal systems should be re-evaluated. Specifically, the recipient cortex should be reorganized to include olfactory, vomeronasal (convergent and V1R and V2R specific areas) and mixed (olfactory and vomeronasal) chemosensory cortices. This new perspective could help to unravel olfactory and vomeronasal interactions in behavioral paradigms.

  1. Olfactory perception, communication, and the nose-to-brain pathway.

    PubMed

    Stockhorst, Ursula; Pietrowsky, Reinhard

    2004-10-30

    The present paper's aim is of to give an overview about the basic knowledge as well as actual topics of olfaction--with a special regard on behavior. We summarize different functions of the nose and the olfactory system in human physiology and psychology. We will first describe the functional anatomy of the olfactory system in man. Afterwards, the function of the olfactory system will be viewed from an evolutionary and phylogenetic perspective. We will further outline the main features of olfactory perception, and will show how olfactory perception is influenced by learning. Olfactory signals are relevant stimuli that affect communication. Consequently, the role of the olfactory system in social interaction and mood will be described and gender differences will be addressed. Finally, the function of the nose as an interface to the brain, including implications for pharmacology, will be discussed.

  2. Sphenoid esthesioneuroblastoma arising from the hindmost olfactory filament.

    PubMed

    Matsunaga, Mami; Nakagawa, Takayuki; Sakamoto, Tatsunori; Ito, Juichi

    2015-04-01

    Esthesioneuroblastoma (ENB), or olfactory neuroblastoma, is a rare malignant neoplasm arising from the olfactory neuroepithelium. Typically, ENBs are found in the olfactory cleft with extension to the ethmoid sinuses or anterior skull base. Here we report a case of ENB located in the sphenoid sinus, which had been considered as an ectopic ENB. However, endoscopic resection revealed the continuity of the tumor with the hindmost olfactory filament. The present case suggests that an ENB in the sphenoid sinus was not ectopic, but arose from the normal olfactory neuroepithelium. This continuity of the ENB with this filament indicated that the tumor was not ectopic, and that there was possible tumor invasion into the olfactory neuroepithelium in the cribriform niche. Therefore, pathological examination of the olfactory neuroepithelium in the cribriform niche may be necessary in case of sphenoid ENBs.

  3. Functional Neuroanatomy of "Drosophila" Olfactory Memory Formation

    ERIC Educational Resources Information Center

    Guven-Ozkan, Tugba; Davis, Ronald L.

    2014-01-01

    New approaches, techniques and tools invented over the last decade and a half have revolutionized the functional dissection of neural circuitry underlying "Drosophila" learning. The new methodologies have been used aggressively by researchers attempting to answer three critical questions about olfactory memories formed with appetitive…

  4. Propagation of olfactory information in Drosophila.

    PubMed

    Root, Cory M; Semmelhack, Julia L; Wong, Allan M; Flores, Jorge; Wang, Jing W

    2007-07-10

    Investigating how information propagates between layers in the olfactory system is an important step toward understanding the olfactory code. Each glomerular output projection neuron (PN) receives two sources of input: the olfactory receptor neurons (ORNs) of the same glomerulus and interneurons that innervate many glomeruli. We therefore asked how these inputs interact to produce PN output. We used receptor gene mutations to silence all of the ORNs innervating a specific glomerulus and recorded PN activity with two-photon calcium imaging and electrophysiology. We found evidence for balanced excitatory and inhibitory synaptic inputs but saw little or no response in the absence of direct ORN input. We next asked whether any transformation of activity occurs at successive layers of the antennal lobe. We found a strong link between PN firing and dendritic calcium elevation, the latter of which is tightly correlated with calcium activity in ORN axons, supporting the idea of glomerular propagation of olfactory information. Finally, we showed that odors are represented by a sparse population of PNs. Together, these results are consistent with the idea that direct receptor input provides the main excitatory drive to PNs, whereas interneurons modulate PN output. Balanced excitatory and inhibitory interneuron input may provide a mechanism to adjust PN sensitivity.

  5. Olfactory Environment Design for Human Spaceflight

    NASA Astrophysics Data System (ADS)

    Welch, C. S.; Holland, F. J.

    2002-01-01

    Smell is usually deemed the least important of the five senses. To contradict this assertion, however, there is no shortage of scientific literature which concludes that olfaction is of very great significance to humans. Odours have been shown to have a variety of effects on humans, and are capable of changing both behaviour and cognitive processing in ways that we are frequently completely unconscious of. Examples of this include alertness, alteration of mood, capacity for ideation and intellectual performance. To date, the design of human spacecraft has concentrated on making their olfactory environments, where possible, `odour neutral' - that is ensuring that all unpleasant and/or offensive odours are removed. Here it suggested that spacecraft (and other extraterrestrial facilities for human inhabitation) might benefit from having their olfactory environments designed to be `odour positive', that is to use odours and olfaction for the positive benefit of their residents. This paper presents a summary of current olfactory research and considers both its positive and negative implications for humans in space. It then discusses `odour positive' design of spacecraft olfactory environments and the possible benefits accruing from this approach before examining its implications for the architecture of spacecraft environmental control systems.

  6. Acid sensing by the Drosophila olfactory system.

    PubMed

    Ai, Minrong; Min, Soohong; Grosjean, Yael; Leblanc, Charlotte; Bell, Rati; Benton, Richard; Suh, Greg S B

    2010-12-02

    The odour of acids has a distinct quality that is perceived as sharp, pungent and often irritating. How acidity is sensed and translated into an appropriate behavioural response is poorly understood. Here we describe a functionally segregated population of olfactory sensory neurons in the fruitfly, Drosophila melanogaster, that are highly selective for acidity. These olfactory sensory neurons express IR64a, a member of the recently identified ionotropic receptor (IR) family of putative olfactory receptors. In vivo calcium imaging showed that IR64a+ neurons projecting to the DC4 glomerulus in the antennal lobe are specifically activated by acids. Flies in which the function of IR64a+ neurons or the IR64a gene is disrupted had defects in acid-evoked physiological and behavioural responses, but their responses to non-acidic odorants remained unaffected. Furthermore, artificial stimulation of IR64a+ neurons elicited avoidance responses. Taken together, these results identify cellular and molecular substrates for acid detection in the Drosophila olfactory system and support a labelled-line mode of acidity coding at the periphery.

  7. Sex differences in the human olfactory system.

    PubMed

    Garcia-Falgueras, Alicia; Junque, Carme; Giménez, Mónica; Caldú, Xavier; Segovia, Santiago; Guillamon, Antonio

    2006-10-20

    The olfactory system (accessory) implicated in reproductive physiology and behavior in mammals is sexually dimorphic. These brain sex differences present two main characteristics: they are seen in neural circuits related to sexual behavior and sexual physiology and they take one of two opposite morphological patterns (male>female or female>male). The present work reports sex differences in the olfactory system in a large homogeneous sample of men (40) and women (51) using of voxel-based morphology. Gray matter concentration showed sexual dimorphism in several olfactory regions. Women have a higher concentration in the orbitofrontal cortex involving Brodmann's areas 10, 11 and 25 and temporomedial cortex (bilateral hippocampus and right amygdala), as well as their left basal insular cortex. In contrast, men show a higher gray matter concentration in the left entorhinal cortex (Brodmann's area 28), right ventral pallidum, dorsal left insular cortex and a region of the orbitofrontal cortex (Brodmann's area 25). This study supports the hypothesis that the mammalian olfactory system is a sexually dimorphic network and provides a theoretical framework for the morphofunctional approach to sex differences in the human brain.

  8. Immunocytochemical characterisation of olfactory ensheathing cells of zebrafish

    PubMed Central

    Lazzari, Maurizio; Bettini, Simone; Franceschini, Valeria

    2014-01-01

    Continuous lifelong neurogenesis is typical of the vertebrate olfactory system. The regenerative ability of olfactory receptor neurons is dependent on the glial cell type specific to the olfactory pathway, designated ‘olfactory ensheathing cells'. Several studies to date have focused on mammalian olfactory ensheathing cells, owing to their potential roles in cell-based therapy for spinal cord injury repair. However, limited information is available regarding this glial cell type in non-mammalian vertebrates, particularly anamniotes. In the current immunocytochemical study, we analysed the features of olfactory ensheathing cells in the zebrafish, Danio rerio. Fish provide a good model for studying glial cells associated with the olfactory pathway of non-mammalian vertebrates. In particular, zebrafish has numerous valuable features that enable its use as a prime model organism for genetic, neurobiological and developmental studies, as well as toxicology and genomics research. Paraffin sections from decalcified heads of zebrafish were processed immunocytochemically to detect proteins used in the research on mammalian olfactory ensheathing cells, including glial fibrillary acid protein (GFAP), S100, neural cell adhesion molecule (NCAM), polysialylated NCAM (PSA-NCAM), vimentin (VIM), p75NTR and galactin (Gal)-1. Notably, GFAP, S100, NCAM and Gal-1 were clearly observed, whereas no vimentin staining was detected. Weak immunostaining for PSA-NCAM and p75NTR was evident. Moreover the degree of marker expression was not uniform in various tracts of the zebrafish olfactory pathway. The immunostaining patterns of the zebrafish olfactory system are distinct from those of other fish to some extent, suggesting interspecific differences. We also showed that the olfactory pathway of zebrafish expresses markers of mammalian olfactory ensheathing cells. The olfactory systems of vertebrates have similarities but there are also marked variations between them. The issue of whether

  9. Morphologic changes in basal cells during repair of tracheal epithelium.

    PubMed Central

    Wang, C. Z.; Evans, M. J.; Cox, R. A.; Burke, A. S.; Zhu, Q.; Herndon, D. N.; Barrow, R. E.

    1992-01-01

    Basal cells are differentiated with respect to junctional adhesion mechanisms and play a role in attachment of columnar epithelium to the basal lamina. Although much is known about nonciliated and ciliated cell differentiation during the repair process after injury, little is known about the basal cell. We studied the morphology of basal cells and quantitated junctional adhesion structures during repair of tracheal epithelium exposed to toxic cotton smoke. Ten adult ewes were given a smoke injury to a portion of the upper cervical trachea and were killed at 4, 6, 8, 10, and 18 days after injury for morphometric studies. At 4 days, there was a stratified reparative epithelium over the basal lamina, which was two to four cells in depth. The basal cells were identified by their hemidesmosome (HD) attachment to the basal lamina. Basal cells were about 69% larger than controls and flattened rather than columnar. The amount of HD attachment was 192% greater than controls. In contrast, volume density of cytokeratin filaments had decreased about 47%. Basal cells had returned to normal numbers and size and a columnar shape by day 18. The amount of desmosome (D) and HD attachment and volume density of cytokeratins had also reached control levels by day 18. These data indicate that morphology of basal cells changes during the initial stages of reparative regeneration but returns to normal by 18 days. Morphologic changes appear to reflect changes in size of the cell associated with cell division rather than differentiation of recently divided basal cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:1381564

  10. Megalin and cubilin in the human gallbladder epithelium.

    PubMed

    Tsaroucha, Alexandra K; Chatzaki, Ekaterini; Lambropoulou, Maria; Despoudi, Kaliopi; Laftsidis, Prodromos; Charsou, Chara; Polychronidis, Alexandros; Papadopoulos, Nikolaos; Simopoulos, Constantinos E

    2008-09-01

    Although the role of cholesterol absorption by the gallbladder epithelium in gallstone formation is well established, the exact process is poorly understood. Potential candidates for regulation of transepithelial cholesterol transport are suggested to be two large membrane multiple ligand receptors, megalin and cubilin. We studied the expression of these two proteins in both acalculous and calculous human gallbladder epithelia. Adult human gallbladder tissues were received from 21 patients (9 men, 12 women) who had undergone cholecystectomy. The patients were divided into two groups: group A (calculous gallbladder group; 5 men, 6 women; mean age 64.4 +/- 11.1 years) with cholelithiasis, and group B (acalculous gallbladder group; 4 men, 6 women; mean age 55.3 +/- 16.1 years). In the gallbladder tissues megalin and cubilin expression was studied by immunohistochemistry and conventional RT-PCR, and gene expression levels were estimated by real-time RT-PCR. Both megalin and cubilin gene transcripts were found in total RNA preparations from acalculous gallbladder. In contrast, in preparations from calculous gallbladder, none or only one of the proteins was detected. Immunoreactive proteins were detected in the simple columnar acalculous gallbladder epithelium but not in the calculous gallbladder epithelium. Our results show different expression patterns of the two proteins in calculous gallbladders and acalculous gallbladders. In the latter both proteins are expressed, suggesting an association with gallstone formation and implying a putative role of the two proteins in cholesterol endocytosis. In other words, the presence of both proteins may be essential for the prevention of stone formation.

  11. 2-D And 3-D Reconstructions Of The Olfactory System Of The Rat

    NASA Astrophysics Data System (ADS)

    Reisner, Alex H.; Bell, G. A.; Bucholtz, C. A.; Rosenfeld, Dov; Tsui, K. K.

    1989-04-01

    The olfactory system of the rat is a useful model for the study of mammalian sensory systems. However, the anatomy of the nasal epithelium, where the cells responsible for detecting odors are located, is extremely complex. Therefore, we have focused our attention on the development of two- and three-dimensional automated imaging methods. The presentation of pure odorants to the experimental animal together with the injection of [14M-deoxyglucose has been combined with autoradiography of frozen sectioned material. Several approaches have been used to obtain optimal alignments of the digitized images of the sections so as to be able to generate appropriate 2-D and 3-D reconstructions. Such reconstructions allow visualization of the ethmo-turbinal bones (turbinates) and the associated soft tissue and appear to be useful in analyzing and highlighting differential metabolic activity.

  12. Olfactory Categorization: A Developmental Study

    ERIC Educational Resources Information Center

    Valentin, Dominique; Chanquoy, Lucile

    2012-01-01

    This study examined the ability of children to classify fruit and flower odors. We asked four groups of children (4-11 years of age) and a group of adults to identify, categorize, and evaluate the edibility, liking, and typicality of 12 fruit and flower odors. Results showed an increase in interindividual agreement with age for the taxonomic…

  13. Emx2 homeodomain transcription factor interacts with eukaryotic translation initiation factor 4E (eIF4E) in the axons of olfactory sensory neurons.

    PubMed

    Nédélec, Stéphane; Foucher, Isabelle; Brunet, Isabelle; Bouillot, Colette; Prochiantz, Alain; Trembleau, Alain

    2004-07-20

    We report that Emx2 homeogene is expressed at the mRNA and protein levels in the adult mouse olfactory neuroepithelium. As expected for a transcription factor, Emx2 is present in the nucleus of immature and mature olfactory sensory neurons. However, the protein is also detected in the axonal compartment of these neurons, both in the olfactory mucosa axon bundles and in axon terminals within the olfactory bulb. Emx2 axonal staining is heterogeneous, suggesting an association with particles. Subcellular fractionations of olfactory bulb synaptosomes, combined with chemical lesions of olfactory neurons, confirm the presence of Emx2 in axon terminals. Significant amounts of Emx2 protein cosediment with high density synaptosomal subfractions containing eukaryotic translation initiation factor 4E (eIF4E). Nonionic detergents and RNase treatments failed to detach eIF4E and Emx2 from these high-density fractions enriched in vesicles and granular structures. In addition, Emx2 and eIF4E can be coimmunoprecipitated from olfactory mucosa and bulb extracts and interact directly, as demonstrated in pull-down experiments. Emx2 axonal localization, association with high-density particles and interaction with eIF4E strongly suggest that this transcription factor has new nonnuclear functions most probably related to the local control of protein translation in the olfactory sensory neuron axons. Finally, we show that two other brain-expressed homeoproteins, Otx2 and Engrailed 2, also bind eIF4E, indicating that several homeoproteins may modulate eIF4E functions in the developing and adult nervous system.

  14. Transcriptional profiling of olfactory system development identifies distal antenna as a regulator of subset of neuronal fates

    PubMed Central

    Barish, Scott; Li, Qingyun; Pan, Jia W.; Soeder, Charlie; Jones, Corbin; Volkan, Pelin C.

    2017-01-01

    Drosophila uses 50 different olfactory receptor neuron (ORN) classes that are clustered within distinct sensilla subtypes to decipher their chemical environment. Each sensilla subtype houses 1–4 ORN identities that arise through asymmetric divisions of a single sensory organ precursor (SOP). Despite a number of mutational studies investigating the regulation of ORN development, a majority of the transcriptional programs that lead to the different ORN classes in the developing olfactory system are unknown. Here we use transcriptional profiling across the time series of antennal development to identify novel transcriptional programs governing the differentiation of ORNs. We surveyed four critical developmental stages of the olfactory system: 3rd instar larval (prepatterning), 8 hours after puparium formation (APF, SOP selection), 40 hrs APF (neurogenesis), and adult antennae. We focused on the expression profiles of olfactory receptor genes and transcription factors—the two main classes of genes that regulate the sensory identity of ORNs. We identify distinct clusters of genes that have overlapping temporal expression profiles suggesting they have a key role during olfactory system development. We show that the expression of the transcription factor distal antenna (dan) is highly similar to other prepatterning factors and is required for the expression of a subset of ORs. PMID:28102318

  15. Identification of Putative Olfactory Genes from the Oriental Fruit Moth Grapholita molesta via an Antennal Transcriptome Analysis

    PubMed Central

    Li, Yiping; Wu, Junxiang

    2015-01-01

    Background The oriental fruit moth, Grapholita molesta, is an extremely important oligophagous pest species of stone and pome fruits throughout the world. As a host-switching species, adult moths, especially females, depend on olfactory cues to a large extent in locating host plants, finding mates, and selecting oviposition sites. The identification of olfactory genes can facilitate investigation on mechanisms for chemical communications. Methodology/Principal Finding We generated transcriptome of female antennae of G.molesta using the next-generation sequencing technique, and assembled transcripts from RNA-seq reads using Trinity, SOAPdenovo-trans and Abyss-trans assemblers. We identified 124 putative olfactory genes. Among the identified olfactory genes, 118 were novel to this species, including 28 transcripts encoding for odorant binding proteins, 17 chemosensory proteins, 48 odorant receptors, four gustatory receptors, 24 ionotropic receptors, two sensory neuron membrane proteins, and one odor degrading enzyme. The identified genes were further confirmed through semi-quantitative reverse transcription PCR for transcripts coding for 26 OBPs and 17 CSPs. OBP transcripts showed an obvious antenna bias, whereas CSP transcripts were detected in different tissues. Conclusion Antennal transcriptome data derived from the oriental fruit moth constituted an abundant molecular resource for the identification of genes potentially involved in the olfaction process of the species. This study provides a foundation for future research on the molecules involved in olfactory recognition of this insect pest, and in particular, the feasibility of using semiochemicals to control this pest. PMID:26540284

  16. 17β-estradiol enhances memory duration in the main olfactory bulb in CD-1 mice.

    PubMed

    Dillon, T Samuel; Fox, Laura C; Han, Crystal; Linster, Christiane

    2013-12-01

    Rodents rely heavily on odor detection, discrimination, and memory to locate food, find mates, care for pups, and avoid predators. Estrogens have been shown to increase memory retention in rodents performing spatial memory and object placement tasks. Here we evaluate the extent to which 17β-estradiol modulates memory formation and duration in the olfactory system. Adult CD-1 mice were gonadectomized and given either systemic 17β-estradiol replacement, local 17β-estradiol in the main olfactory bulb, or no replacement. Before performing the behavioral task the mice were given saline or PHTPP (an estrogen receptor β [ER-β] antagonist) via bilateral infusion into the main olfactory bulb. As the beta-type estrogen receptor (ER-β) is more abundant than the alpha-type estrogen receptor in the murine main olfactory bulb, the current study focuses on 17β-estradiol and its interactions with ERβ. Habituation, a simple, nonassociative learning task in which an animal is exposed to the same odor over successive presentations, was used to evaluate the animals' ability to detect odors and form an olfactory memory. To evaluate memory duration, we added a final trial of intertrial interval time (30 or 60 min) in which we presented the habituated odor. Neither surgical nor drug manipulation affected the ability of mice to detect or habituate to an odor. After habituation, gonadectomized 17β-estradiol-treated mice retained memory of an odor for 30 min, whereas non-estradiol-treated, 17β-estradiol+ERβ antagonist (PHTPP), and untreated male mice did not remember an odor 30 min after habituation. The results show that both systemic and local bulbar infusions of 17β-estradiol enhance odor memory duration in mice.

  17. Compensatory responses to age-related decline in odor quality acuity: cholinergic neuromodulation and olfactory enrichment.

    PubMed

    Mandairon, Nathalie; Peace, Shane T; Boudadi, Karim; Boxhorn, Christine E; Narla, Venkata Anupama; Suffis, Sara D; Cleland, Thomas A

    2011-12-01

    The perceptual differentiation of odors can be measured behaviorally using generalization gradients. The steepness of these gradients defines a form of olfactory acuity for odor quality that depends on neural circuitry within the olfactory bulb and is regulated by cholinergic activity therein as well as by associative learning. Using this system as a reduced model for age-related cognitive decline, we show that aged mice, while maintaining almost the same baseline behavioral performance as younger mice, are insensitive to the effects of acutely elevated acetylcholine, which sharpens generalization gradients in young adult mice. Moreover, older mice exhibit evidence of chronically elevated