Science.gov

Sample records for adult human olfactory

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. Mirror Sniffing: Humans Mimic Olfactory Sampling Behavior

    PubMed Central

    2014-01-01

    Ample evidence suggests that social chemosignaling plays a significant role in human behavior. Processing of odors and chemosignals depends on sniffing. Given this, we hypothesized that humans may have evolved an automatic mechanism driving sniffs in response to conspecific sniffing. To test this, we measured sniffing behavior of human subjects watching the movie Perfume, which contains many olfactory sniffing events. Despite the total absence of odor, observers sniffed when characters in the movie sniffed. Moreover, this effect was most pronounced in scenes where subjects heard the sniff but did not see the sniffed-at object. We liken this response to the orienting towards conspecific gaze in vision and argue that its robustness further highlights the significance of olfactory information processing in human behavior. PMID:24457159

  14. Olfactory Orientation and Navigation in Humans

    PubMed Central

    Jacobs, Lucia F.; Arter, Jennifer; Cook, Amy; Sulloway, Frank J.

    2015-01-01

    Although predicted by theory, there is no direct evidence that an animal can define an arbitrary location in space as a coordinate location on an odor grid. Here we show that humans can do so. Using a spatial match-to-sample procedure, humans were led to a random location within a room diffused with two odors. After brief sampling and spatial disorientation, they had to return to this location. Over three conditions, participants had access to different sensory stimuli: olfactory only, visual only, and a final control condition with no olfactory, visual, or auditory stimuli. Humans located the target with higher accuracy in the olfaction-only condition than in the control condition and showed higher accuracy than chance. Thus a mechanism long proposed for the homing pigeon, the ability to define a location on a map constructed from chemical stimuli, may also be a navigational mechanism used by humans. PMID:26083337

  15. 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.

  16. 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.

  17. 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

  18. Olfactory drug effects approached from human-derived data.

    PubMed

    Lötsch, Jörn; Knothe, Claudia; Lippmann, Catharina; Ultsch, Alfred; Hummel, Thomas; Walter, Carmen

    2015-11-01

    The complexity of the sense of smell makes adverse olfactory effects of drugs highly likely, which can impact a patient's quality of life. Here, we present a bioinformatics approach that identifies drugs with potential olfactory effects by connecting drug target expression patterns in human olfactory tissue with drug-related information and the underlying molecular drug targets taken from publically available databases. We identified 71 drugs with listed olfactory effects and 147 different targets. Taking the target-based approach further, we found additional drugs with potential olfactory effects, including 152 different substances interacting with genes expressed in the human olfactory bulb. Our proposed bioinformatics approach provides plausible hypotheses about mechanistic drug effects for drug discovery and repurposing and, thus, would be appropriate for use during drug development.

  19. 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

  20. 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.

  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. 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.

  3. 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

  4. 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.

  5. Olfactory perception, cognition, and dysfunction in humans.

    PubMed

    Stevenson, Richard J

    2013-05-01

    The main functions of olfaction relate to finding food, avoiding predators and disease, and social communication. Its role in detecting food has resulted in a unique dual mode sensory system. Environmental odorants are 'smelled' via the external nostrils, while volatile chemicals in food-detected by the same receptors-arrive via the nasopharynx, contributing to flavor. This arrangement allows the brain to link the consequences of eating with a food's odor, and then later to use this information in the search for food. Recognizing an odorant-a food, mate, or predator-requires the detection of complex chemical blends against a noisy chemical background. The brain solves this problem in two ways. First, by rapid adaptation to background odorants so that new odorants stand out. Second, by pattern matching the neural representation of an odorant to prior olfactory experiences. This account is consistent with olfactory sensory physiology, anatomy, and psychology. Odor perception, and its products, may be subject to further processing-olfactory cognition. While olfactory cognition has features in common with visual or auditory cognition, several aspects are unique, and even those that are common may be instantiated in different ways. These differences can be productively used to evaluate the generality of models of cognition and consciousness. Finally, the olfactory system can breakdown, and this may be predictive of the onset of neurodegenerative conditions such as Alzheimer's, as well as having prognostic value in other disorders such as schizophrenia. WIREs Cogn Sci 2013, 4:273-284. doi: 10.1002/wcs.1224 For further resources related to this article, please visit the WIREs website.

  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. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  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. 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. 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

  19. 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.

  20. 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

  1. 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

  2. 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

  3. Characterization of the Olfactory Receptors Expressed in Human Spermatozoa

    PubMed Central

    Flegel, Caroline; Vogel, Felix; Hofreuter, Adrian; Schreiner, Benjamin S. P.; Osthold, Sandra; Veitinger, Sophie; Becker, Christian; Brockmeyer, Norbert H.; Muschol, Michael; Wennemuth, Gunther; Altmüller, Janine; Hatt, Hanns; Gisselmann, Günter

    2016-01-01

    The detection of external cues is fundamental for human spermatozoa to locate the oocyte in the female reproductive tract. This task requires a specific chemoreceptor repertoire that is expressed on the surface of human spermatozoa, which is not fully identified to date. Olfactory receptors (ORs) are candidate molecules and have been attributed to be involved in sperm chemotaxis and chemokinesis, indicating an important role in mammalian spermatozoa. An increasing importance has been suggested for spermatozoal RNA, which led us to investigate the expression of all 387 OR genes. This study provides the first comprehensive analysis of OR transcripts in human spermatozoa of several individuals by RNA-Seq. We detected 91 different transcripts in the spermatozoa samples that could be aligned to annotated OR genes. Using stranded mRNA-Seq, we detected a class of these putative OR transcripts in an antisense orientation, indicating a different function, rather than coding for a functional OR protein. Nevertheless, we were able to detect OR proteins in various compartments of human spermatozoa, indicating distinct functions in human sperm. A panel of various OR ligands induced Ca2+ signals in human spermatozoa, which could be inhibited by mibefradil. This study indicates that a variety of ORs are expressed at the mRNA and protein level in human spermatozoa. PMID:26779489

  4. 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

  5. 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

  6. 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

  7. 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.

  8. Age-associated loss of selectivity in human olfactory sensory neurons.

    PubMed

    Rawson, Nancy E; Gomez, George; Cowart, Beverly J; Kriete, Andres; Pribitkin, Edmund; Restrepo, Diego

    2012-09-01

    We report a cross-sectional study of olfactory impairment with age based on both odorant-stimulated responses of human olfactory sensory neurons (OSNs) and tests of olfactory threshold sensitivity. A total of 621 OSNs from 440 subjects in 2 age groups of younger (≤ 45 years) and older (≥ 60 years) subjects were investigated using fluorescence intensity ratio fura-2 imaging. OSNs were tested for responses to 2 odorant mixtures, as well as to subsets of and individual odors in those mixtures. Whereas cells from younger donors were highly selective in the odorants to which they responded, cells from older donors were more likely to respond to multiple odor stimuli, despite a loss in these subjects' absolute olfactory sensitivity, suggesting a loss of specificity. This degradation in peripheral cellular specificity may impact odor discrimination and olfactory adaptation in the elderly. It is also possible that chronic adaptation as a result of reduced specificity contributes to observed declines in absolute sensitivity.

  9. 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

  10. Surface coatings of ZnO nanoparticles mitigate differentially a host of transcriptional, protein and signalling responses in primary human olfactory cells

    PubMed Central

    2013-01-01

    Background Inhaled nanoparticles have been reported in some instances to translocate from the nostril to the olfactory bulb in exposed rats. In close proximity to the olfactory bulb is the olfactory mucosa, within which resides a niche of multipotent cells. Cells isolated from this area may provide a relevant in vitro system to investigate potential effects of workplace exposure to inhaled zinc oxide nanoparticles. Methods Four types of commercially-available zinc oxide (ZnO) nanoparticles, two coated and two uncoated, were examined for their effects on primary human cells cultured from the olfactory mucosa. Human olfactory neurosphere-derived (hONS) cells from healthy adult donors were analyzed for modulation of cytokine levels, activation of intracellular signalling pathways, changes in gene-expression patterns across the whole genome, and compromised cellular function over a 24 h period following exposure to the nanoparticles suspended in cell culture medium. Results ZnO nanoparticle toxicity in hONS cells was mediated through a battery of mechanisms largely related to cell stress, inflammatory response and apoptosis, but not activation of mechanisms that repair damaged DNA. Surface coatings on the ZnO nanoparticles mitigated these cellular responses to varying degrees. Conclusions The results indicate that care should be taken in the workplace to minimize generation of, and exposure to, aerosols of uncoated ZnO nanoparticles, given the adverse responses reported here using multipotent cells derived from the olfactory mucosa. PMID:24144420

  11. The importance of the olfactory sense in the human behavior and evolution

    PubMed Central

    Mella, C; Georgescu, M; Perederco, C

    2009-01-01

    Not long ago it was believed that the human olfactory sense had a low importance, a vision which turned into the exploration of the environment. Recent studies have shown that, despite the weak representation of the olfactory receptor common in other species too, the cortical areas of integration of the olfactory sensations are very large and have important interconnections with memory, language, and neuro–vegetative areas. In humans, olfaction has a small contribution in identifying objects or other people, but plays an important social and emotional part. People learn to love or to hate certain foods or objects only by appreciating their odor and this proved to be a very important economic factor. The most significant role of olfactory signals in humans appears to be the modulation of their behavior and interpersonal relationships, of their affiliation to certain groups or social classes, having a major influence in their tastes and personality. PMID:20108540

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. The dynamics of adult neurogenesis in human hippocampus

    PubMed Central

    Ihunwo, Amadi O.; Tembo, Lackson H.; Dzamalala, Charles

    2016-01-01

    The phenomenon of adult neurogenesis is now an accepted occurrence in mammals and also in humans. At least two discrete places house stem cells for generation of neurons in adult brain. These are olfactory system and the hippocampus. In animals, newly generated neurons have been directly or indirectly demonstrated to generate a significant amount of new neurons to have a functional role. However, the data in humans on the extent of this process is still scanty and such as difficult to comprehend its functional role in humans. This paper explores the available data on as extent of adult hippocampal neurogenesis in humans and makes comparison to animal data. PMID:28197172

  17. Olfactory Dysfunctions and Decreased Nitric Oxide Production in the Brain of Human P301L Tau Transgenic Mice.

    PubMed

    Hu, Yang; Ding, Wenting; Zhu, Xiaonan; Chen, Ruzhu; Wang, Xuelan

    2016-04-01

    Different patterns of olfactory dysfunction have been found in both patients and mouse models of Alzheimer's Disease. However, the underlying mechanism of the dysfunction remained unknown. Deficits of nitric oxide production in brain can cause olfactory dysfunction by preventing the formation of olfactory memory. The aim of this study was to investigate the behavioral changes in olfaction and alterations in metabolites of nitric oxide, nitrate/nitrite concentration, in the brain of human P301L tau transgenic mice. The tau mice showed impairments in olfaction and increased abnormal phosphorylation of Tau protein at AT8 in different brain areas, especially in olfactory bulb. We now report that these olfactory deficits and Tau pathological changes were accompanied by decreased nitrate/nitrite concentration in the brain, especially in the olfactory bulb, and reduced expression of nNOS in the brain of tau mice. These findings provided evidence of olfactory dysfunctions correlated with decreased nitric oxide production in the brain of tau mice.

  18. 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.

  19. 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.

  20. Human olfactory bulb neural stem cells expressing hNGF restore cognitive deficit in Alzheimer's disease rat model.

    PubMed

    Marei, Hany E S; Farag, Amany; Althani, Asma; Afifi, Nahla; Abd-Elmaksoud, Ahmed; Lashen, Samah; Rezk, Shaymaa; Pallini, Roberto; Casalbore, Patrizia; Cenciarelli, Carlo

    2015-01-01

    In this study, we aim to demonstrate the fate of allogenic adult human olfactory bulb neural stem/progenitor cells (OBNSC/NPCs) transplanted into the rat hippocampus treated with ibotenic acid (IBO), a neurotoxicant specific to hippocampal cholinergic neurons that are lost in Alzheimer's disease. We assessed their possible ability to survive, integrate, proliferate, and differentiate into different neuronal and glial elements: we also evaluate their possible therapeutic potential, and the mechanism(s) relevant to neuroprotection following their engraftment into the CNS milieu. OBNSC/NPCs were isolated from adult human olfactory bulb patients, genetically engineered to express GFP and human nerve growth factor (hNGF) by lentivirus-mediated infection, and stereotaxically transplanted into the hippocampus of IBO-treated animals and controls. Stereological analysis of engrafted OBNSCs eight weeks post transplantation revealed a 1.89 fold increase with respect to the initial cell population, indicating a marked ability for survival and proliferation. In addition, 54.71 ± 11.38%, 30.18 ± 6.00%, and 15.09 ± 5.38% of engrafted OBNSCs were identified by morphological criteria suggestive of mature neurons, oligodendrocytes and astrocytes respectively. Taken together, this work demonstrated that human OBNSCs expressing NGF ameliorate the cognitive deficiencies associated with IBO-induced lesions in AD model rats, and the improvement can probably be attributed primarily to neuronal and glial cell replacement as well as the trophic influence exerted by the secreted NGF.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. Disinhibition of olfaction: human olfactory performance improves following low levels of alcohol.

    PubMed

    Endevelt-Shapira, Yaara; Shushan, Sagit; Roth, Yehudah; Sobel, Noam

    2014-10-01

    We hypothesize that true human olfactory abilities are obscured by cortical inhibition. Alcohol reduces inhibition. We therefore tested the hypothesis that olfactory abilities will improve following alcohol consumption. We measured olfaction in 85 subjects, 45 in a between-subjects design, and 40 in a repeated-measures within-subjects design before and after consumption of alcoholic or non-alcoholic beverages. Subjects were also assessed using neurocognitive measures of inhibition. Following alcohol consumption, blood alcohol levels ranged from 0.005% to 0.11%. Across subjects, before any consumption of alcohol, we found that individuals who were less inhibited had lower (better) olfactory detection thresholds (r=0.68, p<0.005). Moreover, after alcohol consumption, subjects with low alcohol levels could make olfactory discriminations that subjects with 0% alcohol could not make (chance=33%, alcohol=51.3±22.7%, control=34.7±31.6%, t(43)=2.03, p<0.05). Within subjects, we found correlations between levels of alcohol and olfactory detection (r=0.63, p<0.005) and discrimination (r=-0.50, p<0.05), such that performance was improved at low levels of alcohol (significantly better than baseline for detection) and deteriorated at higher levels of alcohol. Finally, levels of alcohol-induced improved olfactory discrimination were correlated with levels of alcohol-induced cognitive disinhibition (r=0.48, p<0.05). Although we cannot rule out alternative non-inhibitory alcohol-induced routes of influence, we conclude that improved olfaction at low levels of alcohol supports the notion of an inhibitory mechanism obscuring true olfactory abilities.

  8. Pheromone signal transduction in humans: what can be learned from olfactory loss.

    PubMed

    Savic, Ivanka; Hedén-Blomqvist, Ebba; Berglund, Hans

    2009-09-01

    Because humans seem to lack neuronal elements in the vomeronasal organ (VNO), many scientists believe that humans are unable to detect pheromones. This view is challenged by the observations that pheromone-like compounds, 4,16-androstadien-3-one (AND) and oestra-1,3,5(10),16-tetraen-3-ol (EST), activate the human hypothalamus. Whether these activations are mediated via VNO, venous blood or olfactory mucosa is presently unknown. To disentangle between the three alternatives, we conducted activation studies in 12 heterosexual males with chronic anosmia because of nasal polyps. Polyposis hampers signal transduction via the olfactory mucosa without interfering with the VNO or the pheromone transport via venous blood. Twelve healthy men served as controls. Subjects were investigated with (15)O-H(2)O PET during smelling of odorless air (base line), AND, EST, vanillin, and acetone. Smelling of EST activated the anterior hypothalamus in controls, but not anosmics. Neither did the anosmics display cerebral activations with AND or vanillin. Clusters were detected only with the trigeminal odorant acetone, and only in the thalamus, brainstem, the anterior cingulate, and parts of the sensorimotor cortex. Direct comparisons with controls (controls-anosmics) showed clusters in the olfactory cortex (amygdala and piriform cortex) with AND, vanillin, and acetone, and in the anterior hypothalamus with EST. The observed absence of olfactory and presence of trigeminal activations in anosmics indicates that polyposis primarily affected signal processing via the olfactory mucosa. The anosmics inability to activate the hypothalamus with EST, therefore, suggests that in healthy men EST signals were primarily transmitted via the olfactory system.

  9. The human olfactory receptor 17-40: requisites for fitting into the binding pocket.

    PubMed

    Anselmi, Cecilia; Buonocore, Anna; Centini, Marisanna; Facino, Roberto Maffei; Hatt, Hanns

    2011-06-01

    To gain structural insight on the interactions between odorants and the human olfactory receptor, we did homology modelling of the receptor structure, followed by molecular docking simulation with ligands. Molecular dynamics simulation on the structures resulting from docking served to estimate the binding free energy of the various odorant families. A correlation with the odorous properties of the ligands is proposed. We also investigated which residues were involved in the binding of a set of properly synthesised ligands and which were required for fitting inside the binding pocket. Olfactive stimulation of the olfactory receptor with odorous molecules was also investigated, using calcium imaging or electrophysiological recordings.

  10. 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

  11. 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.

  12. 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.

  13. 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…

  14. 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.

  15. 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

  16. Olfactory Sensitivity for Six Predator Odorants in CD-1 Mice, Human Subjects, and Spider Monkeys

    PubMed Central

    Sarrafchi, Amir; Odhammer, Anna M. E.; Hernandez Salazar, Laura Teresa; Laska, Matthias

    2013-01-01

    Using a conditioning paradigm, we assessed the olfactory sensitivity of six CD-1 mice (Mus musculus) for six sulfur-containing odorants known to be components of the odors of natural predators of the mouse. With all six odorants, the mice discriminated concentrations <0.1 ppm (parts per million) from the solvent, and with five of the six odorants the best-scoring animals were even able to detect concentrations <1 ppt (parts per trillion). Four female spider monkeys (Ateles geoffroyi) and twelve human subjects (Homo sapiens) tested in parallel were found to detect the same six odorants at concentrations <0.01 ppm, and with four of the six odorants the best-scoring animals and subjects even detected concentrations <10 ppt. With all three species, the threshold values obtained here are generally lower than (or in the lower range of) those reported for other chemical classes tested previously, suggesting that sulfur-containing odorants may play a special role in olfaction. Across-species comparisons showed that the mice were significantly more sensitive than the human subjects and the spider monkeys with four of the six predator odorants. However, the human subjects were significantly more sensitive than the mice with the remaining two odorants. Human subjects and spider monkeys significantly differed in their sensitivity with only two of the six odorants. These comparisons lend further support to the notion that the number of functional olfactory receptor genes or the relative or absolute size of the olfactory bulbs are poor predictors of a species’ olfactory sensitivity. Analysis of odor structure–activity relationships showed that in both mice and human subjects the type of alkyl rest attached to a thietane and the type of oxygen moiety attached to a thiol significantly affected olfactory sensitivity. PMID:24278296

  17. 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

  18. 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.

  19. 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.

  20. A portable experimental apparatus for human olfactory fMRI experiments.

    PubMed

    Sezille, C; Messaoudi, B; Bertrand, A; Joussain, P; Thévenet, M; Bensafi, M

    2013-08-15

    Human olfactory perception can be measured using psychophysical tools or more complex odor generating devices systems, namely olfactometers. The present paper is aimed at presenting a new inexpensive, non-voluminous portable olfactometer adapted for human fMRI experiments. The system adjusts odorant stimulus presentation to human nasal respiration and records behavioral responses in the same experimental device. Validation by psychophysical measures and photo-ionization detection showed a linear increase in both odor intensity perception and vapor concentration as a function of odorant concentration. Further validation by brain imaging revealed neural activation in typical olfactory areas. In summary, the system represents a new low-cost, easy-use, easy-maintenance portable olfactometry tool for brain imaging, opening up new possibilities for investigating neural response to odors using event-related fMRI designs.

  1. 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.

  2. 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.'

  3. 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.

  4. 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

  5. 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.

  6. Sexual Dimorphism in the Human Olfactory Bulb: Females Have More Neurons and Glial Cells than Males

    PubMed Central

    Oliveira-Pinto, Ana V.; Santos, Raquel M.; Coutinho, Renan A.; Oliveira, Lays M.; Santos, Gláucia B.; Alho, Ana T. L.; Leite, Renata E. P.; Farfel, José M.; Suemoto, Claudia K.; Grinberg, Lea T.; Pasqualucci, Carlos A.; Jacob-Filho, Wilson; Lent, Roberto

    2014-01-01

    Sex differences in the human olfactory function reportedly exist for olfactory sensitivity, odorant identification and memory, and tasks in which odors are rated based on psychological features such as familiarity, intensity, pleasantness, and others. Which might be the neural bases for these behavioral differences? The number of cells in olfactory regions, and especially the number of neurons, may represent a more accurate indicator of the neural machinery than volume or weight, but besides gross volume measures of the human olfactory bulb, no systematic study of sex differences in the absolute number of cells has yet been undertaken. In this work, we investigate a possible sexual dimorphism in the olfactory bulb, by quantifying postmortem material from 7 men and 11 women (ages 55–94 years) with the isotropic fractionator, an unbiased and accurate method to estimate absolute cell numbers in brain regions. Female bulbs weighed 0.132 g in average, while male bulbs weighed 0.137 g, a non-significant difference; however, the total number of cells was 16.2 million in females, and 9.2 million in males, a significant difference of 43.2%. The number of neurons in females reached 6.9 million, being no more than 3.5 million in males, a difference of 49.3%. The number of non-neuronal cells also proved higher in women than in men: 9.3 million and 5.7 million, respectively, a significant difference of 38.7%. The same differences remained when corrected for mass. Results demonstrate a sex-related difference in the absolute number of total, neuronal and non-neuronal cells, favoring women by 40–50%. It is conceivable that these differences in quantitative cellularity may have functional impact, albeit difficult to infer how exactly this would be, without knowing the specific circuits cells make. However, the reported advantage of women as compared to men may stimulate future work on sex dimorphism of synaptic microcircuitry in the olfactory bulb. PMID:25372872

  7. 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.

  8. 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.

  9. 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).

  10. Positive selection moments identify potential functional residues in human olfactory receptors

    NASA Technical Reports Server (NTRS)

    Singer, M. S.; Weisinger-Lewin, Y.; Lancet, D.; Shepherd, G. M.

    1996-01-01

    Correlated mutation analysis and molecular models of olfactory receptors have provided evidence that residues in the transmembrane domains form a binding pocket for odor ligands. As an independent test of these results, we have calculated positive selection moments for the alpha-helical sixth transmembrane domain (TM6) of human olfactory receptors. The moments can be used to identify residues that have been preferentially affected by positive selection and are thus likely to interact with odor ligands. The results suggest that residue 622, which is commonly a serine or threonine, could form critical H-bonds. In some receptors a dual-serine subsite, formed by residues 622 and 625, could bind hydroxyl determinants on odor ligands. The potential importance of these residues is further supported by site-directed mutagenesis in the beta-adrenergic receptor. The findings should be of practical value for future physiological studies, binding assays, and site-directed mutagenesis.

  11. Human metapneumovirus in adults.

    PubMed

    Haas, Lenneke E M; Thijsen, Steven F T; van Elden, Leontine; Heemstra, Karen A

    2013-01-08

    Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children are infected by HMPV below the age of five; the repeated infections throughout life indicate transient immunity. HMPV infections usually are mild and self-limiting, but in the frail elderly and the immunocompromised patients, the clinical course can be complicated. Since culturing the virus is relatively difficult, diagnosis is mostly based on a nucleic acid amplification test, such as reverse transcriptase polymerase chain reaction. To date, no vaccine is available and treatment is supportive. However, ongoing research shows encouraging results. The aim of this paper is to review the current literature concerning HMPV infections in adults, and discuss recent development in treatment and vaccination.

  12. Human Metapneumovirus in Adults

    PubMed Central

    Haas, Lenneke E. M.; Thijsen, Steven F. T.; van Elden, Leontine; Heemstra, Karen A.

    2013-01-01

    Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children are infected by HMPV below the age of five; the repeated infections throughout life indicate transient immunity. HMPV infections usually are mild and self-limiting, but in the frail elderly and the immunocompromised patients, the clinical course can be complicated. Since culturing the virus is relatively difficult, diagnosis is mostly based on a nucleic acid amplification test, such as reverse transcriptase polymerase chain reaction. To date, no vaccine is available and treatment is supportive. However, ongoing research shows encouraging results. The aim of this paper is to review the current literature concerning HMPV infections in adults, and discuss recent development in treatment and vaccination. PMID:23299785

  13. Human Olfactory Mucosa Multipotent Mesenchymal Stromal Cells Promote Survival, Proliferation, and Differentiation of Human Hematopoietic Cells

    PubMed Central

    Diaz-Solano, Dylana; Wittig, Olga; Ayala-Grosso, Carlos; Pieruzzini, Rosalinda

    2012-01-01

    Multipotent mesenchymal stromal cells (MSCs) from the human olfactory mucosa (OM) are cells that have been proposed as a niche for neural progenitors. OM-MSCs share phenotypic and functional properties with bone marrow (BM) MSCs, which constitute fundamental components of the hematopoietic niche. In this work, we investigated whether human OM-MSCs may promote the survival, proliferation, and differentiation of human hematopoietic stem cells (HSCs). For this purpose, human bone marrow cells (BMCs) were co-cultured with OM-MSCs in the absence of exogenous cytokines. At different intervals, nonadherent cells (NACs) were harvested from BMC/OM-MSC co-cultures, and examined for the expression of blood cell markers by flow cytometry. OM-MSCs supported the survival (cell viability >90%) and proliferation of BMCs, after 54 days of co-culture. At 20 days of co-culture, flow cytometric and microscopic analyses showed a high percentage (73%) of cells expressing the pan-leukocyte marker CD45, and the presence of cells of myeloid origin, including polymorphonuclear leukocytes, monocytes, basophils, eosinophils, erythroid cells, and megakaryocytes. Likewise, T (CD3), B (CD19), and NK (CD56/CD16) cells were detected in the NAC fraction. Colony-forming unit–granulocyte/macrophage (CFU-GM) progenitors and CD34+ cells were found, at 43 days of co-culture. Reverse transcriptase–polymerase chain reaction (RT-PCR) studies showed that OM-MSCs constitutively express early and late-acting hematopoietic cytokines (i.e., stem cell factor [SCF] and granulocyte- macrophage colony-stimulating factor [GM-CSF]). These results constitute the first evidence that OM-MSCs may provide an in vitro microenvironment for HSCs. The capacity of OM-MSCs to support the survival and differentiation of HSCs may be related with the capacity of OM-MSCs to produce hematopoietic cytokines. PMID:22471939

  14. Olfactory Mucosa Autografts in Human Spinal Cord Injury: A Pilot Clinical Study

    PubMed Central

    Lima, Carlos; Pratas-Vital, José; Escada, Pedro; Hasse-Ferreira, Armando; Capucho, Clara; Peduzzi, Jean D

    2006-01-01

    Background/Objective: Olfactory mucosa is a readily accessible source of olfactory ensheathing and stem-like progenitor cells for neural repair. To determine the safety and feasibility of transplanting olfactory mucosa autografts into patients with traumatically injured spinal cords, a human pilot clinical study was conducted. Methods: Seven patients ranging from 18 to 32 years of age (American Spinal Injury Association [ASIA] class A) were treated at 6 months to 6.5 years after injury. Olfactory mucosa autografts were transplanted into lesions ranging from 1 to 6 cm that were present at C4–T6 neurological levels. Operations were performed from July 2001 through March 2003. Magnetic resonance imaging (MRI), electromyography (EMG), and ASIA neurological and otolaryngological evaluations were performed before and after surgery. Results: MRI studies revealed moderate to complete filling of the lesion sites. Two patients reported return of sensation in their bladders, and one of these patients regained voluntary contraction of anal sphincter. Two of the 7 ASIA A patients became ASIA C. Every patient had improvement in ASIA motor scores. The mean increase for the 3 subjects with tetraplegia in the upper extremities was 6.3 ± 1.2 (SEM), and the mean increase for the 4 subjects with paraplegia in the lower extremities was 3.9 ± 1.0. Among the patients who improved in their ASIA sensory neurological scores (all except one patient), the mean increase was 20.3 ± 5.0 for light touch and 19.7 ± 4.6 for pinprick. Most of the recovered sensation below the initial level of injury was impaired. Adverse events included sensory decrease in one patient that was most likely caused by difficulty in locating the lesion, and there were a few instances of transient pain that was relieved by medication. EMG revealed motor unit potential when the patient was asked to perform movement. Conclusion: This study shows that olfactory mucosa autograft transplantation into the human injured

  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. Underlying mathematics in diversification of human olfactory receptors in different loci.

    PubMed

    Hassan, Sk Sarif; Choudhury, Pabitra Pal; Goswami, Arunava

    2013-12-01

    As per conservative estimate, approximately 51-105 Olfactory Receptors (ORs) loci are present in human genome occurring in clusters. These clusters are apparently unevenly spread as mosaics over 21 pairs of human chromosomes. Olfactory Receptor (OR) gene families which are thought to have expanded for the need to provide recognition capability for a huge number of pure and complex odorants, form the largest known multigene family in the human genome. Recent studies have shown that 388 full length and 414 OR pseudo-genes are present in these OR genomic clusters. In this paper, the authors report a classification method for all human ORs based on their sequential quantitative information like presence of poly strings of nucleotides bases, long range correlation and so on. An L-System generated sequence has been taken as an input into a star-model of specific subfamily members and resultant sequence has been mapped to a specific OR based on the classification scheme using fractal parameters like Hurst exponent and fractal dimensions.

  17. 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.

  18. 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

  19. Mutations in olfactory signal transduction genes are not a major cause of human congenital general anosmia.

    PubMed

    Feldmesser, Ester; Bercovich, Dani; Avidan, Nili; Halbertal, Shmuel; Haim, Liora; Gross-Isseroff, Ruth; Goshen, Sivan; Lancet, Doron

    2007-01-01

    Anosmia affects the western world population, mostly the elderly, reaching to 5% in subjects over the age of 45 years and strongly lowering their quality of life. A smaller minority (about 0.01%) is born without a sense of smell, afflicted with congenital general anosmia (CGA). No causative genes for human CGA have been identified yet, except for some syndromic cases such as Kallman syndrome. In mice, however, deletion of any of the 3 main olfactory transduction components (guanidine triphosphate binding protein, adenylyl cyclase, and the cyclic adenosine monophosphate-gated channel) causes profound reduction of physiological responses to odorants. In an attempt to identify human CGA-related mutations, we performed whole-genome linkage analysis in affected families, but no significant linkage signals were observed, probably due to the small size of families analyzed. We further carried out direct mutation screening in the 3 main olfactory transduction genes in 64 unrelated anosmic individuals. No potentially causative mutations were identified, indicating that transduction gene variations underlie human CGA rarely and that mutations in other genes have to be identified. The screened genes were found to be under purifying selection, suggesting that they play a crucial functional role not only in olfaction but also potentially in additional pathways.

  20. alpha-Synucleinopathy in the human olfactory system in Parkinson's disease: involvement of calcium-binding protein- and substance P-positive cells.

    PubMed

    Ubeda-Bañon, Isabel; Saiz-Sanchez, Daniel; de la Rosa-Prieto, Carlos; Argandoña-Palacios, Lucia; Garcia-Muñozguren, Susana; Martinez-Marcos, Alino

    2010-06-01

    Hyposmia is an early symptom of idiopathic Parkinson's disease but the pathological bases of such dysfunction are largely unknown. The distribution of alpha-synuclein, which forms Lewy bodies and Lewy neurites, and the types of neurons (based on their neurotransmitters) affected by alpha-synucleinopathy were investigated in the olfactory system in Parkinson's disease. Immunohistochemical distribution of alpha-synuclein and its co-localization with tyrosine hydroxylase, somatostatin, calbindin, calretinin, parvalbumin and substance P in the olfactory bulb, anterior olfactory nucleus, olfactory tubercle and piriform, periamygdaloid and rostral entorhinal cortices of idiopathic Parkinson's disease cases (n = 11) and age-matched controls (n = 11) were investigated. Lewy bodies and Lewy neurites were present in the olfactory bulb, particularly in mitral cells and in the inner plexiform layer. alpha-synuclein was particularly abundant in the different divisions of the anterior olfactory nucleus (bulbar, intrapeduncular, retrobulbar and cortical). In contrast, Lewy bodies and Lewy neurites were less abundant in the olfactory tubercle and olfactory cortices. In the olfactory bulb, anterior olfactory nucleus and olfactory cortices, cells affected by alpha-synucleinopathy rarely co-localized tyrosine hydroxylase or somatostatin, but they frequently co-localized calbindin, calretinin, parvalbumin and substance P. The present data provide evidence that alpha-synucleinopathy affects neurons along the olfactory pathway. Dopamine- and somatostatin-positive cells are rarely affected; whereas the cell types most vulnerable to neurodegeneration include glutamate- (mitral cells), calcium-binding protein- and substance P-positive cells. These results provide data on the distribution and cell types involved by alpha-synucleinopathy in the human olfactory system during Parkinson disease that may be useful for future clinical investigation.

  1. 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…

  2. 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.

  3. 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

  4. Characterization of non-olfactory GPCRs in human sperm with a focus on GPR18

    PubMed Central

    Flegel, Caroline; Vogel, Felix; Hofreuter, Adrian; Wojcik, Sebastian; Schoeder, Clara; Kieć-Kononowicz, Katarzyna; Brockmeyer, Norbert H.; Müller, Christa E.; Becker, Christian; Altmüller, Janine; Hatt, Hanns; Gisselmann, Günter

    2016-01-01

    G protein-coupled receptors (GPCRs) transduce external chemical cues into intracellular signals and are involved in a plethora of physiological processes, but knowledge regarding the function of these receptors in spermatozoa is limited. In the present study, we performed RNA-Seq and analyzed the expression of the all GPCRs except olfactory receptors in human spermatozoa. We revealed the expression of up to 223 different GPCR transcripts in human spermatozoa (FPKM > 0.1) and identified GPR18, a newly described cannabinoid receptor, together with GPR137 and GPR135, as one of the three most highly expressed GPCRs. To date, the expression of GPR18 was completely unknown in human spermatozoa. We confirmed GPR18 expression using RT-PCR and immuncytochemistry experiments and localized the GPR18 protein in the midpiece of human spermatozoa. Stimulation of human spermatozoa with the GPR18 ligand N-arachidonoylglycine induced the phosphorylation of 12 protein kinases, some of them are for example known to be involved in the acrosome reaction. In line with this, N-arachidonoylglycine affected the cytoskeleton by changing levels of F-actin and inducing the acrosome reaction in human spermatozoa in a concentration-dependent manner. Our results indicate that GPR18 might be involved in physiological processes of human spermatozoa, suggesting GPR18 to be a potential player in sperm physiology. PMID:27572937

  5. Structural and Ultrastructural Alterations in Human Olfactory Pathways and Possible Associations with Herpesvirus 6 Infection

    PubMed Central

    Skuja, Sandra; Zieda, Anete; Ravina, Kristine; Chapenko, Svetlana; Roga, Silvija; Teteris, Ojars; Groma, Valerija; Murovska, Modra

    2017-01-01

    Structural and ultrastructural alterations in human olfactory pathways and putative associations with human herpesvirus 6 (HHV-6) infection were studied. The olfactory bulb/tract samples from 20 subjects with an unspecified encephalopathy determined by pathomorphological examination of the brain autopsy, 17 healthy age-matched and 16 younger controls were used. HHV-6 DNA was detected in 60, 29, and 19% of cases in these groups, respectively. In the whole encephalopathy group, significantly more HHV-6 positive neurons and oligodendrocytes were found in the gray matter, whereas, significantly more HHV-6 positive astrocytes, oligodendrocytes, microglia/macrophages and endothelial cells were found in the white matter. Additionally, significantly more HHV-6 positive astrocytes and, in particular, oligodendrocytes were found in the white matter when compared to the gray matter. Furthermore, when only HHV-6 PCR+ encephalopathy cases were studied, we observed similar but stronger associations between HHV-6 positive oligodendrocytes and CD68 positive cells in the white matter. Cellular alterations were additionally evidenced by anti-S100 immunostaining, demonstrating a significantly higher number of S100 positive cells in the gray matter of the whole encephalopathy group when compared to the young controls, and in the white matter when compared to both control groups. In spite the decreased S100 expression in the PCR+ encephalopathy group when compared to PCR- cases and controls, groups demonstrated significantly higher number of S100 positive cells in the white compared to the gray matter. Ultrastructural changes confirming the damage of myelin included irregularity of membranes and ballooning of paranodal loops. This study shows that among the cellular targets of the nervous system, HHV-6 most severely affects oligodendrocytes and the myelin made by them. PMID:28072884

  6. 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.

  7. Arts & Humanities in Adult Education.

    ERIC Educational Resources Information Center

    Word's Worth: A Quarterly Newsletter of the Lifelong Learning Network, 1998

    1998-01-01

    This issue of a quarterly newsletter on lifelong learning focuses on the theme of the arts and humanities in adult literacy education. The following articles are included: (1) "In Defense of a Practical Education" (Earl Shorris); (2) "From the Program Director" (Elizabeth Bryant McCrary); (3) "Vermont Council on the Humanities: Book Discussion…

  8. [Development of the Human Olfactory Bulbs in the Prenatal Ontogenesis: an Immunochistochemical Study with Markers of Presynaptic Terminals (anti-SNAP-25, -Synapsin-I, -Synaptophysin)].

    PubMed

    Kharlamova, A S; Barabanov, V M; Saveliev, S V

    2015-01-01

    We provide the data of the olfactory bulbs (OB) development in the human fetuses on the stages from 8 week to birth. Immunochistochemical markers of presynaptic terminals (anti-SNAP-25, -synapsin-I, -synaptophysin) were used to evaluate the maturation of the OB. Differentiation of the OB layers begins from periphery, which implicitly evidences that growth of the olfactory nerves fibers induses not only anatomical differentiation of the OB, but also differentiation of its functional layers. The sites of the developing glomerulus are revealed using the immunochistochemical prosedure on the stage before distinct glomerulus can be identified with common histological procedure. OB conductive system demonstrates immunoreactivity with the antibodies to the presynaptic proteins on the all stages from 10-11 weeks of fetus development. Four stages of the OB development are described. All functional layers of the OB are mature at the 22-weeks stage. Further differentiation of the OB neuroblasts, including lamina formation of the internal granular leyer, glomerular layer development, OB growth continue after 20-22 weeks stage until 38-40 weeks of the fetus develoment. Patterns of the immunoreactivity with antibodies to SNAP-25, synapsin-I and synaptophysin are completely appropriate to those of adult's OB on the 38-40 weeks of the prenatal development. Complete maturity of the human OB is achived at 38-40 weeks of the prenatal development.

  9. 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.

  10. 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

  11. 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

  12. Anatomy and Cellular Constituents of the Human Olfactory Mucosa: A Review

    PubMed Central

    Chen, C. Russell; Kachramanoglou, Carolina; Li, Daqing; Andrews, Peter; Choi, David

    2014-01-01

    Studies using animal models have recently suggested that the olfactory mucosa may be a source of cells capable of stimulating and contributing to complex neurologic regeneration. Several groups have already transplanted cell derivatives from the olfactory mucosa into injury models, and the results so far have been promising. To fully appreciate the meaning of these experiments, a better understanding of the cellular biology and physiology of the olfactory system is necessary. It is therefore of utmost importance for us to first identify and understand its constituents. PMID:25302141

  13. Olfactory Receptors Modulate Physiological Processes in Human Airway Smooth Muscle Cells

    PubMed Central

    Kalbe, Benjamin; Knobloch, Jürgen; Schulz, Viola M.; Wecker, Christine; Schlimm, Marian; Scholz, Paul; Jansen, Fabian; Stoelben, Erich; Philippou, Stathis; Hecker, Erich; Lübbert, Hermann; Koch, Andrea; Hatt, Hanns; Osterloh, Sabrina

    2016-01-01

    Pathophysiological mechanisms in human airway smooth muscle cells (HASMCs) significantly contribute to the progression of chronic inflammatory airway diseases with limited therapeutic options, such as severe asthma and COPD. These abnormalities include the contractility and hyperproduction of inflammatory proteins. To develop therapeutic strategies, key pathological mechanisms, and putative clinical targets need to be identified. In the present study, we demonstrated that the human olfactory receptors (ORs) OR1D2 and OR2AG1 are expressed at the RNA and protein levels in HASMCs. Using fluorometric calcium imaging, specific agonists for OR2AG1 and OR1D2 were identified to trigger transient Ca2+ increases in HASMCs via a cAMP-dependent signal transduction cascade. Furthermore, the activation of OR2AG1 via amyl butyrate inhibited the histamine-induced contraction of HASMCs, whereas the stimulation of OR1D2 with bourgeonal led to an increase in cell contractility. In addition, OR1D2 activation induced the secretion of IL-8 and GM-CSF. Both effects were inhibited by the specific OR1D2 antagonist undecanal. We herein provide the first evidence to show that ORs are functionally expressed in HASMCs and regulate pathophysiological processes. Therefore, ORs might be new therapeutic targets for these diseases, and blocking ORs could be an auspicious strategy for the treatment of early-stage chronic inflammatory lung diseases. PMID:27540365

  14. Partial Conservation between Mice and Humans in Olfactory Bulb Interneuron Transcription Factor Codes.

    PubMed

    Fujiwara, Nana; Cave, John W

    2016-01-01

    The mammalian main olfactory bulb (OB) has a large population of GABAergic inhibitory interneurons that contains several subtypes defined by the co-expression other neurotransmitters and calcium binding proteins. The three most commonly studied OB interneuron subtypes co-express either Calretinin, Calbindin, or Tyrosine hydroxylase (Th). Combinations of transcription factors used to specify the phenotype of progenitors are referred to as transcription factor codes, and the current understanding of transcription factor codes that specify OB inhibitory neuron phenotypes are largely based on studies in mice. The conservation of these transcription factor codes in the human OB, however, has not been investigated. The aim of this study was to establish whether transcription factor codes in OB interneurons are conserved between mice and humans. This study compared the co-expression of Foxp2, Meis2, Pax6, and Sp8 transcription factors with Calretinin, Calbindin, or Th in human and mouse OB interneurons. This analysis found strong conservation of Calretinin co-expression with Sp8 and Meis2 as well as Th co-expression with Pax6 and Meis2. This analysis also showed that selective Foxp2 co-expression with Calbindin was conserved between mice and humans, which suggests Foxp2 is a novel determinant of the OB Calbindin interneuron phenotype. Together, the findings in this study provide insight into the conservation of transcription codes for OB interneuron phenotypes between humans and mice, as well as reveal some important differences between the species. This advance in our understanding of transcription factor codes in OB interneurons provides an important complement to the codes that have been established for other regions within the mammalian central nervous system, such as the cortex and spinal cord.

  15. Partial Conservation between Mice and Humans in Olfactory Bulb Interneuron Transcription Factor Codes

    PubMed Central

    Fujiwara, Nana; Cave, John W.

    2016-01-01

    The mammalian main olfactory bulb (OB) has a large population of GABAergic inhibitory interneurons that contains several subtypes defined by the co-expression other neurotransmitters and calcium binding proteins. The three most commonly studied OB interneuron subtypes co-express either Calretinin, Calbindin, or Tyrosine hydroxylase (Th). Combinations of transcription factors used to specify the phenotype of progenitors are referred to as transcription factor codes, and the current understanding of transcription factor codes that specify OB inhibitory neuron phenotypes are largely based on studies in mice. The conservation of these transcription factor codes in the human OB, however, has not been investigated. The aim of this study was to establish whether transcription factor codes in OB interneurons are conserved between mice and humans. This study compared the co-expression of Foxp2, Meis2, Pax6, and Sp8 transcription factors with Calretinin, Calbindin, or Th in human and mouse OB interneurons. This analysis found strong conservation of Calretinin co-expression with Sp8 and Meis2 as well as Th co-expression with Pax6 and Meis2. This analysis also showed that selective Foxp2 co-expression with Calbindin was conserved between mice and humans, which suggests Foxp2 is a novel determinant of the OB Calbindin interneuron phenotype. Together, the findings in this study provide insight into the conservation of transcription codes for OB interneuron phenotypes between humans and mice, as well as reveal some important differences between the species. This advance in our understanding of transcription factor codes in OB interneurons provides an important complement to the codes that have been established for other regions within the mammalian central nervous system, such as the cortex and spinal cord. PMID:27489533

  16. Dogs'olfactory diagnostics applied on human species: state of the art and clinical perspectives.

    PubMed

    Palmieri, B; Nardo, B; Lippi, G; Palmieri, L; Vadalà, M; Laurino, C

    2016-01-01

    Dogs'smell ability is about 10000-100000 more developed than humans' one. Dogs smell is usually exploited in forensic medicine, to find missing people and specific substances showing peculiar sensorial features. In clinic, there is the possibility to take advantage of dogs smell, which are conveniently trained, for the screening of cancers and other diseases. The common feature is the presence of molecules in organic samples that may be considered as biomarkers of a specific pathology. In cancer, scientific evidences exist about screening of melanoma, lung, breast, rectum, ovarian, prostate and bladder cancer. Instead, other pathologies manifest the presence of organic volatile compounds in biologic materials, such as spit, faeces and urine that may be studied by dogs smell in order to identify the presence of a specific disease. This review shows the state of the art of actual dogs' olfactory ability based on scientific principles and the advantages and the disadvantages of this method. The authors also reveal some potential pathologies joined by the presence of organic volatile compounds, which may be investigated by dogs smell.

  17. Human olfactory consciousness and cognition: its unusual features may not result from unusual functions but from limited neocortical processing resources

    PubMed Central

    Stevenson, Richard J.; Attuquayefio, Tuki

    2013-01-01

    Human and animal olfactory perception is shaped both by functional demands and by various environmental constraints seemingly peculiar to chemical stimuli. These demands and constraints may have generated a sensory system that is cognitively distinct from the major senses. In this article we identify these various functional demands and constraints, and examine whether they can be used to account for olfaction's unique cognitive features on a case-by-case basis. We then use this as grounds to argue that specific conscious processes do have functional value, a finding that naturally emerges when a comparative approach to consciousness across the senses is adopted. More generally, we conclude that certain peculiar features of olfactory cognition may owe more to limited neocortical processing resources, than they do to the challenges faced by perceiving chemical stimuli. PMID:24198808

  18. Human olfactory receptors: recombinant expression in the baculovirus/Sf9 insect cell system, functional characterization, and odorant identification.

    PubMed

    Matarazzo, Valéry; Ronin, Catherine

    2013-01-01

    Cell surface expression of recombinant olfactory receptors (ORs) is a major limitation in characterizing their functional nature. We have shown that the recombinant expression of a human OR, OR 17-210, in the baculovirus/Sf9 insect cell system allows this protein to be expressed at the cell surface. We used Ca(2+) imaging to demonstrate that recombinant OR 17-210 produces cellular activities upon odorant stimulation with ketones. Furthermore, this expression and functional system has been used to show that the preincubation of Human Odorant Binding Protein 2A decrease the calcium response of OR 17-210 following stimulation by acetophenone and beta ionone.

  19. 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.

  20. Characterization of Clustered MHC-Linked Olfactory Receptor Genes in Human and Mouse

    PubMed Central

    Younger, Ruth M.; Amadou, Claire; Bethel, Graeme; Ehlers, Anke; Lindahl, Kirsten Fischer; Forbes, Simon; Horton, Roger; Milne, Sarah; Mungall, Andrew J.; Trowsdale, John; Volz, Armin; Ziegler, Andreas; Beck, Stephan

    2001-01-01

    Olfactory receptor (OR) loci frequently cluster and are present on most human chromosomes. They are members of the seven transmembrane receptor (7-TM) superfamily and, as such, are part of one of the largest mammalian multigene families, with an estimated copy number of up to 1000 ORs per haploid genome. As their name implies, ORs are known to be involved in the perception of odors and possibly also in other, nonolfaction-related, functions. Here, we report the characterization of ORs that are part of the MHC-linked OR clusters in human and mouse (partial sequence only). These clusters are of particular interest because of their possible involvement in olfaction-driven mate selection. In total, we describe 50 novel OR loci (36 human, 14 murine), making the human MHC-linked cluster the largest sequenced OR cluster in any organism so far. Comparative and phylogenetic analyses confirm the cluster to be MHC-linked but divergent in both species and allow the identification of at least one ortholog that will be useful for future regulatory and functional studies. Quantitative feature analysis shows clear evidence of duplications of blocks of OR genes and reveals the entire cluster to have a genomic environment that is very different from its neighboring regions. Based on in silico transcript analysis, we also present evidence of extensive long-distance splicing in the 5′-untranslated regions and, for the first time, of alternative splicing within the single coding exon of ORs. Taken together with our previous finding that ORs are also polymorphic, the presented data indicate that the expression, function, and evolution of these interesting genes might be more complex than previously thought. [The sequence data described in this paper have been submitted to the EMBL nucleotide data library under accession nos. Z84475, Z98744, Z98745, AL021807, AL021808, AL022723, AL022727, AL031893, AL035402, AL035542, AL050328, AL050339, AL078630, AL096770, AL121944, AL133160, and AL

  1. Global Survey of Variation in a Human Olfactory Receptor Gene Reveals Signatures of Non-Neutral Evolution

    PubMed Central

    Gokcumen, Omer; Qureshy, Zoya; Bruguera, Elise; Savangsuksa, Aulaphan; Cobb, Matthew; Matsunami, Hiroaki

    2015-01-01

    Allelic variation at 4 loci in the human olfactory receptor gene OR7D4 is associated with perceptual variation in the sex steroid-derived odorants, androstenone, and androstadienone. Androstadienone has been linked with chemosensory identification whereas androstenone makes pork from uncastrated pigs distasteful (“boar taint”). In a sample of 2224 individuals from 43 populations, we identified 45 OR7D4 single nucleotide polymorphisms. Coalescent modeling of frequency-site-spectrum-based statistics identified significant deviation from neutrality in human OR7D4; individual populations with statistically significant deviations from neutrality include Gujarati, Beijing Han, Great Britain, Iberia, and Puerto Rico. Analysis of molecular variation values indicated statistically significant population differentiation driven mainly by the 4 alleles associated with androstenone perception variation; however, fixation values were low suggesting that genetic structure may not have played a strong role in creating these group divisions. We also studied OR7D4 in the genomes of extinct members of the human lineage: Altai Neandertal and Denisovan. No variants were identified in Altai but 2 were in Denisova, one of which is shared by modern humans and one of which is novel. A functional test of modern human and a synthesized mutant Denisova OR7D4 indicated no statistically significant difference in responses to androstenone between the 2 species. Our results suggest non-neutral evolution for an olfactory receptor gene. PMID:26072518

  2. Early in vivo Effects of the Human Mutant Amyloid-β Protein Precursor (hAβPPSwInd) on the Mouse Olfactory Bulb.

    PubMed

    Rusznák, Zoltán; Kim, Woojin Scott; Hsiao, Jen-Hsiang T; Halliday, Glenda M; Paxinos, George; Fu, YuHong

    2016-01-01

    The amyloid-β protein precursor (AβPP) has long been linked to Alzheimer's disease (AD). Using J20 mice, which express human AβPP with Swedish and Indiana mutations, we studied early pathological changes in the olfactory bulb. The presence of AβPP/amyloid-β (Aβ) was examined in mice aged 3 months (before the onset of hippocampal Aβ deposition) and over 5 months (when hippocampal Aβ deposits are present). The number of neurons, non-neurons, and proliferating cells was assessed using the isotropic fractionator method. Our results demonstrate that although AβPP is overexpressed in some of the mitral cells, widespread Aβ deposition and microglia aggregates are not prevalent in the olfactory bulb. The olfactory bulbs of the younger J20 group harbored significantly fewer neurons than those of the age-matched wild-type mice (5.57±0.13 million versus 6.59±0.36 million neurons; p = 0.011). In contrast, the number of proliferating cells was higher in the young J20 than in the wild-type group (i.e., 6617±425 versus 4455±623 cells; p = 0.011). A significant increase in neurogenic activity was also observed in the younger J20 olfactory bulb. In conclusion, our results indicate that (1) neurons participating in the mouse olfactory function overexpress AβPP; (2) the cellular composition of the young J20 olfactory bulb is different from that of wild-type littermates; (3) these differences may reflect altered neurogenic activity and/or delayed development of the J20 olfactory system; and (4) AβPP/Aβ-associated pathological changes that take place in the J20 hippocampus and olfactory bulb are not identical.

  3. 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.

  4. 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.

  5. 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.

  6. Perceptual blending in odor mixtures depends on the nature of odorants and human olfactory expertise.

    PubMed

    Barkat, S; Le Berre, E; Coureaud, G; Sicard, G; Thomas-Danguin, T

    2012-02-01

    Our olfactory system is confronted with complex mixtures of odorants, often recognized as single entities due to odor blending (e.g., coffee). In contrast, we are also able to discriminate odors from complex mixtures (e.g., off-odors). Therefore, the olfactory system is able to engage either configural or elemental processes when confronted with mixtures. However, the rules that govern the involvement of these processes during odor perception remain poorly understood. In our first experiment, we examined whether simple odorant mixtures (binary/ternary) could elicit configural perception. Twenty untrained subjects were asked to evaluate the odor typicality of mixtures and their constituents. The results revealed a significant increase in odor typicality in some but not all mixtures as compared with the single components, which suggest that perceptual odor blending can occur only in specific mixtures (configural processing). In our second experiment, we tested the hypothesis that general olfactory expertise can improve elemental perception of mixtures. Thirty-two trained subjects evaluated the odor typicality of the stimuli presented during the first experiment, and their responses were compared with those obtained from the untrained panelists. The results support the idea that general training with odors increases the elemental perception of binary and ternary blending mixtures.

  7. 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.

  8. Human olfactory mesenchymal stromal cell transplants promote remyelination and earlier improvement in gait co‐ordination after spinal cord injury

    PubMed Central

    Lindsay, Susan L.; Toft, Andrew; Griffin, Jacob; M. M. Emraja, Ahmed

    2017-01-01

    Autologous cell transplantation is a promising strategy for repair of the injured spinal cord. Here we have studied the repair potential of mesenchymal stromal cells isolated from the human olfactory mucosa after transplantation into a rodent model of incomplete spinal cord injury. Investigation of peripheral type remyelination at the injury site using immunocytochemistry for P0, showed a more extensive distribution in transplanted compared with control animals. In addition to the typical distribution in the dorsal columns (common to all animals), in transplanted animals only, P0 immunolabelling was consistently detected in white matter lateral and ventral to the injury site. Transplanted animals also showed reduced cavitation. Several functional outcome measures including end‐point electrophysiological testing of dorsal column conduction and weekly behavioural testing of BBB, weight bearing and pain, showed no difference between transplanted and control animals. However, gait analysis revealed an earlier recovery of co‐ordination between forelimb and hindlimb stepping in transplanted animals. This improvement in gait may be associated with the enhanced myelination in ventral and lateral white matter, where fibre tracts important for locomotion reside. Autologous transplantation of mesenchymal stromal cells from the olfactory mucosa may therefore be therapeutically beneficial in the treatment of spinal cord injury. GLIA 2017 GLIA 2017;65:639–656 PMID:28144983

  9. An implicit measure of olfactory performance for non-human primates reveals aversive and pleasant odor conditioning.

    PubMed

    Livneh, Uri; Paz, Rony

    2010-09-30

    We have little understanding of how odorants are processed in neural networks of the primate brain. Because chemo-stimuli are harder to control than physical stimuli (e.g. vision, audition), such research was limited by the temporal resolution, accuracy, and reliability of olfactometers (odor producing machines). Recent advances were able to create olfactometers that overcome these limitations, allowing their use together with neuroimaging techniques in humans. From the behavioral point of view, olfaction research requires a behavioral measure that can be used to quantify olfactory performance. This becomes a real problem when working with animals, where, unlike humans, explicit measures are harder to obtain. Furthermore, because odorants are powerful primitive reinforcers, such implicit measures can be beneficial to use in learning paradigms. Here we describe an olfactometer suitable for use in non-human primates, and an end-port design that allows the accurate measure of real-time respiratory modulations that are elicited in response to odor presentation. We demonstrate that this implicit measure is differentially modulated when experiencing pleasant or aversive odors. We then present an experimental paradigm in which monkeys learn to associate tones with odors, and show that the time delay from the conditioned stimuli to the next breath can be used to measure learning and memory expression in this paradigm. Using this construct, we reveal olfactory performance during acquisition and extinction of odor conditioning. These techniques can be used in electrophysiological recordings from relevant brain areas to shed light on neural networks involved in odor processing and reinforcement-learning.

  10. Pharmacological inhibition of DNA methyltransferase 1 promotes neuronal differentiation from rodent and human nasal olfactory stem/progenitor cell cultures.

    PubMed

    Franco, I; Ortiz-López, L; Roque-Ramírez, B; Ramírez-Rodríguez, G B; Lamas, M

    2017-05-01

    Nasal olfactory stem and neural progenitor cells (NOS/PCs) are considered possible tools for regenerative stem cell therapies in neurodegenerative diseases. Neurogenesis is a complex process regulated by extrinsic and intrinsic signals that include DNA-methylation and other chromatin modifications that could be experimentally manipulated in order to increase neuronal differentiation. The aim of the present study was the characterization of primary cultures and consecutive passages (P2-P10) of NOS/PCs isolated from male Swiss-Webster (mNOS/PCs) or healthy humans (hNOS/PCs). We evaluated and compared cellular morphology, proliferation rates and the expression pattern of pluripotency-associated markers and DNA methylation-associated gene expression in these cultures. Neuronal differentiation was induced by exposure to all-trans retinoic acid and forskolin for 7 days and evaluated by morphological analysis and immunofluorescence against neuronal markers MAP2, NSE and MAP1B. In response to the inductive cues mNOS/PCs expressed NSE (75.67%) and MAP2 (35.34%); whereas the majority of the hNOS/PCs were immunopositive to MAP1B. Treatment with procainamide, a specific inhibitor of DNA methyltransferase 1 (DNMT1), increases in the number of forskolin'/retinoic acid-induced mature neuronal marker-expressing mNOS/PCs cells and enhances neurite development in hNOS/PCs. Our results indicate that mice and human nasal olfactory stem/progenitors cells share pluripotency-related gene expression suggesting that their application for stem cell therapy is worth pursuing and that DNA methylation inhibitors could be efficient tools to enhance neuronal differentiation from these cells.

  11. Smelling is Telling: Human Olfactory Cues Influence Social Judgments in Semi-Realistic Interactions.

    PubMed

    Gaby, Jessica M; Zayas, Vivian

    2017-03-29

    How does a person's smell affect others' impressions of them? Most body odor research asks perceivers to make social judgments based on armpit sweat without perfume or deodorant, presented on t-shirts. Yet, in real life, perceivers encounter fragranced body odor, on whole bodies. Our "raters" wore blindfolds and earplugs and repeatedly smelled same-sex "donors" in live interactions. In one condition, donors wore their normal deodorant and perfume ("diplomatic" odor) while in the other condition, donors were asked to avoid all outside fragrance influences ("natural" odor). We assessed the reliability of social judgments based on such live interactions, and the relationships between live judgments and traditional t-shirt based judgments, and between natural- and diplomatic odor-based judgments. Raters' repeated live social judgments (e.g., friendliness, likeability) were highly consistent for both diplomatic and natural odor, and converged with judgments based on t-shirts. However, social judgments based on natural odor did not consistently predict social judgments based on diplomatic odor, suggesting that natural and diplomatic body odor may convey different types of social information. Our results provide evidence that individuals can perceive reliable, meaningful social olfactory signals from whole bodies, at social distances, regardless of the presence or absence of perfume. Importantly, however, the social value of these signals is modified by the addition of exogenous fragrances. Further, our focus on judgments in same-sex dyads suggests that these olfactory cues hold social value in non-mating contexts. We suggest that future research employ more ecologically relevant methods.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. Human and monkey striatal interneurons are derived from the medial ganglionic eminence but not from the adult subventricular zone.

    PubMed

    Wang, Congmin; You, Yan; Qi, Dashi; Zhou, Xing; Wang, Lei; Wei, Song; Zhang, Zhuangzhi; Huang, Weixi; Liu, Zhidong; Liu, Fang; Ma, Lan; Yang, Zhengang

    2014-08-13

    In adult rodent and monkey brains, newly born neurons in the subventricular zone (SVZ) in the wall of the lateral ventricle migrate into the olfactory bulb (OB) via the rostral migratory stream (RMS). A recent study reported that interneurons are constantly generating in the adult human striatum from the SVZ. In contrast, by taking advantage of the continuous expression of Sp8 from the neuroblast stage through differentiation into mature interneurons, we found that the adult human SVZ does not generate new interneurons for the striatum. In the adult human SVZ and RMS, very few neuroblasts were observed, and most of them expressed the transcription factor Sp8. Neuroblasts in the adult rhesus monkey SVZ-RMS-OB pathway also expressed Sp8. In addition, we observed that Sp8 was expressed by most adult human and monkey OB interneurons. However, very few Sp8+ cells were in the adult human striatum. This suggests that neuroblasts in the adult human SVZ and RMS are likely destined for the OB, but not for the striatum. BrdU-labeling results also revealed few if any newly born neurons in the adult rhesus monkey striatum. Finally, on the basis of transcription factor expression, we provide strong evidence that the vast majority of interneurons in the human and monkey striatum are generated from the medial ganglionic eminence during embryonic developmental stages, as they are in rodents. We conclude that, although a small number of neuroblasts exist in the adult human SVZ, they do not migrate into the striatum and become mature striatal interneurons.

  17. 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

  18. Voltage-Activated Calcium Channels as Functional Markers of Mature Neurons in Human Olfactory Neuroepithelial Cells: Implications for the Study of Neurodevelopment in Neuropsychiatric Disorders

    PubMed Central

    Solís-Chagoyán, Héctor; Flores-Soto, Edgar; Reyes-García, Jorge; Valdés-Tovar, Marcela; Calixto, Eduardo; Montaño, Luis M.; Benítez-King, Gloria

    2016-01-01

    In adulthood, differentiation of precursor cells into neurons continues in several brain structures as well as in the olfactory neuroepithelium. Isolated precursors allow the study of the neurodevelopmental process in vitro. The aim of this work was to determine whether the expression of functional Voltage-Activated Ca2+ Channels (VACC) is dependent on the neurodevelopmental stage in neuronal cells obtained from the human olfactory epithelium of a single healthy donor. The presence of channel-forming proteins in Olfactory Sensory Neurons (OSN) was demonstrated by immunofluorescent labeling, and VACC functioning was assessed by microfluorometry and the patch-clamp technique. VACC were immunodetected only in OSN. Mature neurons responded to forskolin with a five-fold increase in Ca2+. By contrast, in precursor cells, a subtle response was observed. The involvement of VACC in the precursors’ response was discarded for the absence of transmembrane inward Ca2+ movement evoked by step depolarizations. Data suggest differential expression of VACC in neuronal cells depending on their developmental stage and also that the expression of these channels is acquired by OSN during maturation, to enable specialized functions such as ion movement triggered by membrane depolarization. The results support that VACC in OSN could be considered as a functional marker to study neurodevelopment. PMID:27314332

  19. Ultra-high olfactory sensitivity for the human sperm-attractant aromatic aldehyde bourgeonal in CD-1 mice.

    PubMed

    Larsson, Linda; Laska, Matthias

    2011-12-01

    Recent studies have shown that certain aromatic aldehydes are ligands for olfactory receptors expressed in mammalian sperm cells and induce sperm chemotaxis. Using a conditioning paradigm, the olfactory sensitivity of five CD-1 mice for seven aromatic aldehydes was investigated. With all seven stimuli, the mice discriminated concentrations as low as 0.01 ppm (parts per million) from the solvent, and with bourgeonal the animals even detected concentrations as low as 0.1 ppq (parts per quadrillion) which constitutes the lowest olfactory detection threshold value reported in this species so far. The presence of a tertiary butyl group in para-position (relative to the functional aldehyde group) combined with a lack of an additional alkyl group next to the functional aldehyde group may be responsible for the extraordinary sensitivity of the mice for bourgeonal.

  20. 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.

  1. 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.

  2. 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.

  3. Angiogenic properties of adult human thymus fat.

    PubMed

    Salas, Julián; Montiel, Mercedes; Jiménez, Eugenio; Valenzuela, Miguel; Valderrama, José Francisco; Castillo, Rafael; González, Sergio; El Bekay, Rajaa

    2009-11-01

    The endogenous proangiogenic properties of adipose tissue are well recognized. Although the adult human thymus has long been known to degenerate into fat tissue, it has never been considered as a potential source of angiogenic factors. We have investigated the expression of diverse angiogenic factors, including vascular endothelial growth factor A and B, angiopoietin 1, and tyrosine-protein kinase receptor-2 (an angiopoietin receptor), and then analyzed their physiological role on endothelial cell migration and proliferation, two relevant events in angiogenesis. The detection of the gene and protein expression of the various proteins has been performed by immunohistochemistry, Western blotting, and quantitative real-time polymerase chain reaction. We show, for the first time, that adult thymus fat produces a variety of angiogenic factors and induces the proliferation and migration of human umbilical cord endothelial cells. Based on these findings, we suggest that this fat has a potential angiogenic function that might affect thymic function and ongoing adipogenesis within the thymus.

  4. Olfactory receptors for a smell sensor: a comparative study of the electrical responses of rat I7 and human 17-40

    NASA Astrophysics Data System (ADS)

    Alfinito, E.; Millithaler, J.-F.; Reggiani, L.

    2011-12-01

    In this paper, we explore the relevant electrical properties of two olfactory receptors (ORs), one from rat, OR I7, and the other from human, OR 17-40, which are of interest for the realization of smell nanobiosensors. The investigation compares existing experiments, coming from electrochemical impedance spectroscopy, with the theoretical expectations obtained from an impedance network protein analogue, recently developed. The changes in the response due to the sensing action of the proteins are correlated with the conformational change undergone by the single protein. The satisfactory agreement between theory and experiments points to a promising development of a new class of nanobiosensors based on the electrical properties of sensing proteins.

  5. 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.

  6. 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.

  7. Olfactory discrimination ability of human subjects for enantiomers with an isopropenyl group at the chiral center.

    PubMed

    Laska, Matthias

    2004-02-01

    The ability of 20 human subjects to distinguish between nine enantiomeric odor pairs sharing an isopropenyl group at the chiral center was tested in a forced-choice triangular test procedure. I found (i). that as a group, the subjects were only able to significantly discriminate the optical isomers of limonene, carvone, dihydrocarvone, dihydrocarveol and dihydrocarvyl acetate, whereas they failed to distinguish between the (+)- and (-)-forms of perillaalcohol, perillaaldehyde, isopulegol and limonene oxide; (ii). marked interindividual differences in discrimination performance, ranging from subjects who were able to significantly discriminate between eight of the nine odor pairs to subjects who failed to do so with six of the nine tasks; and (iii). that with none of the nine odor pairs the antipodes were reported to differ significantly in subjective intensity when presented at equal concentrations. Additional tests of the chemesthetic potency and threshold measurements of the optical isomers of dihydrocarvone, dihydrocarveol, and dihydrocarvyl acetate suggest that the discriminability of these three enantiomeric odor pairs is indeed due to differences in odor quality. Analysis of structure-activity relationships suggest that the combined presence of (i). an isopropenyl group at the chiral center; (ii). a methyl group at the para-position; and/or (iii). an oxygen-containing group at the meta-position allows for the discrimination of enantiomeric odor pairs.

  8. The scent of salience — Is there olfactory-trigeminal conditioning in humans?

    PubMed Central

    Moessnang, C.; Pauly, K.; Kellermann, T.; Krämer, J.; Finkelmeyer, A.; Hummel, T.; Siegel, S.J.; Schneider, F.; Habel, U.

    2014-01-01

    Pavlovian fear conditioning has been thoroughly studied in the visual, auditory and somatosensory domain, but evidence is scarce with regard to the chemosensory modality. Under the assumption that Pavlovian conditioning relies on the supra-modal mechanism of salience attribution, the present study was set out to attest the existence of chemosensory aversive conditioning in humans as a specific instance of salience attribution. fMRI was performed in 29 healthy subjects during a differential aversive conditioning paradigm. Two odors (rose, vanillin) served as conditioned stimuli (CS), one of which (CS+) was intermittently coupled with intranasally administered CO2. On the neural level, a robust differential response to the CS+ emerged in frontal, temporal, occipito-parietal and subcortical brain regions, including the amygdala. These changes were paralleled by the development of a CS+-specific connectivity profile of the anterior midcingulate cortex (aMCC), which is a key structure for processing salience information in order to guide adaptive response selection. Increased coupling could be found between key nodes of the salience network (anterior insula, neo-cerebellum) and sensorimotor areas, representing putative input and output structures of the aMCC for exerting adaptive motor control. In contrast, behavioral and skin conductance responses did not show significant effects of conditioning, which has been attributed to contingency unawareness. These findings imply substantial similarities of conditioning involving chemosensory and other sensory modalities, and suggest that salience attribution and adaptive control represent a general, modality-independent principle underlying Pavlovian conditioning. PMID:23558094

  9. 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.

  10. [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.

  11. 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

  12. 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.

  13. 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.

  14. Uniquely hominid features of adult human astrocytes.

    PubMed

    Oberheim, Nancy Ann; Takano, Takahiro; Han, Xiaoning; He, Wei; Lin, Jane H C; Wang, Fushun; Xu, Qiwu; Wyatt, Jeffrey D; Pilcher, Webster; Ojemann, Jeffrey G; Ransom, Bruce R; Goldman, Steven A; Nedergaard, Maiken

    2009-03-11

    Defining the microanatomic differences between the human brain and that of other mammals is key to understanding its unique computational power. Although much effort has been devoted to comparative studies of neurons, astrocytes have received far less attention. We report here that protoplasmic astrocytes in human neocortex are 2.6-fold larger in diameter and extend 10-fold more GFAP (glial fibrillary acidic protein)-positive primary processes than their rodent counterparts. In cortical slices prepared from acutely resected surgical tissue, protoplasmic astrocytes propagate Ca(2+) waves with a speed of 36 microm/s, approximately fourfold faster than rodent. Human astrocytes also transiently increase cystosolic Ca(2+) in response to glutamatergic and purinergic receptor agonists. The human neocortex also harbors several anatomically defined subclasses of astrocytes not represented in rodents. These include a population of astrocytes that reside in layers 5-6 and extend long fibers characterized by regularly spaced varicosities. Another specialized type of astrocyte, the interlaminar astrocyte, abundantly populates the superficial cortical layers and extends long processes without varicosities to cortical layers 3 and 4. Human fibrous astrocytes resemble their rodent counterpart but are larger in diameter. Thus, human cortical astrocytes are both larger, and structurally both more complex and more diverse, than those of rodents. On this basis, we posit that this astrocytic complexity has permitted the increased functional competence of the adult human brain.

  15. 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

  16. 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.

  17. 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

  18. Burkholderia pseudomallei Capsule Exacerbates Respiratory Melioidosis but Does Not Afford Protection against Antimicrobial Signaling or Bacterial Killing in Human Olfactory Ensheathing Cells

    PubMed Central

    Dando, Samantha J.; Ipe, Deepak S.; Batzloff, Michael; Sullivan, Matthew J.; Crossman, David K.; Crowley, Michael; Strong, Emily; Kyan, Stephanie; Leclercq, Sophie Y.; Ekberg, Jenny A. K.; St. John, James

    2016-01-01

    Melioidosis, caused by the bacterium Burkholderia pseudomallei, is an often severe infection that regularly involves respiratory disease following inhalation exposure. Intranasal (i.n.) inoculation of mice represents an experimental approach used to study the contributions of bacterial capsular polysaccharide I (CPS I) to virulence during acute disease. We used aerosol delivery of B. pseudomallei to establish respiratory infection in mice and studied CPS I in the context of innate immune responses. CPS I improved B. pseudomallei survival in vivo and triggered multiple cytokine responses, neutrophil infiltration, and acute inflammatory histopathology in the spleen, liver, nasal-associated lymphoid tissue, and olfactory mucosa (OM). To further explore the role of the OM response to B. pseudomallei infection, we infected human olfactory ensheathing cells (OECs) in vitro and measured bacterial invasion and the cytokine responses induced following infection. Human OECs killed >90% of the B. pseudomallei in a CPS I-independent manner and exhibited an antibacterial cytokine response comprising granulocyte colony-stimulating factor, tumor necrosis factor alpha, and several regulatory cytokines. In-depth genome-wide transcriptomic profiling of the OEC response by RNA-Seq revealed a network of signaling pathways activated in OECs following infection involving a novel group of 378 genes that encode biological pathways controlling cellular movement, inflammation, immunological disease, and molecular transport. This represents the first antimicrobial program to be described in human OECs and establishes the extensive transcriptional defense network accessible in these cells. Collectively, these findings show a role for CPS I in B. pseudomallei survival in vivo following inhalation infection and the antibacterial signaling network that exists in human OM and OECs. PMID:27091931

  19. Generation of pluripotent stem cells from adult human testis.

    PubMed

    Conrad, Sabine; Renninger, Markus; Hennenlotter, Jörg; Wiesner, Tina; Just, Lothar; Bonin, Michael; Aicher, Wilhelm; Bühring, Hans-Jörg; Mattheus, Ulrich; Mack, Andreas; Wagner, Hans-Joachim; Minger, Stephen; Matzkies, Matthias; Reppel, Michael; Hescheler, Jürgen; Sievert, Karl-Dietrich; Stenzl, Arnulf; Skutella, Thomas

    2008-11-20

    Human primordial germ cells and mouse neonatal and adult germline stem cells are pluripotent and show similar properties to embryonic stem cells. Here we report the successful establishment of human adult germline stem cells derived from spermatogonial cells of adult human testis. Cellular and molecular characterization of these cells revealed many similarities to human embryonic stem cells, and the germline stem cells produced teratomas after transplantation into immunodeficient mice. The human adult germline stem cells differentiated into various types of somatic cells of all three germ layers when grown under conditions used to induce the differentiation of human embryonic stem cells. We conclude that the generation of human adult germline stem cells from testicular biopsies may provide simple and non-controversial access to individual cell-based therapy without the ethical and immunological problems associated with human embryonic stem cells.

  20. Dose-Response Functions for the Olfactory, Nasal Trigeminal, and Ocular Trigeminal Detectability of Airborne Chemicals by Humans.

    PubMed

    Cometto-Muñiz, J Enrique; Abraham, Michael H

    2016-01-01

    We gathered from the literature 47 odor and 37 trigeminal (nasal and ocular) chemesthetic psychometric (i.e., detectability or dose-response) functions from a group of 41 chemicals. Vapors delivered were quantified by analytical methods. All functions were very well fitted by the sigmoid (logistic) equation: y = 1 / (1 + e({-(x-C)/D})), where parameter C quantifies the detection threshold concentration and parameter D the steepness of the function. Odor and chemesthetic functions showed no concentration overlap: olfactory functions grew along the parts per billion (ppb by volume) range or lower, whereas trigeminal functions grew along the part per million (ppm by volume) range. Although, on average, odor detectability rose from chance detection to perfect detection within 2 orders of magnitude in concentration, chemesthetic detectability did it within one. For 16 compounds having at least 1 odor and 1 chemesthetic function, the average gap between the 2 functions was 4.6 orders of magnitude in concentration. A quantitative structure-activity relationship (QSAR) using 5 chemical descriptors that had previously described stand-alone odor and chemesthetic threshold values, also holds promise to describe, and eventually predict, olfactory and chemesthetic detectability functions, albeit functions from additional compounds are needed to strengthen the QSAR.

  1. 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

  2. Latent inhibition in human adults without masking.

    PubMed

    Escobar, Martha; Arcediano, Francisco; Miller, Ralph R

    2003-09-01

    Latent inhibition refers to attenuated responding to Cue X observed when the X-outcome pairings are preceded by X-alone presentations. It has proven difficult to obtain in human adults unless the preexposure (X-alone) presentations are embedded within a masking (i.e., distracting) task. The authors hypothesized that the difficulty in obtaining latent inhibition with unmasked tasks is related to the usual training procedures, in which the preexposure and conditioning experiences are separated by a set of instructions. Experiment 1 reports latent inhibition without masking in a task in which preexposure and conditioning occur without interruption. Experiments 2 and 3 demonstrate that this attenuation in responding to target Cue X does not pass a summation test for conditioned inhibition and is context specific, thereby confirming that it is latent inhibition. Experiments 3 and 4 confirm that introducing instructions between preexposure and conditioning disrupts latent inhibition.

  3. Astrocitary niches in human adult medulla oblongata.

    PubMed

    Rusu, Mugurel Constantin; Dermengiu, Dan; Loreto, Carla; Motoc, Andrei Gheorghe Marius; Pop, Elena

    2013-04-01

    Astrocytes are considered as neuromodulators of the CNS. Whereas experimental studies on astrocitary functions are gaining importance, the anatomy of the astrocitary niches in the human CNS has been overlooked. The study was performed on the brainstem of 10 adult cadavers. We aimed to determine astrocitary niches in the human medulla oblongata using immunohistochemical labeling with vimentin and also CD34 immunostaining to accurately diagnose associated microvessels. Niches rich in astrocytes were identified as follows: (a) the superficial layer of astrocytes, ventral and ventrolateral, in the rostral medulla oblongata; (b) the median raphe; (c) medullary nuclei: arcuate nucleus, area postrema, nucleus of the solitary tract; (d) the subependymal zone (SEZ, caudal medulla) and subventricular zone (SVZ, rostral medulla). Astrocytes were scarce in the ventrolateral medulla, and mostly present within the pyramidal tract and the olivary nucleus. Apart from the SEZ and SVZ, the brainstem niches of astrocytes mostly overlap those regions known to perform roles as central respiratory chemoreceptors. The astrocytes of the SEZ and SVZ, which are known as stem cell niches, are related to an increased microvascular density.

  4. 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.

  5. Have you got any cholesterol? Adults' views of human nutrition

    NASA Astrophysics Data System (ADS)

    Schibeci, Renato; Wong, Khoon Yoong

    1994-12-01

    The general aim of our human nutrition project is to develop a health education model grounded in ‘everyday’ or ‘situated’ cognition (Hennessey, 1993). In 1993, we began pilot work to document adult understanding of human nutrition. We used a HyperCard stack as the basis for a series of interviews with 50 adults (25 university students, and 25 adults from offcampus). The interviews were transcribed and analysed using the NUDIST computer program. A summary of the views of these 50 adults on selected aspects of human nutrition is presented in this paper.

  6. Encephalitis-Associated Human Metapneumovirus Pneumonia in Adult, Australia.

    PubMed

    Fok, Anthony; Mateevici, Cristina; Lin, Belinda; Chandra, Ronil V; Chong, Victor H T

    2015-11-01

    Human metapneumovirus pneumonia, most commonly found in children, was diagnosed in an adult with encephalitis. This case suggests that testing for human metapneumovirus RNA in nasopharyngeal aspirate and cerebrospinal fluid samples should be considered in adults with encephalitis who have a preceding respiratory infection.

  7. Adult Education & Human Resource Development: Overlapping and Disparate Fields

    ERIC Educational Resources Information Center

    Watkins, Karen E.; Marsick, Victoria J.

    2014-01-01

    Adult education and human resource development as fields of practice and study share some roots in common but have grown in different directions in their histories. Adult education's roots focused initially on citizenship for a democratic society, whereas human resource development's roots are in performance at work. While they have…

  8. 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

  9. 21 CFR 874.1600 - Olfactory test device.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Olfactory test device. 874.1600 Section 874.1600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Diagnostic Devices § 874.1600 Olfactory test device....

  10. 21 CFR 874.1600 - Olfactory test device.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Olfactory test device. 874.1600 Section 874.1600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Diagnostic Devices § 874.1600 Olfactory test device....

  11. 21 CFR 874.1600 - Olfactory test device.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Olfactory test device. 874.1600 Section 874.1600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Diagnostic Devices § 874.1600 Olfactory test device....

  12. Adult human brain cell culture for neuroscience research.

    PubMed

    Gibbons, Hannah M; Dragunow, Mike

    2010-06-01

    Studies of the brain have progressed enormously through the use of in vivo and in vitro non-human models. However, it is unlikely such studies alone will unravel the complexities of the human brain and so far no neuroprotective treatment developed in animals has worked in humans. In this review we discuss the use of adult human brain cell culture methods in brain research to unravel the biology of the normal and diseased human brain. The advantages of using adult human brain cells as tools to study human brain function from both historical and future perspectives are discussed. In particular, studies using dissociated cultures of adult human microglia, astrocytes, oligodendrocytes and neurons are described and the applications of these types of study are evaluated. Alternative sources of human brain cells such as adult neural stem cells, induced pluripotent stem cells and slice cultures of adult human brain tissue are also reviewed. These adult human brain cell culture methods could benefit basic research and more importantly, facilitate the translation of basic neuroscience research to the clinic for the treatment of brain disorders.

  13. 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.

  14. 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

  15. 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.

  16. Effects of Human Alpha-Synuclein A53T-A30P Mutations on SVZ and Local Olfactory Bulb Cell Proliferation in a Transgenic Rat Model of Parkinson Disease.

    PubMed

    Lelan, Faustine; Boyer, Cécile; Thinard, Reynald; Rémy, Séverine; Usal, Claire; Tesson, Laurent; Anegon, Ignacio; Neveu, Isabelle; Damier, Philippe; Naveilhan, Philippe; Lescaudron, Laurent

    2011-01-01

    A transgenic Sprague Dawley rat bearing the A30P and A53T α-synuclein (α-syn) human mutations under the control of the tyrosine hydroxylase promoter was generated in order to get a better understanding of the role of the human α-syn mutations on the neuropathological events involved in the progression of the Parkinson's disease (PD). This rat displayed olfactory deficits in the absence of motor impairments as observed in most early PD cases. In order to investigate the role of the mutated α-syn on cell proliferation, we focused on the subventricular zone (SVZ) and the olfactory bulbs (OB) as a change of the proliferation could affect OB function. The effect on OB dopaminergic innervation was investigated. The human α-syn co-localized in TH-positive OB neurons. No human α-syn was visualized in the SVZ. A significant increase in resident cell proliferation in the glomerular but not in the granular layers of the OB and in the SVZ was observed. TH innervation was significantly increased within the glomerular layer without an increase in the size of the glomeruli. Our rat could be a good model to investigate the role of human mutated α-syn on the development of olfactory deficits.

  17. 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

  18. Adult Human Neurogenesis: From Microscopy to Magnetic Resonance Imaging

    PubMed Central

    Sierra, Amanda; Encinas, Juan M.; Maletic-Savatic, Mirjana

    2011-01-01

    Neural stem cells reside in well-defined areas of the adult human brain and are capable of generating new neurons throughout the life span. In rodents, it is well established that the new born neurons are involved in olfaction as well as in certain forms of memory and learning. In humans, the functional relevance of adult human neurogenesis is being investigated, in particular its implication in the etiopathology of a variety of brain disorders. Adult neurogenesis in the human brain was discovered by utilizing methodologies directly imported from the rodent research, such as immunohistological detection of proliferation and cell-type specific biomarkers in postmortem or biopsy tissue. However, in the vast majority of cases, these methods do not support longitudinal studies; thus, the capacity of the putative stem cells to form new neurons under different disease conditions cannot be tested. More recently, new technologies have been specifically developed for the detection and quantification of neural stem cells in the living human brain. These technologies rely on the use of magnetic resonance imaging, available in hospitals worldwide. Although they require further validation in rodents and primates, these new methods hold the potential to test the contribution of adult human neurogenesis to brain function in both health and disease. This review reports on the current knowledge on adult human neurogenesis. We first review the different methods available to assess human neurogenesis, both ex vivo and in vivo and then appraise the changes of adult neurogenesis in human diseases. PMID:21519376

  19. Adult human neurogenesis: from microscopy to magnetic resonance imaging.

    PubMed

    Sierra, Amanda; Encinas, Juan M; Maletic-Savatic, Mirjana

    2011-01-01

    Neural stem cells reside in well-defined areas of the adult human brain and are capable of generating new neurons throughout the life span. In rodents, it is well established that the new born neurons are involved in olfaction as well as in certain forms of memory and learning. In humans, the functional relevance of adult human neurogenesis is being investigated, in particular its implication in the etiopathology of a variety of brain disorders. Adult neurogenesis in the human brain was discovered by utilizing methodologies directly imported from the rodent research, such as immunohistological detection of proliferation and cell-type specific biomarkers in postmortem or biopsy tissue. However, in the vast majority of cases, these methods do not support longitudinal studies; thus, the capacity of the putative stem cells to form new neurons under different disease conditions cannot be tested. More recently, new technologies have been specifically developed for the detection and quantification of neural stem cells in the living human brain. These technologies rely on the use of magnetic resonance imaging, available in hospitals worldwide. Although they require further validation in rodents and primates, these new methods hold the potential to test the contribution of adult human neurogenesis to brain function in both health and disease. This review reports on the current knowledge on adult human neurogenesis. We first review the different methods available to assess human neurogenesis, both ex vivo and in vivo and then appraise the changes of adult neurogenesis in human diseases.

  20. [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.

  1. 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

  2. Developing Resourceful Humans. Adult Education within the Economic Context.

    ERIC Educational Resources Information Center

    Burton, Lynn Elen, Ed.

    This book, which explores the shifting paradigm from human resource development to developing resourceful humans, establishes the historical position of adult education within the economic context, discusses human capital propositions, and examines the learning dimensions of economic and educational change. The following chapters are included:…

  3. 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.

  4. Adult Literacy Education and Human Rights: A View from Afghanistan

    ERIC Educational Resources Information Center

    Andersen, Susan M.; Kooij, Christina S.

    2007-01-01

    In this article, we argue that adult literacy as part of international development is an issue of both human rights and women's rights. We explore this by presenting a case study of the effects of one innovative adult literacy program in Afghanistan that places men and women, as well as various ethnicities, together in the same classroom as…

  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. 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.

  7. 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

  8. 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.

  9. A comparative study of bifidobacteria in human babies and adults

    PubMed Central

    KHONSARI, Shadi; SUGANTHY, Mayuran; BURCZYNSKA, Beata; DANG, Vu; CHOUDHURY, Manika; PACHENARI, Azra

    2015-01-01

    The composition and diversity of the gut microbiota are known to be different between babies and adults. The aim of this project was to compare the level of bifidobacteria between babies and adults and to investigate the influence of lifestyle factors on the level of this bacterium in the gut. During this study, the levels of bifidobacteria in 10 human babies below 2 years of age were compared with that of 10 human adults above 40 years. The level of bifidobacteria proved to be significantly higher in babies in comparison with adults. This investigation concluded that a combination of several factors, such as age, diet, and BMI, has an important effect on the level of bifidobacteria in adults, while in babies, a combination of diet and age may influence the level of intestinal bifidobacteria. PMID:27200263

  10. Distorted Coarse Axon Targeting and Reduced Dendrite Connectivity Underlie Dysosmia after Olfactory Axon Injury

    PubMed Central

    Iwata, Ryo; Fujimoto, Satoshi; Aihara, Shuhei

    2016-01-01

    The glomerular map in the olfactory bulb (OB) is the basis for odor recognition. Once established during development, the glomerular map is stably maintained throughout the life of an animal despite the continuous turnover of olfactory sensory neurons (OSNs). However, traumatic damage to OSN axons in the adult often leads to dysosmia, a qualitative and quantitative change in olfaction in humans. A mouse model of dysosmia has previously indicated that there is an altered glomerular map in the OB after the OSN axon injury; however, the underlying mechanisms that cause the map distortion remain unknown. In this study, we examined how the glomerular map is disturbed and how the odor information processing in the OB is affected in the dysosmia model mice. We found that the anterior–posterior coarse targeting of OSN axons is disrupted after OSN axon injury, while the local axon sorting mechanisms remained. We also found that the connectivity of mitral/tufted cell dendrites is reduced after injury, leading to attenuated odor responses in mitral/tufted cells. These results suggest that existing OSN axons are an essential scaffold for maintaining the integrity of the olfactory circuit, both OSN axons and mitral/tufted cell dendrites, in the adult. PMID:27785463

  11. 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

  12. Humanities and the Adult Learner in an Information Society.

    ERIC Educational Resources Information Center

    Myers, Dale; Kamholtz, Jonathan

    Humanities courses have often been given little attention in continuing education for adults, possibly because they have been viewed as not "practical" or not "job-oriented" enough in our career-oriented, technologically advanced society. However, the humanities should be an integral part of our culture and of the lives of…

  13. Organization of olfactory centres in the malaria mosquito Anopheles gambiae

    PubMed Central

    Riabinina, Olena; Task, Darya; Marr, Elizabeth; Lin, Chun-Chieh; Alford, Robert; O'Brochta, David A.; Potter, Christopher J.

    2016-01-01

    Mosquitoes are vectors for multiple infectious human diseases and use a variety of sensory cues (olfactory, temperature, humidity and visual) to locate a human host. A comprehensive understanding of the circuitry underlying sensory signalling in the mosquito brain is lacking. Here we used the Q-system of binary gene expression to develop transgenic lines of Anopheles gambiae in which olfactory receptor neurons expressing the odorant receptor co-receptor (Orco) gene are labelled with GFP. These neurons project from the antennae and maxillary palps to the antennal lobe (AL) and from the labella on the proboscis to the suboesophageal zone (SEZ), suggesting integration of olfactory and gustatory signals occurs in this brain region. We present detailed anatomical maps of olfactory innervations in the AL and the SEZ, identifying glomeruli that may respond to human body odours or carbon dioxide. Our results pave the way for anatomical and functional neurogenetic studies of sensory processing in mosquitoes. PMID:27694947

  14. 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.

  15. Differentiated human stem cells resemble fetal, not adult, β cells.

    PubMed

    Hrvatin, Sinisa; O'Donnell, Charles W; Deng, Francis; Millman, Jeffrey R; Pagliuca, Felicia Walton; DiIorio, Philip; Rezania, Alireza; Gifford, David K; Melton, Douglas A

    2014-02-25

    Human pluripotent stem cells (hPSCs) have the potential to generate any human cell type, and one widely recognized goal is to make pancreatic β cells. To this end, comparisons between differentiated cell types produced in vitro and their in vivo counterparts are essential to validate hPSC-derived cells. Genome-wide transcriptional analysis of sorted insulin-expressing (INS(+)) cells derived from three independent hPSC lines, human fetal pancreata, and adult human islets points to two major conclusions: (i) Different hPSC lines produce highly similar INS(+) cells and (ii) hPSC-derived INS(+) (hPSC-INS(+)) cells more closely resemble human fetal β cells than adult β cells. This study provides a direct comparison of transcriptional programs between pure hPSC-INS(+) cells and true β cells and provides a catalog of genes whose manipulation may convert hPSC-INS(+) cells into functional β cells.

  16. 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.

  17. 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.

  18. Machine-learned pattern identification in olfactory subtest results

    PubMed Central

    Lötsch, Jörn; Hummel, Thomas; Ultsch, Alfred

    2016-01-01

    The human sense of smell is often analyzed as being composed of three main components comprising olfactory threshold, odor discrimination and the ability to identify odors. A relevant distinction of the three components and their differential changes in distinct disorders remains a research focus. The present data-driven analysis aimed at establishing a cluster structure in the pattern of olfactory subtest results. Therefore, unsupervised machine-learning was applied onto olfactory subtest results acquired in 10,714 subjects with nine different olfactory pathologies. Using the U-matrix, Emergent Self-organizing feature maps (ESOM) identified three different clusters characterized by (i) low threshold and good discrimination and identification, (ii) very high threshold associated with absent to poor discrimination and identification ability, or (iii) medium threshold, i.e., in the mid-range of possible thresholds, associated with reduced discrimination and identification ability. Specific etiologies of olfactory (dys)function were unequally represented in the clusters (p < 2.2 · 10−16). Patients with congenital anosmia were overrepresented in the second cluster while subjects with postinfectious olfactory dysfunction belonged frequently to the third cluster. However, the clusters provided no clear separation between etiologies. Hence, the present verification of a distinct cluster structure encourages continued scientific efforts at olfactory test pattern recognition. PMID:27762302

  19. Late Pleistocene adult mortality patterns and modern human establishment

    PubMed Central

    Trinkaus, Erik

    2011-01-01

    The establishment of modern humans in the Late Pleistocene, subsequent to their emergence in eastern Africa, is likely to have involved substantial population increases, during their initial dispersal across southern Asia and their subsequent expansions throughout Africa and into more northern Eurasia. An assessment of younger (20–40 y) versus older (>40 y) adult mortality distributions for late archaic humans (principally Neandertals) and two samples of early modern humans (Middle Paleolithic and earlier Upper Paleolithic) provides little difference across the samples. All three Late Pleistocene samples have a dearth of older individuals compared with Holocene ethnographic/historical samples. They also lack older adults compared with Holocene paleodemographic profiles that have been critiqued for having too few older individuals for subsistence, social, and demographic viability. Although biased, probably through a combination of preservation, age assessment, and especially Pleistocene mobility requirements, these adult mortality distributions suggest low life expectancy and demographic instability across these Late Pleistocene human groups. They indicate only subtle and paleontologically invisible changes in human paleodemographics with the establishment of modern humans; they provide no support for a life history advantage among early modern humans. PMID:21220336

  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. Linking adult hippocampal neurogenesis with human physiology and disease.

    PubMed

    Bowers, Megan; Jessberger, Sebastian

    2016-07-01

    We here review the existing evidence linking adult hippocampal neurogenesis and human brain function in physiology and disease. Furthermore, we aim to point out where evidence is missing, highlight current promising avenues of investigation, and suggest future tools and approaches to foster the link between life-long neurogenesis and human brain function. Developmental Dynamics 245:702-709, 2016. © 2016 Wiley Periodicals, Inc.

  3. Expansion of Multipotent Stem Cells from the Adult Human Brain

    PubMed Central

    Murrell, Wayne; Palmero, Emily; Bianco, John; Stangeland, Biljana; Joel, Mrinal; Paulson, Linda; Thiede, Bernd; Grieg, Zanina; Ramsnes, Ingunn; Skjellegrind, Håvard K.; Nygård, Ståle; Brandal, Petter; Sandberg, Cecilie; Vik-Mo, Einar; Palmero, Sheryl; Langmoen, Iver A.

    2013-01-01

    The discovery of stem cells in the adult human brain has revealed new possible scenarios for treatment of the sick or injured brain. Both clinical use of and preclinical research on human adult neural stem cells have, however, been seriously hampered by the fact that it has been impossible to passage these cells more than a very few times and with little expansion of cell numbers. Having explored a number of alternative culturing conditions we here present an efficient method for the establishment and propagation of human brain stem cells from whatever brain tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency proteins Sox2 and Oct4 are expressed without artificial induction. For the first time multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells’ behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient’s own-derived stem cells. PMID:23967194

  4. Maps of the adult human hypothalamus

    PubMed Central

    Lemaire, Jean-Jacques; Nezzar, Hachemi; Sakka, Laurent; Boirie, Yves; Fontaine, Denys; Coste, Aurélien; Coll, Guillaume; Sontheimer, Anna; Sarret, Catherine; Gabrillargues, Jean; De Salles, Antonio

    2013-01-01

    The human hypothalamus is a small deeply located region placed at the crossroad of neurovegetative, neuroendocrine, limbic, and optic systems. Although deep brain stimulation techniques have proven that it could be feasible to modulate these systems, targeting the hypothalamus and in particular specific nuclei and white bundles, is still challenging. Our goal was to make a synthesis of relevant topographical data of the human hypothalamus, under the form of magnetic resonance imaging maps useful for mastering its elaborated structure as well as its neighborhood. As from 1.5 Tesla, Inversion-Recovery sequence allows locating the hypothalamus and most of its components. Spotting hypothalamic compartments is possible according to specific landmarks: the anterior commissure, the mammillary bodies, the preoptic recess, the infundibular recess, the crest between the preoptic and the infundibular recesses, the optical tract, the fornix, and the mammillo-thalamic bundle. The identification of hypothalamus and most of its components could be useful to allow the quantification of local pathological processes and to target specific circuitry to alleviate severe symptoms, using physical or biological agents. PMID:23682342

  5. Serotonin is critical for rewarded olfactory short-term memory in Drosophila.

    PubMed

    Sitaraman, Divya; LaFerriere, Holly; Birman, Serge; Zars, Troy

    2012-06-01

    The biogenic amines dopamine, octopamine, and serotonin are critical in establishing normal memories. A common view for the amines in insect memory performance has emerged in which dopamine and octopamine are largely responsible for aversive and appetitive memories. Examination of the function of serotonin begins to challenge the notion of one amine type per memory because altering serotonin function also reduces aversive olfactory memory and place memory levels. Could the function of serotonin be restricted to the aversive domain, suggesting a more specific dopamine/serotonin system interaction? The function of the serotonergic system in appetitive olfactory memory was examined. By targeting the tetanus toxin light chain (TNT) and the human inwardly rectifying potassium channel (Kir2.1) to the serotonin neurons with two different GAL4 driver combinations, the serotonergic system was inhibited. Additional use of the GAL80(ts1) system to control expression of transgenes to the adult stage of the life cycle addressed a potential developmental role of serotonin in appetitive memory. Reduction in appetitive olfactory memory performance in flies with these transgenic manipulations, without altering control behaviors, showed that the serotonergic system is also required for normal appetitive memory. Thus, serotonin appears to have a more general role in Drosophila memory, and implies an interaction with both the dopaminergic and octopaminergic systems.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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.

  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. Rasagiline Ameliorates Olfactory Deficits in an Alpha-Synuclein Mouse Model of Parkinson's Disease

    PubMed Central

    Petit, Géraldine H.; Berkovich, Elijahu; Hickery, Mark; Kallunki, Pekka; Fog, Karina; Fitzer-Attas, Cheryl; Brundin, Patrik

    2013-01-01

    Impaired olfaction is an early pre-motor symptom of Parkinson's disease. The neuropathology underlying olfactory dysfunction in Parkinson's disease is unknown, however α-synuclein accumulation/aggregation and altered neurogenesis might play a role. We characterized olfactory deficits in a transgenic mouse model of Parkinson's disease expressing human wild-type α-synuclein under the control of the mouse α-synuclein promoter. Preliminary clinical observations suggest that rasagiline, a monoamine oxidase-B inhibitor, improves olfaction in Parkinson's disease. We therefore examined whether rasagiline ameliorates olfactory deficits in this Parkinson's disease model and investigated the role of olfactory bulb neurogenesis. α-Synuclein mice were progressively impaired in their ability to detect odors, to discriminate between odors, and exhibited alterations in short-term olfactory memory. Rasagiline treatment rescued odor detection and odor discrimination abilities. However, rasagiline did not affect short-term olfactory memory. Finally, olfactory changes were not coupled to alterations in olfactory bulb neurogenesis. We conclude that rasagiline reverses select olfactory deficits in a transgenic mouse model of Parkinson's disease. The findings correlate with preliminary clinical observations suggesting that rasagiline ameliorates olfactory deficits in Parkinson's disease. PMID:23573275

  17. Olfactory Function in Wave 2 of the National Social Life, Health, and Aging Project

    PubMed Central

    Wroblewski, Kristen E.; Schumm, L. Philip; Pinto, Jayant M.; Chen, Rachel C.; McClintock, Martha K.

    2014-01-01

    Objective. To investigate the sense of smell, including sensitivity and odor identification, and characterize the U.S. national prevalence of olfactory dysfunction in older adults, thereby facilitating further investigation of the substantial risks for older adults associated with this basic sensory ability. Method. The sense of smell was evaluated using the Olfactory Function Field Exam (OFFE), a measure designed specifically for field research, which assesses 3 components of olfaction: sensitivity to n-butanol (a standard testing odorant) and androstadienone (AND, a key social odor produced by humans), as well as the ability to identify odors. Respondents were randomly selected from the National Social Life, Health, and Aging Project Wave 2 sample to receive the OFFE (n = 2,304), and 2,212 consented to participate. Results. In the U.S. population aged 62–90, n-butanol detection ability was significantly worse at older ages (ordinal logistic regression, p < .001); however, there was no difference in detection ability between genders (p = .60). AND detection ability was also significantly worse at older ages (p = .003), but in contrast to n-butanol, women outperformed men (p = .001). As expected, odor identification ability was worse in older people than in younger (p < .001), and women were more accurate than men (p = .001). Discussion. We report for the first time 3 facets of olfactory function and its association with age and gender in a representative sample of U.S. older adults. Future analyses of these data are needed to elucidate the sense of smell’s role in physical, social, and mental health with aging. PMID:25360014

  18. 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.

  19. 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

  20. 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...

  1. 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

  2. I can see, hear, and smell your fear: comparing olfactory and audiovisual media in fear communication.

    PubMed

    de Groot, Jasper H B; Semin, Gün R; Smeets, Monique A M

    2014-04-01

    Recent evidence suggests that humans can become fearful after exposure to olfactory fear signals, yet these studies have reported the effects of fear chemosignals without examining emotion-relevant input from traditional communication modalities (i.e., vision, audition). The question that we pursued here was therefore: How significant is an olfactory fear signal in the broader context of audiovisual input that either confirms or contradicts olfactory information? To test this, we manipulated olfactory (fear, no fear) and audiovisual (fear, no fear) information and demonstrated that olfactory fear signals were as potent as audiovisual fear signals in eliciting a fearful facial expression. Irrespective of confirmatory or contradictory audiovisual information, olfactory fear signals produced by senders induced fear in receivers outside of conscious access. These findings run counter to traditional views that emotions are communicated exclusively via visual and linguistic channels.

  3. 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

  4. 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.

  5. Bacteriology of moderate (chronic) periodontitis in mature adult humans.

    PubMed Central

    Moore, W E; Holdeman, L V; Cato, E P; Smibert, R M; Burmeister, J A; Ranney, R R

    1983-01-01

    A total of 171 taxa was represented among 1,900 bacterial isolates from 60 samples of sites affected with moderate periodontitis in 22 mature adult humans. The composition of the subgingival sulcus flora was statistically significantly different from that of the adjacent supragingival flora and the subgingival flora of 14 people with healthy gingiva, but was not significantly different from that of sulci affected with severe periodontitis in 21 young human adults. The sulcus floras of moderate periodontitis and severe periodontitis shared many of their predominant bacterial species, but there were differences in the relative proportions of some of these species. Similar relationships were found for seven taxa of treponemes that were cultured from the samples. PMID:6642641

  6. 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.

  7. Lymphatic Stomata in the Adult Human Pulmonary Ligament

    PubMed Central

    Miura, Masahiro; Iobe, Hiroaki; Kudo, Tomoo; Shimazu, Yoshihito; Aoba, Takaaki; Okudela, Koji; Nagahama, Kiyotaka; Sakamaki, Kentaro; Yoshida, Maki; Nagao, Toshitaka; Nakaya, Takeo; Kurata, Atsushi; Ohtani, Osamu

    2015-01-01

    Abstract Background: Lymphatic stomata are small lymphatic openings in the serosal membrane that communicate with the serosal cavity. Although these stomata have primarily been studied in experimental mammals, little is known concerning the presence and properties of lymphatic stomata in the adult human pleura. Thus, adult human pleurae were examined for the presence or absence of lymphatic stomata. Methods and Results: A total of 26 pulmonary ligaments (13 left and 13 right) were obtained from 15 adult human autopsy cases and examined using electron and light microscopy. The microscopic studies revealed the presence of apertures fringed with D2-40-positive, CD31-positive, and cytokeratin-negative endothelial cells directly communicating with submesothelial lymphatics in all of the pulmonary ligaments. The apertures' sizes and densities varied from case to case according to the serial tissue section. The medians of these aperture sizes ranged from 2.25 to 8.75 μm in the left pulmonary ligaments and from 2.50 to 12.50 μm in the right pulmonary ligaments. The densities of the apertures ranged from 2 to 9 per mm2 in the left pulmonary ligaments and from 2 to 18 per mm2 in the right pulmonary ligaments. However, no significant differences were found regarding the aperture size (p=0.359) and density (p=0.438) between the left and the right pulmonary ligaments. Conclusions: Our study revealed that apertures exhibit structural adequacy as lymphatic stomata on the surface of the pulmonary ligament, thereby providing evidence that lymphatic stomata are present in the adult human pleura. PMID:25526320

  8. Doublecortin expression in the normal and epileptic adult human brain.

    PubMed

    Liu, Y W J; Curtis, M A; Gibbons, H M; Mee, E W; Bergin, P S; Teoh, H H; Connor, B; Dragunow, M; Faull, R L M

    2008-12-01

    Mesial temporal lobe epilepsy (MTLE) is a neurological disorder associated with spontaneous recurrent complex partial seizures and hippocampal sclerosis. Although increased hippocampal neurogenesis has been reported in animal models of MTLE, increased neurogenesis has not been reported in the hippocampus of adult human MTLE cases. Here we showed that cells expressing doublecortin (Dcx), a microtubule-associated protein expressed in migrating neuroblasts, were present in the hippocampus and temporal cortex of the normal and MTLE adult human brain. In particular, increased numbers of Dcx-positive cells were observed in the epileptic compared with the normal temporal cortex. Importantly, 56% of Dcx-expressing cells in the epileptic temporal cortex coexpressed both the proliferative cell marker, proliferating cell nuclear antigen and early neuronal marker, TuJ1, suggesting that they may be newly generated neurons. A subpopulation of Dcx-positive cells in the epileptic temporal cortex also coexpressed the mature neuronal marker, NeuN, suggesting that epilepsy may promote the generation of new neurons in the temporal cortex. This study has identified, for the first time, a novel population of Dcx-positive cells in the adult human temporal cortex that can be upregulated by epilepsy and thus, raises the possibility that these cells may have functional significance in the pathophysiology of epilepsy.

  9. 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

  10. 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

  11. Covert spatial attention is functionally intact in amblyopic human adults

    PubMed Central

    Roberts, Mariel; Cymerman, Rachel; Smith, R. Theodore; Kiorpes, Lynne; Carrasco, Marisa

    2016-01-01

    Certain abnormalities in behavioral performance and neural signaling have been attributed to a deficit of visual attention in amblyopia, a neurodevelopmental disorder characterized by a diverse array of visual deficits following abnormal binocular childhood experience. Critically, most have inferred attention's role in their task without explicitly manipulating and measuring its effects against a baseline condition. Here, we directly investigate whether human amblyopic adults benefit from covert spatial attention—the selective processing of visual information in the absence of eye movements—to the same degree as neurotypical observers. We manipulated both involuntary (Experiment 1) and voluntary (Experiment 2) attention during an orientation discrimination task for which the effects of covert spatial attention have been well established in neurotypical and special populations. In both experiments, attention significantly improved accuracy and decreased reaction times to a similar extent (a) between the eyes of the amblyopic adults and (b) between the amblyopes and their age- and gender-matched controls. Moreover, deployment of voluntary attention away from the target location significantly impaired task performance (Experiment 2). The magnitudes of the involuntary and voluntary attention benefits did not correlate with amblyopic depth or severity. Both groups of observers showed canonical performance fields (better performance along the horizontal than vertical meridian and at the lower than upper vertical meridian) and similar effects of attention across locations. Despite their characteristic low-level vision impairments, covert spatial attention remains functionally intact in human amblyopic adults. PMID:28033433

  12. The nutrition intervention improved adult human capital and economic productivity.

    PubMed

    Martorell, Reynaldo; Melgar, Paul; Maluccio, John A; Stein, Aryeh D; Rivera, Juan A

    2010-02-01

    This article reviews key findings about the long-term impact of a nutrition intervention carried out by the Institute of Nutrition of Central America and Panama from 1969 to 1977. Results from follow-up studies in 1988-89 and 2002-04 show substantial impact on adult human capital and economic productivity. The 1988-89 study showed that adult body size and work capacity increased for those provided improved nutrition through age 3 y, whereas the 2002-04 follow-up showed that schooling was increased for women and reading comprehension and intelligence increased in both men and women. Participants were 26-42 y of age at the time of the 2002-04 follow-up, facilitating the assessment of economic productivity. Wages of men increased by 46% in those provided with improved nutrition through age 2 y. Findings for cardiovascular disease risk factors were heterogeneous; however, they suggest that improved nutrition in early life is unlikely to increase cardiovascular disease risk later in life and may indeed lower risk. In conclusion, the substantial improvement in adult human capital and economic productivity resulting from the nutrition intervention provides a powerful argument for promoting improvements in nutrition in pregnant women and young children.

  13. 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

  14. Smelly primes – when olfactory primes do or do not work

    PubMed Central

    Smeets, M. A. M.; Dijksterhuis, G. B.

    2014-01-01

    In applied olfactory cognition the effects that olfactory stimulation can have on (human) behavior are investigated. To enable an efficient application of olfactory stimuli a model of how they may lead to a change in behavior is proposed. To this end we use the concept of olfactory priming. Olfactory priming may prompt a special view on priming as the olfactory sense has some unique properties which make odors special types of primes. Examples of such properties are the ability of odors to influence our behavior outside of awareness, to lead to strong affective evaluations, to evoke specific memories, and to associate easily and quickly to other environmental stimuli. Opportunities and limitations for using odors as primes are related to these properties, and alternative explanations for reported findings are offered. Implications for olfactory semantic, construal, behavior and goal priming are given based on a brief overview of the priming literature from social psychology and from olfactory perception science. We end by formulating recommendations and ideas for a future research agenda and applications for olfactory priming. PMID:24575071

  15. A direct anterior cingulate pathway to the primate primary olfactory cortex may control attention to olfaction

    PubMed Central

    García-Cabezas, Miguel Á.; Barbas, Helen

    2016-01-01

    Behavioral and functional studies in humans suggest that attention plays a key role in activating the primary olfactory cortex through an unknown circuit mechanism. We report that a novel pathway from the anterior cingulate cortex, an area which has a key role in attention, projects directly to the primary olfactory cortex in rhesus monkeys, innervating mostly the anterior olfactory nucleus. Axons from the anterior cingulate cortex formed synapses mostly with spines of putative excitatory pyramidal neurons and with a small proportion of a neurochemical class of inhibitory neurons that are thought to have disinhibitory effect on excitatory neurons. This novel pathway from the anterior cingulate is poised to exert a powerful excitatory effect on the anterior olfactory nucleus, which is a critical hub for odorant processing via extensive bilateral connections with primary olfactory cortices and the olfactory bulb. Acting on the anterior olfactory nucleus, the anterior cingulate may activate the entire primary olfactory cortex to mediate the process of rapid attention to olfactory stimuli. PMID:23797208

  16. 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.

  17. CCM2 expression during prenatal development and adult human neocortex.

    PubMed

    Tanriover, Gamze; Sozen, Berna; Gunel, Murat; Demir, Necdet

    2011-08-01

    Cerebral cavernous malformation (CCM) is one of the most common types of vascular malformations of the central nervous system, affecting nearly one in 200 people. CCM lesions are characterized by grossly dilated vascular channels lined by a single layer of endothelium. Genetic linkage analyses have mapped three CCM loci to CCM1, CCM2 and CCM3. All three causative genes have now been identified allowing new insights into CCM pathophysiology. We focused on the CCM2 protein that might take place in blood vessel formation; we report here the expression patterns of CCM2 in prenatal development and adult human neocortex by means of immunohistochemistry and Western blot analysis. CCM2 was obviously detected in vascular endothelium and neuroglial precursor cells during development and also observed in arterial endothelium, neurons, some of the glial cells in adult neocortex. The expression patterns suggest that it could be one of the arterial markers whether this is a cause or a consequence of an altered vascular identity. CCM2 might play a role during vasculogenesis and angiogenesis during human brain development. Furthermore, with this study, CCM2 have been described for the first time in developing human neocortex.

  18. 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

  19. Ontogeny of morningness-eveningness across the adult human lifespan

    NASA Astrophysics Data System (ADS)

    Randler, Christoph

    2016-02-01

    Sleep timing of humans can be classified alongside a continuum from early to late sleepers, with some people (larks) having an early activity, early bed, and rise times and others (owls) with a more nocturnally orientated activity. Only a few studies reported that morningness-eveningness changes significantly during the adult lifespan based on community samples. Here, I applied a different methodological approach to seek for evidence for the age-related changes in morningness-eveningness preferences by using a meta-data from all available studies. The new aspect of this cross-sectional approach is that only a few studies themselves address the age-related changes of the adult lifespan development, but that many studies are available that provide exactly the data needed. The studies came from 27 countries and included 36,939 participants. Age was highly significantly correlated with scores on the Composite Scale of Morningness ( r = 0.70). This relationship seems linear, because a linear regression explained nearly the same amount of variance compared to other models such as logarithmic, quadratic, or cubic models. The standard deviation of age correlated with the standard deviation of CSM scores ( r = 0.55), suggesting when there is much variance in age in a study; in turn, there is much variance in morningness. This meta-analytical approach shows that morningness-eveningness changes across the adult lifespan and that older age is related to higher morningness.

  20. Olfactory receptors are displayed on dog mature sperm cells

    PubMed Central

    1993-01-01

    Olfactory receptors constitute a huge family of structurally related G protein-coupled receptors, with up to a thousand members expected. We have shown previously that genes belonging to this family were expressed in the male germ line from both dog and human. The functional significance of this unexpected site of expression was further investigated in the present study. We demonstrate that a few dog genes representative of various subfamilies of olfactory receptors are expressed essentially in testis, with little or no expression in olfactory mucosa. Other randomly selected members of the family show the expected site of expression, restricted to the olfactory system. Antibodies were generated against the deduced amino acid sequence of the most abundantly expressed olfactory receptor gene in dog testis. The purified serum was able to detect the gene product (DTMT receptor) in late round and elongated spermatids, as well as in the cytoplasmic droplet that characterizes the maturation of dog sperm cells, and on the tail midpiece of mature spermatozoa. Western blotting further confirmed the presence of a 40-kD immunoreactive protein in the membrane of mature sperm cells. Altogether , these results demonstrate that the main expression site of a subset of the large olfactory receptor gene family is not olfactory mucosa but testis. This expression correlates with the presence of the corresponding protein during sperm cell maturation, and on mature sperm cells. The pattern of expression is consistent with a role as sensor for unidentified chemicals possibly involved in the control of mammalian sperm maturation, migration, and/or fertilization. PMID:8253843

  1. Using Insect Electroantennogram Sensors on Autonomous Robots for Olfactory Searches

    PubMed Central

    Martinez, Dominique; Arhidi, Lotfi; Demondion, Elodie; Masson, Jean-Baptiste; Lucas, Philippe

    2014-01-01

    Robots designed to track chemical leaks in hazardous industrial facilities1 or explosive traces in landmine fields2 face the same problem as insects foraging for food or searching for mates3: the olfactory search is constrained by the physics of turbulent transport4. The concentration landscape of wind borne odors is discontinuous and consists of sporadically located patches. A pre-requisite to olfactory search is that intermittent odor patches are detected. Because of its high speed and sensitivity5-6, the olfactory organ of insects provides a unique opportunity for detection. Insect antennae have been used in the past to detect not only sex pheromones7 but also chemicals that are relevant to humans, e.g., volatile compounds emanating from cancer cells8 or toxic and illicit substances9-11. We describe here a protocol for using insect antennae on autonomous robots and present a proof of concept for tracking odor plumes to their source. The global response of olfactory neurons is recorded in situ in the form of electroantennograms (EAGs). Our experimental design, based on a whole insect preparation, allows stable recordings within a working day. In comparison, EAGs on excised antennae have a lifetime of 2 hr. A custom hardware/software interface was developed between the EAG electrodes and a robot. The measurement system resolves individual odor patches up to 10 Hz, which exceeds the time scale of artificial chemical sensors12. The efficiency of EAG sensors for olfactory searches is further demonstrated in driving the robot toward a source of pheromone. By using identical olfactory stimuli and sensors as in real animals, our robotic platform provides a direct means for testing biological hypotheses about olfactory coding and search strategies13. It may also prove beneficial for detecting other odorants of interests by combining EAGs from different insect species in a bioelectronic nose configuration14 or using nanostructured gas sensors that mimic insect antennae15

  2. Using insect electroantennogram sensors on autonomous robots for olfactory searches.

    PubMed

    Martinez, Dominique; Arhidi, Lotfi; Demondion, Elodie; Masson, Jean-Baptiste; Lucas, Philippe

    2014-08-04

    Robots designed to track chemical leaks in hazardous industrial facilities or explosive traces in landmine fields face the same problem as insects foraging for food or searching for mates: the olfactory search is constrained by the physics of turbulent transport. The concentration landscape of wind borne odors is discontinuous and consists of sporadically located patches. A pre-requisite to olfactory search is that intermittent odor patches are detected. Because of its high speed and sensitivity, the olfactory organ of insects provides a unique opportunity for detection. Insect antennae have been used in the past to detect not only sex pheromones but also chemicals that are relevant to humans, e.g., volatile compounds emanating from cancer cells or toxic and illicit substances. We describe here a protocol for using insect antennae on autonomous robots and present a proof of concept for tracking odor plumes to their source. The global response of olfactory neurons is recorded in situ in the form of electroantennograms (EAGs). Our experimental design, based on a whole insect preparation, allows stable recordings within a working day. In comparison, EAGs on excised antennae have a lifetime of 2 hr. A custom hardware/software interface was developed between the EAG electrodes and a robot. The measurement system resolves individual odor patches up to 10 Hz, which exceeds the time scale of artificial chemical sensors. The efficiency of EAG sensors for olfactory searches is further demonstrated in driving the robot toward a source of pheromone. By using identical olfactory stimuli and sensors as in real animals, our robotic platform provides a direct means for testing biological hypotheses about olfactory coding and search strategies. It may also prove beneficial for detecting other odorants of interests by combining EAGs from different insect species in a bioelectronic nose configuration or using nanostructured gas sensors that mimic insect antennae.

  3. 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.

  4. 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

  5. Canine olfactory detection of malignant melanoma

    PubMed Central

    Campbell, Leon Frederick; Farmery, Luke; George, Susannah Mary Creighton; Farrant, Paul B J

    2013-01-01

    Our patient is a 75-year-old man who presented after his pet dog licked persistently at an asymptomatic lesion behind his right ear. Examination revealed a nodular lesion in the postauricular sulcus. Histology confirmed malignant melanoma, which was subsequently excised. Canine olfactory detection of human malignancy is a well-documented phenomenon. Advanced olfaction is hypothesised to explain canine detection of bladder, breast, colorectal, lung, ovarian, prostate and skin cancers. Further research in this area may facilitate the development of a highly accurate aid to diagnosis for many malignancies, including melanoma. PMID:24127369

  6. Distribution of Tight Junction Proteins in Adult Human Salivary Glands

    PubMed Central

    Maria, Ola M.; Kim, Jung-Wan Martin; Gerstenhaber, Jonathan A.; Baum, Bruce J.; Tran, Simon D.

    2008-01-01

    Tight junctions (TJs) are an essential structure of fluid-secreting cells, such as those in salivary glands. Three major families of integral membrane proteins have been identified as components of the TJ: claudins, occludin, and junctional adhesion molecules (JAMs), plus the cytosolic protein zonula occludens (ZO). We have been working to develop an orally implantable artificial salivary gland that would be suitable for treating patients lacking salivary parenchymal tissue. To date, little is known about the distribution of TJ proteins in adult human salivary cells and thus what key molecular components might be desirable for the cellular component of an artificial salivary gland device. Therefore, the aim of this study was to determine the distribution of TJ proteins in human salivary glands. Salivary gland samples were obtained from 10 patients. Frozen and formalin-fixed paraffin-embedded sections were stained using IHC methods. Claudin-1 was expressed in ductal, endothelial, and ∼25% of serous cells. Claudins-2, -3, and -4 and JAM-A were expressed in both ductal and acinar cells, whereas claudin-5 was expressed only in endothelial cells. Occludin and ZO-1 were expressed in acinar, ductal, and endothelial cells. These results provide new information on TJ proteins in two major human salivary glands and should serve as a reference for future studies to assess the presence of appropriate TJ proteins in a tissue-engineered human salivary gland. (J Histochem Cytochem 56:1093–1098, 2008) PMID:18765838

  7. Cortical Plasticity and Olfactory Function in Early Blindness.

    PubMed

    Araneda, Rodrigo; Renier, Laurent A; Rombaux, Philippe; Cuevas, Isabel; De Volder, Anne G

    2016-01-01

    Over the last decade, functional brain imaging has provided insight to the maturation processes and has helped elucidate the pathophysiological mechanisms involved in brain plasticity in the absence of vision. In case of congenital blindness, drastic changes occur within the deafferented "visual" cortex that starts receiving and processing non visual inputs, including olfactory stimuli. This functional reorganization of the occipital cortex gives rise to compensatory perceptual and cognitive mechanisms that help blind persons achieve perceptual tasks, leading to superior olfactory abilities in these subjects. This view receives support from psychophysical testing, volumetric measurements and functional brain imaging studies in humans, which are presented here.

  8. Cortical Plasticity and Olfactory Function in Early Blindness

    PubMed Central

    Araneda, Rodrigo; Renier, Laurent A.; Rombaux, Philippe; Cuevas, Isabel; De Volder, Anne G.

    2016-01-01

    Over the last decade, functional brain imaging has provided insight to the maturation processes and has helped elucidate the pathophysiological mechanisms involved in brain plasticity in the absence of vision. In case of congenital blindness, drastic changes occur within the deafferented “visual” cortex that starts receiving and processing non visual inputs, including olfactory stimuli. This functional reorganization of the occipital cortex gives rise to compensatory perceptual and cognitive mechanisms that help blind persons achieve perceptual tasks, leading to superior olfactory abilities in these subjects. This view receives support from psychophysical testing, volumetric measurements and functional brain imaging studies in humans, which are presented here. PMID:27625596

  9. Functional Specialization of Olfactory Glomeruli in a Moth

    NASA Astrophysics Data System (ADS)

    Hansson, Bill S.; Ljungberg, Hakan; Hallberg, Eric; Lofstedt, Christer

    1992-05-01

    The specific function of the glomerular structures present in the antennal lobes or olfactory bulbs of organisms ranging from insects to humans has been obscure because of limitations in neuronal marking methods. By tracing individual neurons in the moth Agrotis segetum, it was determined that physiologically distinct types of pheromone receptor neurons project axons to different regions of the macroglomerular complex (MGC). Each glomerulus making up the MGC has a specific functional identity, initially processing information about one specific pheromone component. This indicates that, at least through the first stage of synapses, olfactory information moves through labeled lines.

  10. Longer latency of sensory response to intravenous odor injection predicts olfactory neural disorder

    PubMed Central

    Kikuta, Shu; Matsumoto, Yu; Kuboki, Akihito; Nakayama, Tsuguhisa; Asaka, Daiya; Otori, Nobuyoshi; Kojima, Hiromi; Sakamoto, Takashi; Akinori, Kashio; Kanaya, Kaori; Ueha, Rumi; Kagoya, Ryoji; Nishijima, Hironobu; Toma-Hirano, Makiko; Kikkawa, Yayoi; Kondo, Kenji; Tsunoda, Koichi; Miyaji, Tempei; Yamaguchi, Takuhiro; Kataoka, Kazunori; Mori, Kensaku; Yamasoba, Tatsuya

    2016-01-01

    A near loss of smell may result from conductive and/or neural olfactory disorders. However, an olfactory test to selectively detect neural disorders has not been established. We investigated whether onset latency of sensory response to intravenous odor injection can detect neural disorders in humans and mice. We showed that longer preoperative onset latency of odor recognition to intravenous odor in patients with chronic rhinosinusitis predicted worse recovery of olfactory symptoms following sinus surgery. The onset latency of the olfactory sensory neuron (OSN) response to intravenous odor using synaptopHluorin signals from OSN axon terminals was delayed in mice with reduced numbers of OSNs (neural disorder) but not with increased mucus or blocked orthonasal pathways (conductive disorders). Moreover, the increase in onset latency correlated with the decrease in mature OSN numbers. Longer onset latency to intravenous odor injection is a useful biomarker for presence and severity of olfactory disorders with neural etiology. PMID:27734933

  11. Using Single Sensillum Recording to Detect Olfactory Neuron Responses of Bed Bugs to Semiochemicals.

    PubMed

    Liu, Feng; Liu, Nannan

    2016-01-18

    The insect olfactory system plays an important role in detecting semiochemicals in the environment. In particular, the antennal sensilla which house single or multiple neurons inside, are considered to make the major contribution in responding to the chemical stimuli. By directly recording action potential in the olfactory sensillum after exposure to stimuli, single sensillum recording (SSR) technique provides a powerful approach for investigating the neural responses of insects to chemical stimuli. For the bed bug, which is a notorious human parasite, multiple types of olfactory sensillum have been characterized. In this study, we demonstrated neural responses of bed bug olfactory sensilla to two chemical stimuli and the dose-dependent responses to one of them using the SSR method. This approach enables researchers to conduct early screening for individual chemical stimuli on the bed bug olfactory sensilla, which would provide valuable information for the development of new bed bug attractants or repellents and benefits the bed bug control efforts.

  12. The Evolution of Mammalian Olfactory Receptor Genes

    PubMed Central

    Issel-Tarver, L.; Rine, J.

    1997-01-01

    We performed a comparative study of four subfamilies of olfactory receptor genes first identified in the dog to assess changes in the gene family during mammalian evolution, and to begin linking the dog genetic map to that of humans. The human subfamilies were localized to chromosomes 7, 11, and 19. The two subfamilies that were tightly linked in the dog genome were also tightly linked in the human genome. The four subfamilies were compared in human (primate), horse (perissodactyl), and a variety of artiodactyls and carnivores. Some changes in gene number were detected, but overall subfamily size appeared to have been established before the divergence of these mammals 60-100 million years ago. PMID:9017400

  13. 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

  14. Neuropeptide Y in the adult and fetal human pineal gland.

    PubMed

    Møller, Morten; Phansuwan-Pujito, Pansiri; Badiu, Corin

    2014-01-01

    Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally.

  15. 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.

  16. 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

  17. Sex Determination of Adult Human Maxillary Sinuses on Panoramic Radiographs.

    PubMed

    Leao de Queiroz, Cristhiane; Terada, Andrea Sayuri Silveira Dias; Dezem, Thais Uenoyama; Gomes de Araújo, Lais; Galo, Rodrigo; Oliveira-Santos, Christiano; Alves da Silva, Ricardo Henrique

    2016-09-01

    The purpose of this study was to evaluate dimensions of adult human maxillary sinuses on panoramic radiographs and their possible application on the sex determination for forensic purposes. The sample comprised 64 database panoramic radiographs from individuals aged 20 years or older (32 male and 32 female subjects), with complete permanent dentition (or absence of third molars). One examiner measured the width and height of the right and left maxillary sinuses using the software Image J 1.47v (National Institutes of Health, Bethesda, USA). Measurements were repeated to calculate intra-observer agreement. Chi-Square test, Kappa, ANOVA and T-Student were used for results analysis for p≤ 0.05. Intra-observer agreement with correlation Kappa ranged between 0.38 and 0.96. For female subjects, the mean height and width of the left maxillary sinus were 28.7856mm and 44.6178mm, respectively. And right maxillary sinus was 27.7163mm for height and 45.1850mm for width. Male subjects were found to have the mean height and width of the left maxillary sinus 30.9981mm and 48.7753mm, respectively. And right maxillary sinus was 30.7403mm for height and 48.5753mm for width. There was a statistically significant difference in the height and width of maxillary sinuses between males and females. It can be concluded that maxillary sinuses height and width on panoramic radiographs can be used to determine the gender of adult human subjects.

  18. The adult human pubic symphysis: a systematic review

    PubMed Central

    Becker, Ines; Woodley, Stephanie J; Stringer, Mark D

    2010-01-01

    The pubic symphysis is a unique joint consisting of a fibrocartilaginous disc sandwiched between the articular surfaces of the pubic bones. It resists tensile, shearing and compressive forces and is capable of a small amount of movement under physiological conditions in most adults (up to 2 mm shift and 1° rotation). During pregnancy, circulating hormones such as relaxin induce resorption of the symphyseal margins and structural changes in the fibrocartilaginous disc, increasing symphyseal width and mobility. This systematic review of the English, German and French literature focuses on the normal anatomy of the adult human pubic symphysis. Although scientific studies of the joint have yielded useful descriptive data, comparison of results is hampered by imprecise methodology and/or poorly controlled studies. Several aspects of the anatomy of the pubic symphysis remain unknown or unclear: the precise attachments of surrounding ligaments and muscles; the arrangement of connective tissue fibres within the interpubic disc and the origin, structure and function of its associated interpubic cleft; the biomechanical consequences of sexual dimorphism; potential ethnic variations in morphology; and its precise innervation and blood supply. These deficiencies hinder our understanding of the normal form and function of the joint, which is particularly relevant when attempting to understand the mechanisms underlying pregnancy-related pubic symphyseal pain, a neglected and relatively common cause of pubic pain. A better understanding of the normal anatomy of the human pubic symphysis should improve our understanding of such problems and contribute to better treatments for patients suffering from symphyseal pain and dysfunction. PMID:20840351

  19. Sex Determination of Adult Human Maxillary Sinuses on Panoramic Radiographs

    PubMed Central

    Leao de Queiroz, Cristhiane; Terada, Andrea Sayuri Silveira Dias; Dezem, Thais Uenoyama; Gomes de Araújo, Lais; Galo, Rodrigo; Oliveira-Santos, Christiano

    2016-01-01

    Absract The purpose of this study was to evaluate dimensions of adult human maxillary sinuses on panoramic radiographs and their possible application on the sex determination for forensic purposes. The sample comprised 64 database panoramic radiographs from individuals aged 20 years or older (32 male and 32 female subjects), with complete permanent dentition (or absence of third molars). One examiner measured the width and height of the right and left maxillary sinuses using the software Image J 1.47v (National Institutes of Health, Bethesda, USA). Measurements were repeated to calculate intra-observer agreement. Chi-Square test, Kappa, ANOVA and T-Student were used for results analysis for p≤ 0.05. Intra-observer agreement with correlation Kappa ranged between 0.38 and 0.96. For female subjects, the mean height and width of the left maxillary sinus were 28.7856mm and 44.6178mm, respectively. And right maxillary sinus was 27.7163mm for height and 45.1850mm for width. Male subjects were found to have the mean height and width of the left maxillary sinus 30.9981mm and 48.7753mm, respectively. And right maxillary sinus was 30.7403mm for height and 48.5753mm for width. There was a statistically significant difference in the height and width of maxillary sinuses between males and females. It can be concluded that maxillary sinuses height and width on panoramic radiographs can be used to determine the gender of adult human subjects. PMID:27847394

  20. Mainstream cigarette smoke exposure alters cytochrome P4502G1 expression in F344 rat olfactory mucosa

    SciTech Connect

    Hotchkiss, J.A.; Nikula, K.J.; Lewis, J.L.; Finch, G.L.; Belinsky, S.A.; Dahl, A.R.

    1994-11-01

    Inhalation of mainstream cigarette smoke (MCS) by rats results in multifocal rhinitis, mucous hypersecretion, nasal epithelial hyperplasia and metaplasia, and focal olfactory mucosal atrophy. In humans, cigarette smoking causes long-term, dose-related alterations in olfactory function in both current and former smokers. An olfactory-specific cytochrome P450 has been identified in rabbits and rats. The presence of olfactory-specific P450s, as well as relatively high levels of other biotransformation enzymes, such as NADPH-cytochrome P450 reductase and UDP-glucuronosyl transferase, in the olfactory neuroepithelium suggest that these enzyme systems may play a role in olfaction. This hypothesis is strengthened by the observation that, in rats, the temporal gene activation of P4502G1 coincides with the postnatal increase in the sensitivity of olfactory response to odorants. The purpose of this investigation was to examine the effect of MCS exposure on P4502G1 protein expression.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. The Effect of Body Mass on Outdoor Adult Human Decomposition.

    PubMed

    Roberts, Lindsey G; Spencer, Jessica R; Dabbs, Gretchen R

    2017-02-23

    Forensic taphonomy explores factors impacting human decomposition. This study investigated the effect of body mass on the rate and pattern of adult human decomposition. Nine males and three females aged 49-95 years ranging in mass from 73 to 159 kg who were donated to the Complex for Forensic Anthropology Research between December 2012 and September 2015 were included in this study. Kelvin accumulated degree days (KADD) were used to assess the thermal energy required for subjects to reach several total body score (TBS) thresholds: early decomposition (TBS ≥6.0), TBS ≥12.5, advanced decomposition (TBS ≥19.0), TBS ≥23.0, and skeletonization (TBS ≥27.0). Results indicate no significant correlation between body mass and KADD at any TBS threshold. Body mass accounted for up to 24.0% of variation in decomposition rate depending on stage, and minor differences in decomposition pattern were observed. Body mass likely has a minimal impact on postmortem interval estimation.

  11. Adult human liver mesenchymal progenitor cells express phenylalanine hydroxylase.

    PubMed

    Baruteau, Julien; Nyabi, Omar; Najimi, Mustapha; Fauvart, Maarten; Sokal, Etienne

    2014-09-01

    Phenylketonuria (PKU) is one of the most prevalent inherited metabolic diseases and is accountable for a severe encephalopathy by progressive intoxication of the brain by phenylalanine. This results from an ineffective L-phenylalanine hydroxylase enzyme (PAH) due to a mutated phenylalanine hydroxylase (PAH) gene. Neonatal screening programs allow an early dietetic treatment with restrictive phenylalanine intake. This diet prevents most of the neuropsychological disabilities but remains challenging for lifelong compliance. Adult-derived human liver progenitor cells (ADHLPC) are a pool of precursors that can differentiate into hepatocytes. We aim to study PAH expression and PAH activity in a differenciated ADHLPC. ADHLPC were isolated from human hepatocyte primary culture of two different donors and differenciated under specific culture conditions. We demonstrated the high expression of PAH and a large increase of PAH activity in differenciated LPC. The age of the donor, the cellular viability after liver digestion and cryopreservation affects PAH activity. ADHLPC might therefore be considered as a suitable source for cell therapy in PKU.

  12. Ossified Ligamentum Longitudinale Anterius in Adult Human Dry Vertebrae

    PubMed Central

    Venumadhav, Nelluri; KS, Siddaraju

    2014-01-01

    Background: The ligamentum longitudinale anterius is a broad and strong band of fibrous tissue that runs along the anterior surfaces of the bodies of the vertebrae. Aim: The study was undertaken to evaluate the incidence of ossified ligamentum longitudinale anterius in adult dry human vertebra. Materials and Methods: This study was carried out on 95 sets of dry human vertebral columns irrespective of age and sex at Mayo Institute of Medical Sciences- Barabanki,-UP, Melaka Manipal Medical College-Manipal University and Department of Anatomy, KMCT Medical College, Manassery- Calicut, India. All the sets of vertebral columns were macroscopically inspected for the ossified ligamentum longitudinale anterius. Results: It was observed that out of 95 sets of vertebral columns, 27 (28.42%) vertebral columns showed ossification. Out of 27 vertebral columns, 17 (17.89%) vertebral columns showed segmental type of ossification, 2 (2.11%) vertebral columns showed continuous type of ossification and 8 (8.42%) vertebral columns showed mixed type of ossification at different vertebral level. Conclusion: Such type of ossification will affect the biomechanics of the spine and may result in stiff neck, low back pain, dysphagia, odynophagia, compression of the brachial plexus, aphonia, immobility or mucosal thickening of larynx. Hence, knowledge of such abnormalities should be kept in mind to minimise serious complications in any surgical intervention or investigative procedures in the region. PMID:25302180

  13. A biokinetic model for systemic technetium in adult humans

    SciTech Connect

    Leggett, Richard Wayne; Giussani, Augusto

    2015-04-10

    The International Commission on Radiological Protection (ICRP) currently is updating its biokinetic and dosimetric models for internally deposited radionuclides. Technetium (Tc), the lightest element that exists only in radioactive form, has two important isotopes from the standpoint of potential risk to humans: the long-lived isotope 99Tm(T1/2=2.1x105 y) is present in high concentration in nuclear waste, and the short-lived isotope 99mTc (T1/2=6.02 h) is the most commonly used radionuclide in diagnostic nuclear medicine. This paper reviews data on the biological behavior of technetium and proposes a biokinetic model for systemic technetium in the adult human body for use in radiation protection. Compared with the ICRP s current occupational model for systemic technetium, the proposed model provides a more realistic description of the paths of movement of technetium in the body; provides greater consistency with experimental and medical data; and, for most radiosensitive organs, yields substantially different estimates of cumulative activity (total radioactive decays within the organ) following uptake of 99Tm or 99mTc to blood.

  14. A biokinetic model for systemic technetium in adult humans

    DOE PAGES

    Leggett, Richard Wayne; Giussani, Augusto

    2015-04-10

    The International Commission on Radiological Protection (ICRP) currently is updating its biokinetic and dosimetric models for internally deposited radionuclides. Technetium (Tc), the lightest element that exists only in radioactive form, has two important isotopes from the standpoint of potential risk to humans: the long-lived isotope 99Tm(T1/2=2.1x105 y) is present in high concentration in nuclear waste, and the short-lived isotope 99mTc (T1/2=6.02 h) is the most commonly used radionuclide in diagnostic nuclear medicine. This paper reviews data on the biological behavior of technetium and proposes a biokinetic model for systemic technetium in the adult human body for use in radiation protection.more » Compared with the ICRP s current occupational model for systemic technetium, the proposed model provides a more realistic description of the paths of movement of technetium in the body; provides greater consistency with experimental and medical data; and, for most radiosensitive organs, yields substantially different estimates of cumulative activity (total radioactive decays within the organ) following uptake of 99Tm or 99mTc to blood.« less

  15. Comprehensive cellular‐resolution atlas of the adult human brain

    PubMed Central

    Royall, Joshua J.; Sunkin, Susan M.; Ng, Lydia; Facer, Benjamin A.C.; Lesnar, Phil; Guillozet‐Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A.; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A.; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L.; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A.; Koch, Christof; Phillips, John W.; Sestan, Nenad; Wohnoutka, Paul; Zielke, H. Ronald; Hohmann, John G.; Jones, Allan R.; Bernard, Amy; Hawrylycz, Michael J.; Hof, Patrick R.; Fischl, Bruce

    2016-01-01

    ABSTRACT Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole‐brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high‐resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion‐weighted imaging (DWI), and 1,356 large‐format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto‐ and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127–3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:27418273

  16. Olfactory Ensheathing Cells Rescue Optic Nerve Fibers in a Rat Glaucoma Model

    PubMed Central

    Dai, Chao; Khaw, Peng T.; Yin, Zheng Qin; Li, Daqing; Raisman, Geoffrey; Li, Ying

    2012-01-01

    Purpose: To determine if transplantation of olfactory ensheathing cells (OECs) can reduce loss of optic nerve axons after raised intraocular pressure (IOP) in the rat. Methods: OECs cultured from the adult olfactory mucosa were transplanted into the region of the optic disc. The IOP was raised by injection of magnetic microspheres into the anterior chamber. Results: At 4 weeks after raising the IOP, the transplanted OECs had migrated into the dorsal area of the optic nerve head (ONH) where they surrounded the optic nerve fibers with a non-myelinated ensheathment. The mean amount of damage to the ONH astrocytic area in rats was 51.0% compared with 85.8% in those without OEC transplants (P < 0.02) and the mean loss of axons in the optic nerve was 51.0% compared with 80.3% in the absence of OECs (P < 0.01). Conclusions: OECs transplanted into the region of the ONH of the rat can reduce the loss of axons and the damage to ONH astrocytes caused by raised IOP. Translational Relevance: Confirmation of these preliminary experimental data, further understanding of possible mechanisms of axonal protection by OECs, and the longer-term time course of protection could provide a basis for future human clinical trials of autografted OECs, which would be available from autologous nasal epithelial biopsies. PMID:24049703

  17. High-throughput Analysis of Mammalian Olfactory Receptors: Measurement of Receptor Activation via Luciferase Activity

    PubMed Central

    Trimmer, Casey; Snyder, Lindsey L.; Mainland, Joel D.

    2014-01-01

    Odorants create unique and overlapping patterns of olfactory receptor activation, allowing a family of approximately 1,000 murine and 400 human receptors to recognize thousands of odorants. Odorant ligands have been published for fewer than 6% of human receptors1-11. This lack of data is due in part to difficulties functionally expressing these receptors in heterologous systems. Here, we describe a method for expressing the majority of the olfactory receptor family in Hana3A cells, followed by high-throughput assessment of olfactory receptor activation using a luciferase reporter assay. This assay can be used to (1) screen panels of odorants against panels of olfactory receptors; (2) confirm odorant/receptor interaction via dose response curves; and (3) compare receptor activation levels among receptor variants. In our sample data, 328 olfactory receptors were screened against 26 odorants. Odorant/receptor pairs with varying response scores were selected and tested in dose response. These data indicate that a screen is an effective method to enrich for odorant/receptor pairs that will pass a dose response experiment, i.e. receptors that have a bona fide response to an odorant. Therefore, this high-throughput luciferase assay is an effective method to characterize olfactory receptors—an essential step toward a model of odor coding in the mammalian olfactory system. PMID:24961834

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. Ecological adaptation determines functional mammalian olfactory subgenomes

    PubMed Central

    Hayden, Sara; Bekaert, Michaël; Crider, Tess A.; Mariani, Stefano; Murphy, William J.; Teeling, Emma C.

    2010-01-01

    The ability to smell is governed by the largest gene family in mammalian genomes, the olfactory receptor (OR) genes. Although these genes are well annotated in the finished human and mouse genomes, we still do not understand which receptors bind specific odorants or how they fully function. Previous comparative studies have been taxonomically limited and mostly focused on the percentage of OR pseudogenes within species. No study has investigated the adaptive changes of functional OR gene families across phylogenetically and ecologically diverse mammals. To determine the extent to which OR gene repertoires have been influenced by habitat, sensory specialization, and other ecological traits, to better understand the functional importance of specific OR gene families and thus the odorants they bind, we compared the functional OR gene repertoires from 50 mammalian genomes. We amplified more than 2000 OR genes in aquatic, semi-aquatic, and flying mammals and coupled these data with 48,000 OR genes from mostly terrestrial mammals, extracted from genomic projects. Phylogenomic, Bayesian assignment, and principle component analyses partitioned species by ecotype (aquatic, semi-aquatic, terrestrial, flying) rather than phylogenetic relatedness, and identified OR families important for each habitat. Functional OR gene repertoires were reduced independently in the multiple origins of aquatic mammals and were significantly divergent in bats. We reject recent neutralist views of olfactory subgenome evolution and correlate specific OR gene families with physiological requirements, a preliminary step toward unraveling the relationship between specific odors and respective OR gene families. PMID:19952139

  5. Features of hand-foot crawling behavior in human adults.

    PubMed

    Maclellan, M J; Ivanenko, Y P; Cappellini, G; Sylos Labini, F; Lacquaniti, F

    2012-01-01

    Interlimb coordination of crawling kinematics in humans shares features with other primates and nonprimate quadrupeds, and it has been suggested that this is due to a similar organization of the locomotor pattern generators (CPGs). To extend the previous findings and to further explore the neural control of bipedal vs. quadrupedal locomotion, we used a crawling paradigm in which healthy adults crawled on their hands and feet at different speeds and at different surface inclinations (13°, 27°, and 35°). Ground reaction forces, limb kinematics, and electromyographic (EMG) activity from 26 upper and lower limb muscles on the right side of the body were collected. The EMG activity was mapped onto the spinal cord in approximate rostrocaudal locations of the motoneuron pools to characterize the general features of cervical and lumbosacral spinal cord activation. The spatiotemporal pattern of spinal cord activity significantly differed between quadrupedal and bipedal gaits. In addition, participants exhibited a large range of kinematic coordination styles (diagonal vs. lateral patterns), which is in contrast to the stereotypical kinematics of upright bipedal walking, suggesting flexible coupling of cervical and lumbosacral pattern generators. Results showed strikingly dissimilar directional horizontal forces for the arms and legs, considerably retracted average leg orientation, and substantially smaller sacral vs. lumbar motoneuron activity compared with quadrupedal gait in animals. A gradual transition to a more vertical body orientation (increasing the inclination of the treadmill) led to the appearance of more prominent sacral activity (related to activation of ankle plantar flexors), typical of bipedal walking. The findings highlight the reorganization and adaptation of CPG networks involved in the control of quadrupedal human locomotion and a high specialization of the musculoskeletal apparatus to specific gaits.

  6. Metric analysis of basal sphenoid angle in adult human skulls

    PubMed Central

    Netto, Dante Simionato; Nascimento, Sergio Ricardo Rios; Ruiz, Cristiane Regina

    2014-01-01

    Objective To analyze the variations in the angle basal sphenoid skulls of adult humans and their relationship to sex, age, ethnicity and cranial index. Methods The angles were measured in 160 skulls belonging to the Museum of the Universidade Federal de São Paulo Department of Morphology. We use two flexible rules and a goniometer, having as reference points for the first rule the posterior end of the ethmoidal crest and dorsum of the sella turcica, and for the second rule the anterior margin of the foramen magnum and clivus, measuring the angle at the intersection of two. Results The average angle was 115.41°, with no statistical correlation between the value of the angle and sex or age. A statistical correlation was noted between the value of the angle and ethnicity, and between the angle and the horizontal cranial index. Conclusions The distribution of the angle basal sphenoid was the same in sex, and there was correlation between the angle and ethnicity, being the proportion of non-white individuals with an angle >125° significantly higher than that of whites with an angle >125°. There was correlation between the angle and the cranial index, because skulls with higher cranial index tend to have higher basiesfenoidal angle too. PMID:25295452

  7. Olfactory mucosa for transplant-mediated repair: a complex tissue for a complex injury?

    PubMed

    Lindsay, Susan L; Riddell, John S; Barnett, Susan C

    2010-01-15

    Damage to the brain and spinal cord leads to permanent functional disability because of the very limited capacity of the central nervous system (CNS) for repair. Transplantation of cells into regions of CNS damage represents one approach to enhancing this repair. At present, the ideal cell type for transplant-mediated repair has not been identified but autologous transplantation would be advantageous. Olfactory tissue, in part because of its capacity for regeneration, has emerged as a promising source of cells and several clinical centers are using olfactory cells or tissues in the treatment of CNS damage. Until now, the olfactory ensheathing cell, a specialized glial cell of the olfactory system has been the main focus of attention. Transplants of this cell have been shown to have a neuroprotective function, support axonal regeneration, and remyelinate demyelinated axons. However, the olfactory mucosa is a heterogeneous tissue, composed of a variety of cells supporting both its normal function and its regenerative capacity. It is therefore possible that it contains several cell types that could participate in CNS repair including putative stem cells as well as glia. Here we review the cellular composition of the olfactory tissue and the evidence that equivalent cell types exist in both rodent and human olfactory mucosa suggesting that it is potentially a rich source of autologous cells for transplant-mediated repair of the CNS.

  8. Dynamic cortical lateralization during olfactory discrimination learning

    PubMed Central

    Cohen, Yaniv; Putrino, David; Wilson, Donald A

    2015-01-01

    Key points Odour discrimination and memory involve changes in the primary olfactory (piriform) cortex. The results obtained in the present study suggest that there is an asymmetry in piriform cortical change, with learning-related changes in cortical oscillations emerging with different time courses over the course of multiday training in the left and right piriform cortices in rats. There is an initial decrease in coherence between the left and right piriform cortices during the early stages of the odour discrimination task, which recovers as the animals approach criterion performance. This decreased coherence is expressed when the animals are performing the task relative to when they are in their home cage. The results suggest a transient cortical asymmetry during learning and raise new questions about the functions and mechanisms of cerebral lateralization. Abstract Bilateral cortical circuits are not necessarily symmetrical. Asymmetry, or cerebral lateralization, allows functional specialization of bilateral brain regions and has been described in humans for such diverse functions as perception, memory and emotion. There is also evidence for asymmetry in the human olfactory system, although evidence in non-human animal models is lacking. In the present study, we took advantage of the known changes in olfactory cortical local field potentials that occur over the course of odour discrimination training to test for functional asymmetry in piriform cortical activity during learning. Both right and left piriform cortex local field potential activities were recorded. The results obtained demonstrate a robust interhemispheric asymmetry in anterior piriform cortex activity that emerges during specific stages of odour discrimination learning, with a transient bias toward the left hemisphere. This asymmetry is not apparent during error trials. Furthermore, functional connectivity (coherence) between the bilateral anterior piriform cortices is learning- and context

  9. 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

  10. 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

  11. 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.

  12. 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

  13. Immunoreactivity of thymosin beta 4 in human foetal and adult genitourinary tract

    PubMed Central

    Nemolato, S.; Cabras, T.; Fanari, M.U.; Cau, F.; Fanni, D.; Gerosa, C.; Manconi, B.; Messana, I.; Castagnola, M.; Faa, G.

    2010-01-01

    Thymosin beta 4 (Tβ4) is a member of the beta-thymosins family, a family of peptides playing essential roles in many cellular functions. Our recent studies suggested Tβ4 plays a key role in the development of human salivary glands and the gastrointestinal tract. The aim of this study was to analyse the presence of Tβ4 in the human adult and foetal genitourinary tract. Immunolocalization of Tβ4 was studied in autoptic samples of kidney, bladder, uterus, ovary, testicle and prostate obtained from four human foetuses and four adults. Presence of the peptide was observed in cells of different origin: in surface epithelium, in gland epithelial cells and in the interstitial cells. Tβ4 was mainly found in adult and foetal bladder in the transitional epithelial cells; in the adult endometrium, glands and stromal cells were immunoreactive for the peptide; Tβ4 was mainly localized in the glands of foetal prostate while, in the adults a weak Tβ4 reactivity was restricted to the stroma. In adult and foetal kidney, Tβ4 reactivity was restricted to ducts and tubules with completely spared glomeruli; a weak positivity was observed in adult and foetal oocytes; immunoreactivity was mainly localized in the interstitial cells of foetal and adult testis. In this study, we confirm that Tβ4 could play a relevant role during human development, even in the genitourinary tract, and reveal that immunoreactivity for this peptide may change during postnatal and adult life. PMID:21263742

  14. Transcriptional profiling of adult neural stem-like cells from the human brain.

    PubMed

    Sandberg, Cecilie Jonsgar; Vik-Mo, Einar O; Behnan, Jinan; Helseth, Eirik; Langmoen, Iver A

    2014-01-01

    There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33-60). Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate). We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6), foetal human neural stem cells (n = 1) and human brain tissues (n = 12). The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular fate.

  15. Hyperoxia Induces Inflammation and Cytotoxicity in Human Adult Cardiac Myocytes.

    PubMed

    Hafner, Christina; Wu, Jing; Tiboldi, Akos; Hess, Moritz; Mitulovic, Goran; Kaun, Christoph; Krychtiuk, Konstantin Alexander; Wojta, Johann; Ullrich, Roman; Tretter, Eva Verena; Markstaller, Klaus; Klein, Klaus Ulrich

    2017-04-01

    Supplemental oxygen (O2) is used as adjunct therapy in anesthesia, emergency, and intensive care medicine. We hypothesized that excessive O2 levels (hyperoxia) can directly injure human adult cardiac myocytes (HACMs). HACMs obtained from the explanted hearts of transplantation patients were exposed to constant hyperoxia (95% O2), intermittent hyperoxia (alternating 10 min exposures to 5% and 95% O2), constant normoxia (21% O2), or constant mild hypoxia (5% O2) using a bioreactor. Changes in cell morphology, viability as assessed by lactate dehydrogenase (LDH) release and trypan blue (TB) staining, and secretion of vascular endothelial growth factor (VEGF), macrophage migration inhibitory factor (MIF), and various pro-inflammatory cytokines (interleukin, IL; chemokine C-X-C motif ligand, CXC; granulocyte-colony stimulating factor, G-CSF; intercellular adhesion molecule, ICAM; chemokine C-C motif ligand, CCL) were compared among treatment groups at baseline (0 h) and after 8, 24, and 72 h of treatment. Changes in HACM protein expression were determined by quantitative proteomic analysis after 48 h of exposure. Compared with constant normoxia and mild hypoxia, constant hyperoxia resulted in a higher TB-positive cell count, greater release of LDH, and elevated secretion of VEGF, MIF, IL-1β, IL-6, IL-8, CXCL-1, CXCL-10, G-CSF, ICAM-1, CCL-3, and CCL-5. Cellular inflammation and cytotoxicity gradually increased and was highest after 72 h of constant and intermittent hyperoxia. Quantitative proteomic analysis revealed that hypoxic and hyperoxic O2 exposure differently altered the expression levels of proteins involved in cell-cycle regulation, energy metabolism, and cell signaling. In conclusion, constant and intermittent hyperoxia induced inflammation and cytotoxicity in HACMs. Cell injury occurred earliest and was greatest after constant hyperoxia, but even relatively brief repeating hyperoxic episodes induced a substantial inflammatory response.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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…

  1. 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.

  2. 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

  3. 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

  4. Brain stem auditory evoked responses in human infants and adults

    NASA Technical Reports Server (NTRS)

    Hecox, K.; Galambos, R.

    1974-01-01

    Brain stem evoked potentials were recorded by conventional scalp electrodes in infants (3 weeks to 3 years of age) and adults. The latency of one of the major response components (wave V) is shown to be a function both of click intensity and the age of the subject; this latency at a given signal strength shortens postnatally to reach the adult value (about 6 msec) by 12 to 18 months of age. The demonstrated reliability and limited variability of these brain stem electrophysiological responses provide the basis for an optimistic estimate of their usefulness as an objective method for assessing hearing in infants and adults.

  5. Adult Continuing Education and Human Resource Development: Present Competitors, Potential Partners

    ERIC Educational Resources Information Center

    Smith, Douglas H.

    2006-01-01

    Adult Continuing Education (ACE) and Human Resource Development (HRD) have grown tremendously in the last quarter century. ACE experienced tremendous growth in the 60s and 70s, with over 17 million attending colleges and universities, and local school and community adult education programs by the end of the 1970s. More ACE programs were started…

  6. Field Survey Measures of Olfaction: The Olfactory Function Field Exam (OFFE)

    PubMed Central

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

    2016-01-01

    Population-based field research on human olfaction has been limited by a lack of feasible assessment tools. Previous olfactory survey research has measured only odor identification, with no research being done on odor detection (i.e., a person's sensitivity to detect a particular odor). Laboratory studies suggest that deficits in both aspects of olfactory function may be related to physical health, mental health and cognition, social function, including overall quality of life, and even mortality. However, field studies are needed to validate and extend these findings in large representative samples. Here we describe the olfactory function field exam, an instrument that can be deployed in field environments by lay interviewers to evaluate both odor identification and odor detection rapidly, practically, and accurately. Use of this new survey tool in future field-based population health studies will elucidate the impact of olfactory function on a myriad of health and social conditions. PMID:27226782

  7. An olfactory cocktail party: figure-ground segregation of odorants in rodents.

    PubMed

    Rokni, Dan; Hemmelder, Vivian; Kapoor, Vikrant; Murthy, Venkatesh N

    2014-09-01

    In odorant-rich environments, animals must be able to detect specific odorants of interest against variable backgrounds. However, studies have found that both humans and rodents are poor at analyzing the components of odorant mixtures, suggesting that olfaction is a synthetic sense in which mixtures are perceived holistically. We found that mice could be easily trained to detect target odorants embedded in unpredictable and variable mixtures. To relate the behavioral performance to neural representation, we imaged the responses of olfactory bulb glomeruli to individual odors in mice expressing the Ca(2+) indicator GCaMP3 in olfactory receptor neurons. The difficulty of segregating the target from the background depended strongly on the extent of overlap between the glomerular responses to target and background odors. Our study indicates that the olfactory system has powerful analytic abilities that are constrained by the limits of combinatorial neural representation of odorants at the level of the olfactory receptors.

  8. Behavioral and magnetoencephalographic correlates of plasticity in the adult human brain

    PubMed Central

    Ramachandran, V. S.

    1993-01-01

    Recent behavioral and physiological evidence suggests that even brief sensory deprivation can lead to the rapid emergence of new and functionally effective neural connections in the adult human brain. Images Fig. 2 PMID:8248123

  9. Mechanism of olfactory masking in the sensory cilia

    PubMed Central

    Ishida, Hirohiko; Hikichi, Satoshi; Kurahashi, Takashi

    2009-01-01

    Olfactory masking has been used to erase the unpleasant sensation in human cultures for a long period of history. Here, we show a positive correlation between the human masking and the odorant suppression of the transduction current through the cyclic nucleotide–gated (CNG) and Ca2+-activated Cl− (Cl(Ca)) channels. Channels in the olfactory cilia were activated with the cytoplasmic photolysis of caged compounds, and their sensitiveness to odorant suppression was measured with the whole cell patch clamp. When 16 different types of chemicals were applied to cells, cyclic AMP (cAMP)-induced responses (a mixture of CNG and Cl(Ca) currents) were suppressed widely with these substances, but with different sensitivities. Using the same chemicals, in parallel, we measured human olfactory masking with 6-rate scoring tests and saw a correlation coefficient of 0.81 with the channel block. Ringer's solution that was just preexposed to the odorant-containing air affected the cAMP-induced current of the single cell, suggesting that odorant suppression occurs after the evaporation and air/water partition of the odorant chemicals at the olfactory mucus. To investigate the contribution of Cl(Ca), the current was exclusively activated by using the ultraviolet photolysis of caged Ca, DM-nitrophen. With chemical stimuli, it was confirmed that Cl(Ca) channels were less sensitive to the odorant suppression. It is interpreted, however, that in the natural odorant response the Cl(Ca) is affected by the reduction of Ca2+ influx through the CNG channels as a secondary effect. Because the signal transmission between CNG and Cl(Ca) channels includes nonlinear signal-boosting process, CNG channel blockage leads to an amplified reduction in the net current. In addition, we mapped the distribution of the Cl(Ca) channel in living olfactory single cilium using a submicron local [Ca2+]i elevation with the laser photolysis. Cl(Ca) channels are expressed broadly along the cilia. We conclude that

  10. Newborn human skin fibroblasts senesce in vitro without acquiring adult growth factor requirements

    SciTech Connect

    Wharton, W.

    1984-01-01

    Cultures of human fibroblasts were prepared from chest skin obtained either from newborns (less than 3 months old) or adults (more than 35 years old) and maintained in vitro until they senesced. Adult cells grew logarithmically in medium supplemented with whole blood serum but not with platelet-poor plasma. Early passage cells obtained from newborns grew equally well in either plasma- or serum-supplemented medium. The difference in growth factor requirements between adult and newborn cells persisted through the lifespan of the cells; i.e., newborn cells did not develop adult hormonal requirements when maintained in culture. Thus, in vitro cellular aging can be distinguished from some types of differentiation.

  11. SNP genotypes of olfactory receptor genes associated with olfactory ability in German Shepherd dogs.

    PubMed

    Yang, M; Geng, G-J; Zhang, W; Cui, L; Zhang, H-X; Zheng, J-L

    2016-04-01

    To find out the relationship between SNP genotypes of canine olfactory receptor genes and olfactory ability, 28 males and 20 females from German Shepherd dogs in police service were scored by odor detection tests and analyzed using the Beckman GenomeLab SNPstream. The representative 22 SNP loci from the exonic regions of 12 olfactory receptor genes were investigated, and three kinds of odor (human, ice drug and trinitrotoluene) were detected. The results showed that the SNP genotypes at the OR10H1-like:c.632C>T, OR10H1-like:c.770A>T, OR2K2-like:c.518G>A, OR4C11-like:c.511T>G and OR4C11-like:c.692G>A loci had a statistically significant effect on the scenting abilities (P < 0.001). The kind of odor influenced the performances of the dogs (P < 0.001). In addition, there were interactions between genotype and the kind of odor at the following loci: OR10H1-like:c.632C>T, OR10H1-like:c.770A>T, OR4C11-like:c.511T>G and OR4C11-like:c.692G>A (P < 0.001). The dogs with genotype CC at the OR10H1-like:c.632C>T, genotype AA at the OR10H1-like:c.770A>T, genotype TT at the OR4C11-like:c.511T>G and genotype GG at the OR4C11-like:c.692G>A loci did better at detecting the ice drug. We concluded that there was linkage between certain SNP genotypes and the olfactory ability of dogs and that SNP genotypes might be useful in determining dogs' scenting potential.

  12. 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

  13. Investigation of genes important in neurodevelopment disorders in adult human brain.

    PubMed

    Maussion, Gilles; Diallo, Alpha B; Gigek, Carolina O; Chen, Elizabeth S; Crapper, Liam; Théroux, Jean-Francois; Chen, Gary G; Vasuta, Cristina; Ernst, Carl

    2015-10-01

    Several neurodevelopmental disorders (NDDs) are caused by mutations in genes expressed in fetal brain, but little is known about these same genes in adult human brain. Here, we test the hypothesis that genes associated with NDDs continue to have a role in adult human brain to explore the idea that NDD symptoms may be partially a result of their adult function rather than just their neurodevelopmental function. To demonstrate adult brain function, we performed expression analyses and ChIPseq in human neural stem cell(NSC) lines at different developmental stages and adult human brain, targeting two genes associated with NDDs, SATB2 and EHMT1, and the WNT signaling gene TCF7L2, which has not been associated with NDDs. Analysis of DNA interaction sites in neural stem cells reveals high (40-50 %) overlap between proliferating and differentiating cells for each gene in temporal space. Studies in adult brain demonstrate that consensus sites are similar to NSCs but occur at different genomic locations. We also performed expression analyses using BrainSpan data for NDD-associated genes SATB2, EHMT1, FMR1, MECP2, MBD5, CTNND2, RAI1, CHD8, GRIN2A, GRIN2B, TCF4, SCN2A, and DYRK1A and find high expression of these genes in adult brain, at least comparable to developing human brain, confirming that genes associated with NDDs likely have a role in adult tissue. Adult function of genes associated with NDDs might be important in clinical disease presentation and may be suitable targets for therapeutic intervention.

  14. Cytoarchitecture of the Lateral Ganglionic Eminence and Rostral Extension of the Lateral Ventricle in the Human Fetal Brain

    PubMed Central

    Guerrero-Cázares, Hugo; Gonzalez-Perez, Oscar; Soriano-Navarro, Mario; Zamora-Berridi, Grettel; García-Verdugo, José Manuel; Quinoñes-Hinojosa, Alfredo

    2013-01-01

    The fetal development of the anterior subventricular zone (SVZ) involves the transformation of radial glia into neural stem cells, in addition to the migration of neuroblasts from the SVZ towards different regions in the brain. In adult rodents this migration from the anterior SVZ is restricted to the olfactory bulb following a rostral migratory stream (RMS) formed by chains of migratory neuroblasts. Similar to rodents, an RMS has been suggested in the adult human brain, where the SVZ remains as an active proliferative region. Nevertheless, a human fetal RMS has not been described and the presence of migratory neuroblasts in the adult remains controversial. Here we describe the cytoarchitecture of the human SVZ at the lateral ganglionic eminence late in the second trimester of development (23–24 weeks postconception). Cell organization in this region is heterogeneous along the ventricular wall, with GFAP-positive cells aligned to the ventricle. These cells coexpress markers for radial glia like GFAPδ, nestin, and vimentin. We also show the presence of abundant migratory neuroblasts in the anterior horn SVZ forming structures here denominated cell throngs. Interestingly, a ventral extension of the lateral ventricle suggests the presence of a putative RMS. Nevertheless, in the olfactory bulb neuroblast throngs or chain-like structures were not observed. The lack of these structures closer to the olfactory bulb could indicate a destination for the migratory neuroblasts outside the olfactory bulb in the human brain. PMID:21344407

  15. "Adult Education Is about Human Being in All Its Aspects"

    ERIC Educational Resources Information Center

    Stanistreet, Paul

    2011-01-01

    Derek Legge, who celebrated his 95th birthday at the end of last month, is one of the most dedicated and influential of the largely unsung heroes of the adult education movement in Britain. As modesty is one of the many qualities with which his friends and colleagues credit him, he is certain to shrink from the description, but there is little…

  16. The Human Function Compunction: Teleological Explanation in Adults

    ERIC Educational Resources Information Center

    Kelemen, Deborah; Rosset, Evelyn

    2009-01-01

    Research has found that children possess a broad bias in favor of teleological--or purpose-based--explanations of natural phenomena. The current two experiments explored whether adults implicitly possess a similar bias. In Study 1, undergraduates judged a series of statements as "good" (i.e., correct) or "bad" (i.e., incorrect) explanations for…

  17. Human Capital Development: Reforms for Adult and Community Education

    ERIC Educational Resources Information Center

    Choy, Sarojni; Haukka, Sandra

    2007-01-01

    The adult and community education (ACE) sector is consistently responsive to changing community needs and government priorities. It is this particular function that has drawn ACE into the lifelong learning debate as one model for sustaining communities. The responsiveness of ACE means that the sector and its programs continue to make valuable…

  18. 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.

  19. Antennal olfactory sensilla responses to insect chemical repellents in the common bed bug, Cimex lectularius.

    PubMed

    Liu, Feng; Haynes, Kenneth F; Appel, Arthur G; Liu, Nannan

    2014-06-01

    Populations of the common bed bug Cimex lectularius (Hemiptera; Cimicidae), a temporary ectoparasite on both humans and animals, have surged in many developed countries. Similar to other haematophagous arthropods, C. lectularius relies on its olfactory system to detect semiochemicals in the environment, including both attractants and repellents. To elucidate the olfactory responses of the common bed bug to commonly used insect chemical repellents, particularly haematophagous repellents, we investigated the neuronal responses of individual olfactory sensilla in C. lectularius' antennae to 52 insect chemical repellents, both synthetic and botanic. Different types of sensilla displayed highly distinctive response profiles. While C sensilla did not respond to any of the insect chemical repellents, Dγ sensilla proved to be the most sensitive in response to terpene-derived insect chemical repellents. Different chemical repellents elicited neuronal responses with differing temporal characteristics, and the responses of the olfactory sensilla to the insect chemical repellents were dose-dependent, with an olfactory response to the terpene-derived chemical repellent, but not to the non-terpene-derived chemical repellents. Overall, this study furnishes a comprehensive map of the olfactory response of bed bugs to commonly used insect chemical repellents, providing useful information for those developing new agents (attractants or repellents) for bed bug control.

  20. An Inventory of Skills and Attitudes Necessary for a Career in Human Services/Adult Care.

    ERIC Educational Resources Information Center

    Broadbent, William

    This document is an inventory of skills identified as necessary by professionals in the human services field specializing in adult care. It is intended as a mechanism whereby educators can compare that which they teach against what the human services industry feels is relevant. Introductory material discusses the process of the occupational…

  1. 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.

  2. 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.

  3. 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...

  4. 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...

  5. 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

  6. 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.

  7. Postnatal and adult neurogenesis in the development of human disease.

    PubMed

    Danzer, Steve C

    2008-10-01

    The mammalian brain contains a population of neurons that are continuously generated from late embryogenesis through adulthood-after the generation of almost all other neuronal types. This brain region-the hippocampal dentate gyrus-is in a sense, therefore, persistently immature. Postnatal and adult neurogenesis is likely an essential feature of the dentate, which is critical for learning and memory. Protracted neurogenesis after birth would allow the new cells to develop in conjunction with external events-but it may come with a price: while neurogenesis in utero occurs in a protected environment, children and adults are exposed to any number of hazards, such as toxins and infectious agents. Mature neurons might be resistant to such exposures, but new neurons may be vulnerable. Consistent with this prediction, in adult rodents seizures disrupt the integration of newly generated granule cells, whereas mature granule cells are comparatively unaffected. Significantly, abnormally interconnected cells may contribute to epileptogenesis and/or associated cognitive and memory deficits. Finally, studies increasingly indicate that new granule cells are extremely sensitive to a host of endogenous and exogenous factors, raising the possibility that disrupted granule cell integration may be a common feature of many neurological diseases.

  8. 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.

  9. 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.

  10. Alternative Sources of Adult Stem Cells: Human Amniotic Membrane

    NASA Astrophysics Data System (ADS)

    Wolbank, Susanne; van Griensven, Martijn; Grillari-Voglauer, Regina; Peterbauer-Scherb, Anja

    Human amniotic membrane is a highly promising cell source for tissue engineering. The cells thereof, human amniotic epithelial cells (hAEC) and human amniotic mesenchymal stromal cells (hAMSC), may be immunoprivileged, they represent an early developmental status, and their application is ethically uncontroversial. Cell banking strategies may use freshly isolated cells or involve in vitro expansion to increase cell numbers. Therefore, we have thoroughly characterized the effect of in vitro cultivation on both phenotype and differentiation potential of hAEC. Moreover, we present different strategies to improve expansion including replacement of animal-derived supplements by human platelet products or the introduction of the catalytic subunit of human telomerase to extend the in vitro lifespan of amniotic cells. Characterization of the resulting cultures includes phenotype, growth characteristics, and differentiation potential, as well as immunogenic and immunomodulatory properties.

  11. 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

  12. 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.

  13. Nasopharyngeal carriage of Streptococcus pneumoniae in adults infected with human immunodeficiency virus in Jakarta, Indonesia.

    PubMed

    Harimurti, Kuntjoro; Saldi, Siti R F; Dewiasty, Esthika; Khoeri, Miftahuddin M; Yunihastuti, Evi; Putri, Tiara; Tafroji, Wisnu; Safari, Dodi

    2016-01-01

    This study investigated the distribution of serotype and antimicrobial susceptibility of Streptococcus pneumoniae carried by adults infected with human immunodeficiency virus (HIV) in Jakarta, Indonesia. Specimens of nasopharyngeal swab were collected from 200 HIV infected adults aged 21 to 63 years. Identification of S. pneumoniae was done by optochin susceptibility test and PCR for the presence of psaA and lytA genes. Serotyping was performed with sequential multiplex PCR and antibiotic susceptibility with the disk diffusion method. S. pneumoniae strains were carried by 10% adults with serotype 6A/B 20% was common serotype among cultured strains in 20 adults. Most of isolates were susceptible to chloramphenicol (80%) followed by clindamycin (75%), erythromycin (75%), penicillin (55%), and tetracycline (50%). This study found resistance to sulphamethoxazole/trimethoprim was most common with only 15% of strains being susceptible. High non-susceptibility to sulphamethoxazole/trimethoprim was observed in S. pneumoniae strains carried by HIV infected adults in Jakarta, Indonesia.

  14. 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.

  15. 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.

  16. Molecular Mechanism of Adult Neurogenesis and its Association with Human Brain Diseases

    PubMed Central

    Liu, He; Song, Ni

    2016-01-01

    Recent advances in neuroscience challenge the old dogma that neurogenesis occurs only during embryonic development. Mounting evidence suggests that functional neurogenesis occurs throughout adulthood. This review article discusses molecular factors that affect adult neurogenesis, including morphogens, growth factors, neurotransmitters, transcription factors, and epigenetic factors. Furthermore, we summarize and compare current evidence of associations between adult neurogenesis and human brain diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and brain tumors. PMID:27375363

  17. [Dietary phytoestrogen and its potential benefits in adult human health].

    PubMed

    Garrido, Argelia; de la Maza, María Pía; Valladares, Luis

    2003-11-01

    Human diet contains a series of bioactive vegetal compounds that can improve human health. Among these, there has been a special interest for phytoestrogens. This article reviews the evidence about the potential benefits of phytoestrogens for human health. Forty eight manuscripts were selected for their study design and relevance to human health. The cell growth inhibitory effects of phytoestrogens and their implication in breast cancer are reviewed. Also the effects of these compounds on serum lipid levels and the effectiveness of a phytoestrogen derivate, ipriflavone, on the prevention of osteoporosis are analyzed. Although these compounds have a great potential for improving health, there is still not enough evidence to recommend the routine use of phytoestrogens.

  18. 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.

  19. 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.

  20. 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

  1. A century of trends in adult human height.

    PubMed

    2016-07-26

    Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5-22.7) and 16.5 cm (13.3-19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8-144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.

  2. A century of trends in adult human height

    PubMed Central

    2016-01-01

    Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries. DOI: http://dx.doi.org/10.7554/eLife.13410.001 PMID:27458798

  3. Immune physiology and oogenesis in fetal and adult humans, ovarian infertility, and totipotency of adult ovarian stem cells.

    PubMed

    Bukovsky, Antonin; Caudle, Michael R; Virant-Klun, Irma; Gupta, Satish K; Dominguez, Roberto; Svetlikova, Marta; Xu, Fei

    2009-03-01

    It is still widely believed that while oocytes in invertebrates and lower vertebrates are periodically renewed throughout life, oocytes in humans and higher vertebrates are formed only during the fetal/perinatal period. However, this dogma is questioned, and clashes with Darwinian evolutionary theory. Studies of oogenesis and follicular renewal from ovarian stem cells (OSCs) in adult human ovaries, and of the role of third-party bone marrow-derived cells (monocyte-derived tissue macrophages and T lymphocytes) could help provide a better understanding of the causes of ovarian infertility, its prevention, and potential treatment. We have reported differentiation of distinct cell types from OSC and the production of new eggs in cultures derived from premenopausal and postmenopausal human ovaries. OSCs are also capable of producing neural/neuronal cells in vitro after sequential stimulation with sex steroid combinations. Hence, OSC represent a unique type of totipotent adult stem cells, which could be utilized for autologous treatment of premature ovarian failure and also for autologous stem cell therapy of neurodegenerative diseases without use of allogeneic embryonic stem cells or somatic cell nuclear transfer. The in vivo application of sex steroid combinations may augment the proliferation of existing neural stem cells and their differentiation into mature neuronal cells (systemic regenerative therapy). Such treatment may also stimulate the transdifferentiation of autologous neural stem cell precursors into neural stem cells useful for topical or systemic regenerative treatment.

  4. Hesperetin induces melanin production in adult human epidermal melanocytes.

    PubMed

    Usach, Iris; Taléns-Visconti, Raquel; Magraner-Pardo, Lorena; Peris, José-Esteban

    2015-06-01

    One of the major sources of flavonoids for humans are citrus fruits, hesperidin being the predominant flavonoid. Hesperetin (HSP), the aglycon of hesperidin, has been reported to provide health benefits such as antioxidant, anti-inflammatory and anticarcinogenic effects. However, the effect of HSP on skin pigmentation is not clear. Some authors have found that HSP induces melanogenesis in murine B16-F10 melanoma cells, which, if extrapolated to in vivo conditions, might protect skin against photodamage. Since the effect of HSP on normal melanocytes could be different to that observed on melanoma cells, the described effect of HSP on murine melanoma cells has been compared to the effect obtained using normal human melanocytes. HSP concentrations of 25 and 50 µM induced melanin synthesis and tyrosinase activity in human melanocytes in a concentration-dependent manner. Compared to control melanocytes, 25 µM HSP increased melanin production and tyrosinase activity 1.4-fold (p < 0.01) and 1.1-fold (p < 0.01), respectively, and the corresponding increases in the case of 50 µM HSP were 1.9-fold (p < 0.001) and 1.3-fold (p < 0.001). Therefore, HSP could be considered a valuable photoprotective substance if its capacity to increase melanin production in human melanocyte cultures could be reproduced on human skin.

  5. Comparison of proliferating cells between human adult and fetal eccrine sweat glands.

    PubMed

    Li, Hai-Hong; Fu, Xiao-Bing; Zhang, Lei; Zhou, Gang

    2008-04-01

    Studies of sweat glands had demonstrated that there were degenerating cells and proliferating cells in the eccrine sweat glands. To compare the differences in the proliferating cells between human adult and fetal eccrine sweat glands, immunostaining of proliferating-associated proliferating cell nuclear antigen (PCNA) and Ki67 nuclear antigen (Ki67) was performed, and the location and the percentage of the positive staining cells were analyzed. The results showed that a few cells of the secretory and ductal portion in both the adult and fetal eccrine sweat glands stained positive with Ki67 and PCNA. The labeling index of PCNA in adult eccrine sweat glands was 34.71 +/- 8.37%, while that in the fetal was 62.72 +/- 6.54%. The labeling index of PCNA in fetal eccrine sweat glands was higher than that in adult. Myoepithelial cells were negative staining with anti-PCNA antibody in adult eccrine sweat glands, while in the fetal a few myoepithelial cells were positive staining. Labeling index of Ki67 in adult eccrine sweat glands was similar to that in the fetal, ranging from 0.5 to 4.3%. Myoepithelial cells of the adult and fetal eccrine sweat glands both were negative staining with anti-Ki67 antibody. We concluded that the myoepithelial cells had proliferating ability only in fetal eccrine sweat glands, and that the proliferating ability of fetal eccrine sweat glands was stronger than that of the adult.

  6. 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

  7. 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

  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. Androgen responsive adult human prostatic epithelial cell lines immortalized by human papillomavirus 18.

    PubMed

    Bello, D; Webber, M M; Kleinman, H K; Wartinger, D D; Rhim, J S

    1997-06-01

    Prostate cancer and benign tumors of the prostate are the two most common neoplastic diseases in men in the United States, however, research on their causes and treatment has been slow because of the difficulty in obtaining fresh samples of human tissue and a lack of well characterized cell lines which exhibit growth and differentiation characteristics of normal prostatic epithelium. Non-neoplastic adult human prostatic epithelial cells from a white male donor were immortalized with human papillomavirus 18 which resulted in the establishment of the RWPE-1 cell line. Cells from the RWPE-1 cell line were further transformed by v-Ki-ras to establish the RWPE-2 cell line. The objectives of this study were to: (1) establish the prostatic epithelial origin and androgen responsiveness of RWPE-1 and RWPE-2 cell lines; (2) examine their response to growth factors; and (3) establish the malignant characteristics of the RWPE-2 cell line. Immunoperoxidase staining showed that both RWPE-1 and RWPE-2 cells express cytokeratins 8 and 18, which are characteristic of luminal prostatic epithelial cells, but they also coexpress basal cell cytokeratins. These cell lines show growth stimulation and prostate specific antigen (PSA) and androgen receptor (AR) expression in response to the synthetic androgen mibolerone, which establishes their prostatic epithelial origin. Both cell lines also show a dose-dependent growth stimulation by EGF and bFGF and growth inhibition when exposed to TGF-beta, however, the transformed RWPE-2 cells are less responsive. RWPE-1 cells neither grow in agar nor form tumors when injected into nude mice with or without Matrigel. However, RWPE-2 cells form colonies in agar and tumors in nude mice. In the in vitro invasion assay, RWPE-1 cells are not invasive whereas RWPE-2 cells are invasive. Nuclear expression of p53 and Rb proteins was heterogeneous but detectable by immunostaining in both cell lines. The RWPE-1 cells, which show many normal cell

  10. 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

  11. Global and local processing in adult humans (Homo sapiens), 5-year-old children (Homo sapiens), and adult cotton-top tamarins (Saguinus oedipus).

    PubMed

    Neiworth, Julie J; Gleichman, Amy J; Olinick, Anne S; Lamp, Kristen E

    2006-11-01

    This study compared adults (Homo sapiens), young children (Homo sapiens), and adult tamarins (Saguinus oedipus) while they discriminated global and local properties of stimuli. Subjects were trained to discriminate a circle made of circle elements from a square made of square elements and were tested with circles made of squares and squares made of circles. Adult humans showed a global bias in testing that was unaffected by the density of the elements in the stimuli. Children showed a global bias with dense displays but discriminated by both local and global properties with sparse displays. Adult tamarins' biases matched those of the children. The striking similarity between the perceptual processing of adult monkeys and humans diagnosed with autism and the difference between this and normatively developing human perception is discussed.

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. Fus1 KO Mouse As a Model of Oxidative Stress-Mediated Sporadic Alzheimer's Disease: Circadian Disruption and Long-Term Spatial and Olfactory Memory Impairments

    PubMed Central

    Coronas-Samano, Guillermo; Baker, Keeley L.; Tan, Winston J. T.; Ivanova, Alla V.; Verhagen, Justus V.

    2016-01-01

    Insufficient advances in the development of effective therapeutic treatments of sporadic Alzheimer's Disease (sAD) to date are largely due to the lack of sAD-relevant animal models. While the vast majority of models do recapitulate AD's hallmarks of plaques and tangles by virtue of tau and/or beta amyloid overexpression, these models do not reflect the fact that in sAD (unlike familial AD) these genes are not risk factors per se and that other mechanisms like oxidative stress, metabolic dysregulation and inflammation play key roles in AD etiology. Here we characterize and propose the Fus1 KO mice that lack a mitochondrial protein Fus1/Tusc2 as a new sAD model. To establish sAD relevance, we assessed sAD related deficits in Fus1 KO and WT adult mice of 4–5 months old, the equivalent human age when the earliest cognitive and olfactory sAD symptoms arise. Fus1 KO mice showed oxidative stress (increased levels of ROS, decreased levels of PRDX1), disruption of metabolic homeostasis (decreased levels of ACC2, increased phosphorylation of AMPK), autophagy (decreased levels of LC3-II), PKC (decreased levels of RACK1) and calcium signaling (decreased levels of Calb2) in the olfactory bulb and/or hippocampus. Mice were behaviorally tested using objective and accurate video tracking (Noldus), in which Fus1 KO mice showed clear deficits in olfactory memory (decreased habituation/cross-habituation in the short and long term), olfactory guided navigation memory (inability to reduce their latency to find the hidden cookie), spatial memory (learning impairments on finding the platform in the Morris water maze) and showed more sleep time during the diurnal cycle. Fus1 KO mice did not show clear deficits in olfactory perception (cross-habituation), association memory (passive avoidance) or in species-typical behavior (nest building) and no increased anxiety (open field, light-dark box) or depression/anhedonia (sucrose preference) at this relatively young age. These neurobehavioral

  18. 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.

  19. 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.

  20. 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

  1. Impact of growth hormone hypersecretion on the adult human kidney.

    PubMed

    Grunenwald, Solange; Tack, Ivan; Chauveau, Dominique; Bennet, Antoine; Caron, Philippe

    2011-12-01

    Acromegaly is most often secondary to a GH-secreting pituitary adenoma with increased Insulin-like Growth Factor type 1 (IGF-1) level. The consequences of GH/IGF-1 hypersecretion reflect the diversity of action of these hormones. The genes of the GH receptor (GHR), IGF-1, IGF-1 receptor (IGF-1R) and IGF-binding proteins (IGF-BP) are physiologically expressed in the adult kidney, suggesting a potential role of the somatotropic axis on renal structure and functions. The expression of these proteins is highly organized and differs according to the anatomical and functional segments of the nephron suggesting different roles of GH and IGF-1 in these segments. In animals, chronic exposure to high doses of GH induces glomerulosclerosis and increases albuminuria. Studies in patients with GH hypersecretion have identified numerous targets of GH/IGF-1 axis on the kidney: 1) an impact on renal filtration with increased glomerular filtration rate (GFR), 2) a structural impact with an increase in kidney weight and glomerular hypertrophy, and 3) a tubular impact leading to hyperphosphatemia, hypercalciuria and antinatriuretic effects. Despite the increased glomerular filtration rate observed in patients with GH hypersecretion, GH is an inefficient treatment for chronic renal failure. GH and IGF-1 seem to be involved in the physiopathology of diabetic nephropathy; this finding offers the possibility of targeting the GH/IGF-1 axis for the prevention and the treatment of diabetic nephropathy.

  2. Testosterone affects language areas of the adult human brain

    PubMed Central

    Hahn, Andreas; Kranz, Georg S.; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F.

    2016-01-01

    Abstract Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high‐dose hormone application in adult female‐to‐male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel‐based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting‐state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone‐dependent neuroplastic adaptations in adulthood within language‐specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738–1748, 2016. © 2016 Wiley Periodicals, Inc. PMID:26876303

  3. Bacteriology of severe periodontitis in young adult humans.

    PubMed Central

    Moore, W E; Holdeman, L V; Smibert, R M; Hash, D E; Burmeister, J A; Ranney, R R

    1982-01-01

    A total of 78 bacteriological samples were taken from the supragingival tooth surface after superficial cleaning with toothpicks or from the periodontal sulci of 42 affected sites in 21 adolescents or young adults with severe generalized periodontitis. Of 190 bacterial species, subspecies, or serotypes detected among 2,723 isolates, 11 species exceeded 1% of the subgingival flora and were most closely associated with the diseased sulci. Eleven others were also sufficiently frequent to be suspect agents of tissue destruction. Many of these species are known pathogens of other body sites. In addition, 10 species of Treponema were isolated. One of these and the "large treponeme" were also more closely associated with severe periodontitis than they were with healthy sites or gingivitis. There were highly significant differences between the composition of the flora of the affected sulci and the flora of (i) the adjacent supragingival tooth surface, (ii) the gingival crevice of periodontally healthy people, and (iii) sites with a gingival index score of 0 or 2 in experimental gingivitis studies. The floras of different individuals were also significantly different. There was no statistically detectable effect of sampling per se upon the composition of the flora of subsequent samples from the same sites. The composition of the supragingival flora of the patients with severe generalized periodontitis that had serum antibody to Actinobacillus actinomycetemcomitans was significantly different from the supragingival flora of patients without this serum antibody. However, there was no statistically significant difference in the composition of their subgingival floras. PMID:7152665

  4. Testosterone affects language areas of the adult human brain.

    PubMed

    Hahn, Andreas; Kranz, Georg S; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F; Lanzenberger, Rupert

    2016-05-01

    Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high-dose hormone application in adult female-to-male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel-based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting-state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone-dependent neuroplastic adaptations in adulthood within language-specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738-1748, 2016. © 2016 Wiley Periodicals, Inc.

  5. 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.

  6. Disruption of Aedes aegypti Olfactory System Development through Chitosan/siRNA Nanoparticle Targeting of semaphorin-1a

    PubMed Central

    Mysore, Keshava; Flannery, Ellen M.; Tomchaney, Michael; Severson, David W.; Duman-Scheel, Molly

    2013-01-01

    Despite the devastating impact of mosquito-borne illnesses on human health, surprisingly little is known about mosquito developmental biology, including development of the olfactory system, a tissue of vector importance. Analysis of mosquito olfactory developmental genetics has been hindered by a lack of means to target specific genes during the development of this sensory system. In this investigation, chitosan/siRNA nanoparticles were used to target semaphorin-1a (sema1a) during olfactory system development in the dengue and yellow fever vector mosquito Aedes aegypti. Immunohistochemical analyses and anterograde tracing of antennal sensory neurons, which were used to track the progression of olfactory development in this species, revealed antennal lobe defects in sema1a knockdown fourth instar larvae. These findings, which correlated with a larval odorant tracking behavioral phenotype, identified previously unreported roles for Sema1a in the developing insect larval olfactory system. Analysis of sema1a knockdown pupae also revealed a number of olfactory phenotypes, including olfactory receptor neuron targeting and projection neuron defects coincident with a collapse in the structure and shape of the antennal lobe and individual glomeruli. This study, which is to our knowledge the first functional genetic analysis of insect olfactory development outside of D. melanogaster, identified critical roles for Sema1a during Ae. aegypti larval and pupal olfactory development and advocates the use of chitosan/siRNA nanoparticles as an effective means of targeting genes during post-embryonic Ae. aegypti development. Use of siRNA nanoparticle methodology to understand sensory developmental genetics in mosquitoes will provide insight into the evolutionary conservation and divergence of key developmental genes which could be exploited in the development of both common and species-specific means for intervention. PMID:23696908

  7. 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

  8. 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.

  9. Chronic Spinal Injury Repair by Olfactory Bulb Ensheathing Glia and Feasibility for Autologous Therapy

    PubMed Central

    Muñoz-Quiles, Cintia; Santos-Benito, Fernando F.; Llamusí, M. Beatriz; Ramón-Cueto, Almudena

    2009-01-01

    Olfactory bulb ensheathing glia (OB-OEG) promote repair of spinal cord injury (SCI) in rats after transplantation at acute or subacute (up to 45 days) stages. The most relevant clinical scenario in humans, however, is chronic SCI, in which no more major cellular or molecular changes occur at the injury site; this occurs after the third month in rodents. Whether adult OB-OEG grafts promote repair of severe chronic SCI has not been previously addressed. Rats with complete SCI that were transplanted with OB-OEG 4 months after injury exhibited progressive improvement in motor function and axonal regeneration from different brainstem nuclei across and beyond the SCI site. A positive correlation between motor outcome and axonal regeneration suggested a role for brainstem neurons in the recovery. Functional and histological outcomes did not differ at subacute or chronic stages. Thus, autologous transplantation is a feasible approach as there is time for patient stabilization and OEG preparation in human chronic SCI; the healing effects of OB-OEG on established injuries may offer new therapeutic opportunities for chronic SCI patients. PMID:19915486

  10. 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.

  11. Taxis assays measure directional movement of mosquitoes to olfactory cues

    PubMed Central

    2013-01-01

    Background Malaria control methods targeting indoor-biting mosquitoes have limited impact on vectors that feed and rest outdoors. Exploiting mosquito olfactory behaviour to reduce blood-feeding outdoors might be a sustainable approach to complement existing control strategies. Methodologies that can objectively quantify responses to odour under realistic field conditions and allow high-throughput screening of many compounds are required for development of effective odour-based control strategies. Methods The olfactory responses of laboratory-reared Anopheles gambiae in a semi-field tunnel and A. arabiensis females in an outdoor field setting to three stimuli, namely whole human odour, a synthetic blend of carboxylic acids plus carbon dioxide and CO2 alone at four distances up to 100 metres were measured in two experiments using three-chambered taxis boxes that allow mosquito responses to natural or experimentally-introduced odour cues to be quantified. Results Taxis box assays could detect both activation of flight and directional mosquito movement. Significantly more (6-18%) A. arabiensis mosquitoes were attracted to natural human odour in the field up to 30 metres compared to controls, and blended synthetic human odours attracted 20% more A. gambiae in the semi-field tunnel up to 70 metres. Whereas CO2 elicited no response in A. arabiensis in the open field, it was attractive to A. gambiae up to 50 metres (65% attraction compared to 36% in controls). Conclusions We have developed a simple reproducible system to allow for the comparison of compounds that are active over medium- to long-ranges in semi-field or full-field environments. Knowing the natural range of attraction of anopheline mosquitoes to potential blood sources has substantial implications for the design of malaria control strategies, and adds to the understanding of olfactory behaviour in mosquitoes. This experimental strategy could also be extended from malaria vectors to other motile arthropods of

  12. 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

  13. Hunger state affects both olfactory abilities and gustatory sensitivity.

    PubMed

    Hanci, Deniz; Altun, Huseyin

    2016-07-01

    Chemical senses such as odor, taste and appearance are directly related with appetite. Understanding the relation between appetite and flavor is getting more important due to increasing number of obese patients worldwide. The literature on the studies investigating the change in olfactory abilities and gustatory sensitivity mostly performed using food-related odors and tastes rather than standardized tests were developed to study olfaction and gustation. Therefore, results are inconsistent and the relationship between olfactory and gustatory sensitivity with respect to the actual state of human satiety is still not completely understood. Here, for the first time in literature, we investigated the change in both olfactory abilities and gustatory sensitivity in hunger and in satiety using 123 subjects (37 men, 86 women; mean age 31.4 years, age range 21-41 years). The standardized Sniffin' Sticks Extended Test and Taste Strips were used for olfactory testing and gustatory sensitivity, respectively. TDI score (range 1-48) was calculated as the collective scores of odor threshold (T), odor discrimination (D) and odor identification (I). The evaluation was performed in two successive days where the hunger state of test subjects was confirmed by blood glucose test strips (mean blood glucose level 90.0 ± 5.6 mg/dl in hunger and 131.4 ± 8.1 mg/dl in satiety). The results indicated statistically significant decrease in olfaction in satiety compared to hunger (mean TDI 39.3 ± 1.1 in hunger, 37.4 ± 1.1 in satiety, p < 0.001). The comparison of gustatory sensitivity indicated significantly higher sensitivity to sweet, sour and salty in hunger (p < 0.001), but significantly higher sensitivity to bitter tastant in satiety (p < 0.001). With this prospective study, we were able to show that both olfactory abilities and gustatory sensitivity were affected by hunger state.

  14. 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…

  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. 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.

  17. Genetic and functional characterization of clonally derived adult human brown adipocytes

    PubMed Central

    Shinoda, Kosaku; Luijten, Ineke H N; Hasegawa, Yutaka; Hong, Haemin; Sonne, Si B; Kim, Miae; Xue, Ruidan; Chondronikola, Maria; Cypess, Aaron M; Tseng, Yu-Hua; Nedergaard, Jan; Sidossis, Labros S; Kajimura, Shingo

    2015-01-01

    Brown adipose tissue (BAT) acts in mammals as a natural defense system against hypothermia, and its activation to a state of increased energy expenditure is believed to protect against the development of obesity. Even though the existence of BAT in adult humans has been widely appreciated1–8, its cellular origin and molecular identity remain elusive largely because of high cellular heterogeneity within various adipose tissue depots. To understand the nature of adult human brown adipocytes at single cell resolution, we isolated clonally derived adipocytes from stromal vascular fractions of adult human BAT from two individuals and globally analyzed their molecular signatures. We used RNA sequencing followed by unbiased genome-wide expression analyses and found that a population of uncoupling protein 1 (UCP1)-positive human adipocytes possessed molecular signatures resembling those of a recruitable form of thermogenic adipocytes (that is, beige adipocytes). In addition, we identified molecular markers that were highly enriched in UCP1-positive human adipocytes, a set that included potassium channel K3 (KCNK3) and mitochondrial tumor suppressor 1 (MTUS1). Further, we functionally characterized these two markers using a loss-of-function approach and found that KCNK3 and MTUS1 were required for beige adipocyte differentiation and thermogenic function. The results of this study present new opportunities for human BAT research, such as facilitating cell-based disease modeling and unbiased screens for thermogenic regulators. PMID:25774848

  18. Characterization of colony-forming cells in adult human articular cartilage.

    PubMed

    Ozbey, Ozlem; Sahin, Zeliha; Acar, Nuray; Ozcelik, Filiz Tepekoy; Ozenci, Alpay Merter; Koksoy, Sadi; Ustunel, Ismail

    2014-06-01

    Recent studies have shown that adult human articular cartilage contains stem-like cells within the native structure. In this study, we aimed to determine the localization of putative stem cell markers such as CD90, STRO-1, OCT-3/4, CD105 and CD166 in adult human articular cartilage tissue sections and demonstrate the expression of these markers within the expanded surface zone colony-forming (CF) cells and evaluate their differentiation potential. Biopsy samples were either fixed immediately for immunohistochemical analyses or processed for in vitro cell culture. Immunohistochemical and flow cytometry analyses were performed by using CD90, STRO-1, OCT-3/4, CD105 and CD166 antibodies. Isolated colony-forming (CF) cells were further stimulated, by using the appropriate growth factors in their pellet culture, to obtain cartilage, bone and adipose lineages. We observed that the expression of the stem cell markers were in various zones of the human adult cartilage. Flow cytometry results showed that in CF cells the expression of CD90 and CD166 was high, while OCT-3/4 was low. We also determined that CF cells could be stimulated towards cartilage, bone and adipose lineages. The results of this research support the idea that the resident stem-like cells in adult human articular cartilage express these putative stem cell markers, but further experimental investigations are needed to determine the precise localization of these cells.

  19. Perspectives on Adult Education, Human Resource Development, and the Emergence of Workforce Development

    ERIC Educational Resources Information Center

    Jacobs, Ronald L.

    2006-01-01

    This article presents a perspective on the relationship between adult education and human resource development of the past two decades and the subsequent emergence of workforce development. The lesson taken from the article should be more than simply a recounting of events related to these fields of study. Instead, the more general lesson may be…

  20. Treatment of Human-Caused Trauma: Attrition in the Adult Outcomes Research

    ERIC Educational Resources Information Center

    Matthieu, Monica; Ivanoff, Andre

    2006-01-01

    Attrition or dropout is the failure of a participant to complete, comply, or the prematurely discontinuation or discharge from treatment, resulting in lost data and affecting outcomes. This review of 10 years of adult posttraumatic stress disorder (PTSD) treatment outcome literature specific to Criterion A events of human origin examines how…

  1. Bridging the Gap between Human Resource Development and Adult Education: Part One, Assumptions, Definitions, and Critiques

    ERIC Educational Resources Information Center

    Hatcher, Tim; Bowles, Tuere

    2006-01-01

    Human resource development (HRD) as a scholarly endeavor and as a practice is often criticized in the adult education (AE) literature and by AE scholars as manipulative and oppressive and, through training and other interventions, controlling workers for strictly economic ends (Baptiste, 2001; Cunningham, 2004; Schied, 2001; Welton, 1995).…

  2. Emotions and Human Concern: Adult Education and the Philosophical Thought of Martha Nussbaum

    ERIC Educational Resources Information Center

    Plumb, Donovan

    2014-01-01

    This article argues that philosopher Martha Nussbaum's reflections on the role of the emotions in human flourishing can contribute in important ways to our understanding of the emotions in adult education contexts. The article summarises Nussbaum's exploration of the contributions of classical philosophers like Socrates, Aristotle, and…

  3. Bridging the Gap between Human Resource Development and Adult Education: Part Two, the Critical Turn

    ERIC Educational Resources Information Center

    Hatcher, Tim; Bowles, Tuere

    2006-01-01

    Human resource development (HRD) as a scholarly endeavor and as a practice is often criticized in the adult education (AE) literature and by AE scholars as manipulative and oppressive and, through training and other interventions, controlling workers for strictly economic ends (Baptiste, 2001; Cunningham, 2004; Schied, 2001; Welton, 1995). The…

  4. NIRS Measurement of Venous Oxygen Saturation in the Adult Human Head

    NASA Astrophysics Data System (ADS)

    Brown, Derek W.; Haensse, Daniel; Bauschatz, Andrea; Wolf, Martin

    Provided that both the breathing frequency remains constant and that the temporal resolution of the instrument is sufficiently high, NIRS spiroximetry enables measurement of cerebral SvO2 in healthy human adults. Furthermore, simultaneous measurements of StO2, SaO2, and SvO2 enable calculation of both OEF and the compartmental distribution of cerebral blood volume.

  5. Complete Genome Sequence of Human Adenovirus 7 Associated with Fatal Adult Pneumonia.

    PubMed

    Yatsyshina, Svetlana B; Ageeva, Margarita R; Deviatkin, Andrey A; Pimkina, Ekaterina V; Markelov, Mikhail L; Dedkov, Vladimir G; Safonova, Marina V; Shumilina, Elena Y; Lukashev, Alexander N; Shipulin, German A

    2016-10-27

    Human adenovirus 7 (hAdv7) 19BOVLB/Volgograd/Rus/2014 was isolated from the autopsy material from an adult with fatal pneumonia in Volgograd, Russia, in March 2014. Whole-genome sequencing of the virus isolate was performed.

  6. Perspectives on Adult Education, Human Resource Development, and the Emergence of Workforce Development

    ERIC Educational Resources Information Center

    Jacobs, Ronald L.

    2014-01-01

    This article presents a perspective on the relationship between adult education and human resource development of the past two decades and the subsequent emergence of workforce development. The lesson taken from the article should be more than simply a recounting of events related to these fields of study. Instead, the more general lesson may be…

  7. Bridging the Gap between Human Resource Development and Adult Education: Part Two, the Critical Turn

    ERIC Educational Resources Information Center

    Hatcher, Tim; Bowles, Tuere

    2014-01-01

    Human resource development (HRD) as a scholarly endeavor and as a practice is often criticized in the adult education (AE) literature and by AE scholars as manipulative and oppressive and, through training and other interventions, controlling workers for strictly economic ends (Baptiste, 2001; Cunningham, 2004; Schied, 2001; Welton, 1995). The…

  8. Bridging the Gap between Human Resource Development and Adult Education: Part One, Assumptions, Definitions, and Critiques

    ERIC Educational Resources Information Center

    Hatcher, Tim; Bowles, Tuere

    2013-01-01

    Human resource development (HRD) as a scholarly endeavor and as a practice is often criticized in the adult education (AE) literature and by AE scholars as manipulative and oppressive and, through training and other interventions, controlling workers for strictly economic ends (Baptiste, 2001; Cunningham, 2004; Schied, 2001; Welton, 1995).…

  9. Concept Maps: Practice Applications in Adult Education and Human Resource Development

    ERIC Educational Resources Information Center

    Daley, Barbara J.

    2010-01-01

    Concept maps can be used as both a cognitive and constructivist learning strategy in teaching and learning in adult education and human resource development. The maps can be used to understand course readings, analyze case studies, develop reflective thinking and enhance research skills. The creation of concept maps can also be supported by the…

  10. Equality and Human Capital: Conflicting Concepts within State-Funded Adult Education in Ireland

    ERIC Educational Resources Information Center

    Hurley, Kevin

    2015-01-01

    This article offers a critique of the concept of equality as it informs the White Paper on Adult Education: Learning for Life (2000). It also outlines the extent to which human capital theory can be seen to have effectively colonised lifelong learning from the outset of its adoption by the European Union with highly constraining implications for…

  11. Canonical Genetic Signatures of the Adult Human Brain

    PubMed Central

    Hawrylycz, Michael; Miller, Jeremy A.; Menon, Vilas; Feng, David; Dolbeare, Tim; Guillozet-Bongaarts, Angela L.; Jegga, Anil G.; Aronow, Bruce J.; Lee, Chang-Kyu; Bernard, Amy; Glasser, Matthew F.; Dierker, Donna L.; Menche, Jörge; Szafer, Aaron; Collman, Forrest; Grange, Pascal; Berman, Kenneth A.; Mihalas, Stefan; Yao, Zizhen; Stewart, Lance; Barabási, Albert-László; Schulkin, Jay; Phillips, John; Ng, Lydia; Dang, Chinh; Haynor, David R.; Jones, Allan; Van Essen, David C.; Koch, Christof; Lein, Ed

    2015-01-01

    The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure, and function. We applied a correlation-based metric of “differential stability” (DS) to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing meso-scale genetic organization. The highest DS genes are highly biologically relevant, with enrichment for brain-related biological annotations, disease associations, drug targets, and literature citations. Using high DS genes we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components, and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely-patterned genes displayed dramatic shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry. PMID:26571460

  12. 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

  13. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted...

  14. 40 CFR 26.1704 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted before April 7, 2006. 26.1704 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted...

  15. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated...

  16. 40 CFR 26.1704 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted before April 7, 2006. 26.1704 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted...

  17. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted...

  18. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted...

  19. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated...

  20. 40 CFR 26.1704 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted before April 7, 2006. 26.1704 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted...

  1. Self-Control and Impulsiveness in Nondieting Adult Human Females: Effects of Visual Food Cues and Food Deprivation

    ERIC Educational Resources Information Center

    Forzano, Lori-Ann B.; Chelonis, John J.; Casey, Caitlin; Forward, Marion; Stachowiak, Jacqueline A.; Wood, Jennifer

    2010-01-01

    Self-control can be defined as the choice of a larger, more delayed reinforcer over a smaller, less delayed reinforcer, and impulsiveness as the opposite. Previous research suggests that exposure to visual food cues affects adult humans' self-control. Previous research also suggests that food deprivation decreases adult humans' self-control. The…

  2. Rehabilitation in adults with human immunodeficiency virus-related diseases.

    PubMed

    O'Dell, M W; Dillon, M E

    1992-06-01

    The acquired immunodeficiency syndrome is a fatal disorder of cell-mediated immunity caused by the human immunodeficiency virus (HIV). As many as one million Americans infected with HIV can expect improved survival with more advanced treatment approaches. Complications of HIV infection occur in the brain, spinal cord, muscle, nerve, joints and other organ systems, which lead to extensive impairments. As survival increases, rehabilitation professionals can anticipate a greater number of referrals for the assessment and management of physical disability in persons with HIV infection. This article reviews HIV-related disease, impairment, disability and handicap pertinent to rehabilitation medicine. An agenda for future research is also proposed. Current knowledge and models or rehabilitation care can be applied to HIV-related physical disability in an effort to improve overall quality of life.

  3. Computational Approaches for Decoding Select Odorant-Olfactory Receptor Interactions Using Mini-Virtual Screening

    PubMed Central

    Harini, K.; Sowdhamini, Ramanathan

    2015-01-01

    Olfactory receptors (ORs) belong to the class A G-Protein Coupled Receptor superfamily of proteins. Unlike G-Protein Coupled Receptors, ORs exhibit a combinatorial response to odors/ligands. ORs display an affinity towards a range of odor molecules rather than binding to a specific set of ligands and conversely a single odorant molecule may bind to a number of olfactory receptors with varying affinities. The diversity in odor recognition is linked to the highly variable transmembrane domains of these receptors. The purpose of this study is to decode the odor-olfactory receptor interactions using in silico docking studies. In this study, a ligand (odor molecules) dataset of 125 molecules was used to carry out in silico docking using the GLIDE docking tool (SCHRODINGER Inc Pvt LTD). Previous studies, with smaller datasets of ligands, have shown that orthologous olfactory receptors respond to similarly-tuned ligands, but are dramatically different in their efficacy and potency. Ligand docking results were applied on homologous pairs (with varying sequence identity) of ORs from human and mouse genomes and ligand binding residues and the ligand profile differed among such related olfactory receptor sequences. This study revealed that homologous sequences with high sequence identity need not bind to the same/ similar ligand with a given affinity. A ligand profile has been obtained for each of the 20 receptors in this analysis which will be useful for expression and mutation studies on these receptors. PMID:26221959

  4. 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.

  5. Characterization of human foetal intestinal alkaline phosphatase. Comparison with the isoenzymes from the adult intestine and human tumour cell lines.

    PubMed Central

    Behrens, C M; Enns, C A; Sussman, H H

    1983-01-01

    The molecular structure of human foetal intestinal alkaline phosphatase was defined by high-resolution two-dimensional polyacrylamide-gel electrophoresis and amino acid inhibition studies. Comparison was made with the adult form of intestinal alkaline phosphatase, as well as with alkaline phosphatases isolated from cultured foetal amnion cells (FL) and a human tumour cell line (KB). Two non-identical subunits were isolated from the foetal intestinal isoenzyme, one having same molecular weight and isoelectric point as placental alkaline phosphatase, and the other corresponding to a glycosylated subunit of the adult intestinal enzyme. The FL-cell and KB-cell alkaline phosphatases were also found to contain two subunits similar to those of the foetal intestinal isoenzyme. Characterization of neuraminidase digests of the non-placental subunit showed it to be indistinguishable from the subunits of the adult intestinal isoenzyme. This implies that no new phosphatase structural gene is involved in the transition from the expression of foetal to adult intestinal alkaline phosphatase, but that the molecular changes involve suppression of the placental subunit and loss of neuraminic acid from the non-placental subunit. Enzyme-inhibition studies demonstrated an intermediate response to the inhibitors tested for the foetal intestinal, FL-cell and KB-cell isoenzymes when compared with the placental, adult intestinal and liver forms. This result is consistent with the mixed-subunit structure observed for the former set of isoenzymes. In summary, this study has defined the molecular subunit structure of the foetal intestinal form of alkaline phosphatase and has demonstrated its expression in a human tumour cell line. Images Fig. 1. PMID:6882358

  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. Larval food quantity affects the capacity of adult mosquitoes to transmit human malaria

    PubMed Central

    Shapiro, Lillian L. M.; Murdock, Courtney C.; Jacobs, Gregory R.; Thomas, Rachel J.; Thomas, Matthew B.

    2016-01-01

    Adult traits of holometabolous insects are shaped by conditions experienced during larval development, which might impact interactions between adult insect hosts and parasites. However, the ecology of larval insects that vector disease remains poorly understood. Here, we used Anopheles stephensi mosquitoes and the human malaria parasite Plasmodium falciparum, to investigate whether larval conditions affect the capacity of adult mosquitoes to transmit malaria. We reared larvae in two groups; one group received a standard laboratory rearing diet, whereas the other received a reduced diet. Emerging adult females were then provided an infectious blood meal. We assessed mosquito longevity, parasite development rate and prevalence of infectious mosquitoes over time. Reduced larval food led to increased adult mortality and caused a delay in parasite development and a slowing in the rate at which parasites invaded the mosquito salivary glands, extending the time it took for mosquitoes to become infectious. Together, these effects increased transmission potential of mosquitoes in the high food regime by 260–330%. Such effects have not, to our knowledge, been shown previously for human malaria and highlight the importance of improving knowledge of larval ecology to better understand vector-borne disease transmission dynamics. PMID:27412284

  9. 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.

  10. A humanized version of Foxp2 does not affect ultrasonic vocalization in adult mice.

    PubMed

    Hammerschmidt, K; Schreiweis, C; Minge, C; Pääbo, S; Fischer, J; Enard, W

    2015-11-01

    The transcription factor FOXP2 has been linked to severe speech and language impairments in humans. An analysis of the evolution of the FOXP2 gene has identified two amino acid substitutions that became fixed after the split of the human and chimpanzee lineages. Studying the functional consequences of these two substitutions in the endogenous Foxp2 gene of mice showed alterations in dopamine levels, striatal synaptic plasticity, neuronal morphology and cortico-striatal-dependent learning. In addition, ultrasonic vocalizations (USVs) of pups had a significantly lower average pitch than control littermates. To which degree adult USVs would be affected in mice carrying the 'humanized' Foxp2 variant remained unclear. In this study, we analyzed USVs of 68 adult male mice uttered during repeated courtship encounters with different females. Mice carrying the Foxp2(hum/hum) allele did not differ significantly in the number of call elements, their element structure or in their element composition from control littermates. We conclude that neither the structure nor the usage of USVs in adult mice is affected by the two amino acid substitutions that occurred in FOXP2 during human evolution. The reported effect for pup vocalization thus appears to be transient. These results are in line with accumulating evidence that mouse USVs are hardly influenced by vocal learning. Hence, the function and evolution of genes that are necessary, but not sufficient for vocal learning in humans, must be either studied at a different phenotypic level in mice or in other organisms.

  11. The mechanical properties of human ribs in young adult.

    PubMed

    Pezowicz, Celina; Głowacki, Maciej

    2012-01-01

    A good understanding of thoracic biomechanics is important for complete examination and control of chest behaviour under conditions of physiological and pathological work, and under the impact of external forces leading to traumatic loading of the chest. The purpose of the study was to analyse the mechanical properties of human ribs obtained from individuals under the age of 25 with scoliosis deformation and to correlate them with geometric properties of ribs. Thirty three fragments of ribs (9th to 12th) were tested in three-point bending. Rib fragments were collected intraoperatively from female patients treated for scoliosis in the thoracic, thoracolumbar, and lumbar spine. The results were used to determine the maximum failure force, stiffness, and Young's modulus. A significant relationship was found between the age and elastic modulus of the ribs. The analysis was carried out for two age groups, i.e., between the ages of 10 and 15 and between the ages of 16 and 22, and statistically significant differences were obtained for Young's modulus (p = 0.0001) amounting to, respectively, 2.79 ± 1.34 GPa for the first group and 7.44 ± 2.85 GPa for the second group. The results show a significant impact of age on the mechanical properties of ribs.

  12. Neural-competent cells of adult human dermis belong to the Schwann lineage.

    PubMed

    Etxaniz, Usue; Pérez-San Vicente, Adrián; Gago-López, Nuria; García-Dominguez, Mario; Iribar, Haizea; Aduriz, Ariane; Pérez-López, Virginia; Burgoa, Izaskun; Irizar, Haritz; Muñoz-Culla, Maider; Vallejo-Illarramendi, Ainara; Leis, Olatz; Matheu, Ander; Martín, Angel G; Otaegui, David; López-Mato, María Paz; Gutiérrez-Rivera, Araika; MacLellan, Robb; Izeta, Ander

    2014-11-11

    Resident neural precursor cells (NPCs) have been reported for a number of adult tissues. Understanding their physiological function or, alternatively, their activation after tissue damage or in vitro manipulation remains an unsolved issue. Here, we investigated the source of human dermal NPCs in adult tissue. By following an unbiased, comprehensive approach employing cell-surface marker screening, cell separation, transcriptomic characterization, and in vivo fate analyses, we found that p75NTR(+) precursors of human foreskin can be ascribed to the Schwann (CD56(+)) and perivascular (CD56(-)) cell lineages. Moreover, neural differentiation potential was restricted to the p75NTR(+)CD56(+) Schwann cells and mediated by SOX2 expression levels. Double-positive NPCs were similarly obtained from human cardiospheres, indicating that this phenomenon might be widespread.

  13. Neural-Competent Cells of Adult Human Dermis Belong to the Schwann Lineage

    PubMed Central

    Etxaniz, Usue; Pérez-San Vicente, Adrián; Gago-López, Nuria; García-Dominguez, Mario; Iribar, Haizea; Aduriz, Ariane; Pérez-López, Virginia; Burgoa, Izaskun; Irizar, Haritz; Muñoz-Culla, Maider; Vallejo-Illarramendi, Ainara; Leis, Olatz; Matheu, Ander; Martín, Angel G.; Otaegui, David; López-Mato, María Paz; Gutiérrez-Rivera, Araika; MacLellan, Robb; Izeta, Ander

    2014-01-01

    Summary Resident neural precursor cells (NPCs) have been reported for a number of adult tissues. Understanding their physiological function or, alternatively, their activation after tissue damage or in vitro manipulation remains an unsolved issue. Here, we investigated the source of human dermal NPCs in adult tissue. By following an unbiased, comprehensive approach employing cell-surface marker screening, cell separation, transcriptomic characterization, and in vivo fate analyses, we found that p75NTR+ precursors of human foreskin can be ascribed to the Schwann (CD56+) and perivascular (CD56−) cell lineages. Moreover, neural differentiation potential was restricted to the p75NTR+CD56+ Schwann cells and mediated by SOX2 expression levels. Double-positive NPCs were similarly obtained from human cardiospheres, indicating that this phenomenon might be widespread. PMID:25418723

  14. The response of the anterior striatum during adult human vocal learning.

    PubMed

    Simmonds, Anna J; Leech, Robert; Iverson, Paul; Wise, Richard J S

    2014-08-15

    Research on mammals predicts that the anterior striatum is a central component of human motor learning. However, because vocalizations in most mammals are innate, much of the neurobiology of human vocal learning has been inferred from studies on songbirds. Essential for song learning is a pathway, the homolog of mammalian cortical-basal ganglia "loops," which includes the avian striatum. The present functional magnetic resonance imaging (fMRI) study investigated adult human vocal learning, a skill that persists throughout life, albeit imperfectly given that late-acquired languages are spoken with an accent. Monolingual adult participants were scanned while repeating novel non-native words. After training on the pronunciation of half the words for 1 wk, participants underwent a second scan. During scanning there was no external feedback on performance. Activity declined sharply in left and right anterior striatum, both within and between scanning sessions, and this change was independent of training and performance. This indicates that adult speakers rapidly adapt to the novel articulatory movements, possibly by using motor sequences from their native speech to approximate those required for the novel speech sounds. Improved accuracy correlated only with activity in motor-sensory perisylvian cortex. We propose that future studies on vocal learning, using different behavioral and pharmacological manipulations, will provide insights into adult striatal plasticity and its potential for modification in both educational and clinical contexts.

  15. HMGA2 Moderately Increases Fetal Hemoglobin Expression in Human Adult Erythroblasts

    PubMed Central

    de Vasconcellos, Jaira F.; Lee, Y. Terry; Byrnes, Colleen; Tumburu, Laxminath; Rabel, Antoinette; Miller, Jeffery L.

    2016-01-01

    Induction of fetal hemoglobin (HbF) has therapeutic importance for patients with beta-hemoglobin disorders. Previous studies showed that let-7 microRNAs (miRNAs) are highly regulated in erythroid cells during the fetal-to-adult developmental transition, and that targeting let-7 mediated the up-regulation of HbF to greater than 30% of the total globin levels in human adult cultured erythroblasts. HMGA2 is a member of the high-mobility group A family of proteins and a validated target of the let-7 family of miRNAs. Here we investigate whether expression of HMGA2 directly regulates fetal hemoglobin in adult erythroblasts. Let-7 resistant HMGA2 expression was studied after lentiviral transduction of CD34(+) cells. The transgene was regulated by the erythroid-specific gene promoter region of the human SPTA1 gene (HMGA2-OE). HMGA2-OE caused significant increases in gamma-globin mRNA expression and HbF to around 16% of the total hemoglobin levels compared to matched control transductions. Interestingly, no significant changes in KLF1, SOX6, GATA1, ZBTB7A and BCL11A mRNA levels were observed. Overall, our data suggest that expression of HMGA2, a downstream target of let-7 miRNAs, causes moderately increased gamma-globin gene and protein expression in adult human erythroblasts. PMID:27861570

  16. The response of the anterior striatum during adult human vocal learning

    PubMed Central

    Leech, Robert; Iverson, Paul; Wise, Richard J. S.

    2014-01-01

    Research on mammals predicts that the anterior striatum is a central component of human motor learning. However, because vocalizations in most mammals are innate, much of the neurobiology of human vocal learning has been inferred from studies on songbirds. Essential for song learning is a pathway, the homolog of mammalian cortical-basal ganglia “loops,” which includes the avian striatum. The present functional magnetic resonance imaging (fMRI) study investigated adult human vocal learning, a skill that persists throughout life, albeit imperfectly given that late-acquired languages are spoken with an accent. Monolingual adult participants were scanned while repeating novel non-native words. After training on the pronunciation of half the words for 1 wk, participants underwent a second scan. During scanning there was no external feedback on performance. Activity declined sharply in left and right anterior striatum, both within and between scanning sessions, and this change was independent of training and performance. This indicates that adult speakers rapidly adapt to the novel articulatory movements, possibly by using motor sequences from their native speech to approximate those required for the novel speech sounds. Improved accuracy correlated only with activity in motor-sensory perisylvian cortex. We propose that future studies on vocal learning, using different behavioral and pharmacological manipulations, will provide insights into adult striatal plasticity and its potential for modification in both educational and clinical contexts. PMID:24805076

  17. Predictions of ozone absorption in human lungs from newborn to adult

    SciTech Connect

    Overton, J.H.; Graham, R.C. )

    1989-01-01

    Although children are an important human population, dosimetry models for gases have been used to predict absorption mainly in laboratory animals and adult humans. To correct this omission, we have used several sources of data on age-dependent lower respiratory tract (LRT) volumes, age-dependent airway dimensions, a model of the adult tracheobronchial region, and a model of the adult acinus to construct theoretical LRT lung models for humans from birth to adulthood. An ozone (O3) dosimetry model was then used to estimate the regional and local uptake of O3 in the (theoretical) LRT of children and adults. For sedentary or quiet breathing, the LRT distribution of absorbed O3, the percent uptake (84 to 88%) and the centriacinar O3 tissue dose are not very sensitive to age. For maximal work during exercise, predicted LRT uptakes range from 87 to 93%, and the regional percent uptakes are more dependent on age than during quiet breathing. In general, the total quantity of O3 absorbed per minute increases with age. Regardless of age and state of breathing, the largest tissue dose of O3 is predicted to occur in the centriacinar region, where many animal studies show the maximal morphological damage from O3.

  18. Neuroscience of human social interactions and adult attachment style

    PubMed Central

    Vrtička, Pascal; Vuilleumier, Patrik

    2012-01-01

    attachment insecurity and particularly anxiety. Emotion regulation strategies such as reappraisal or suppression of social emotions are also differentially modulated by attachment style. This research does not only help better understand the neural underpinnings of human social behavior, but also provides important insights on psychopathological conditions where attachment dysregulation is likely to play an important (causal) role. PMID:22822396

  19. Human Centred Design Considerations for Connected Health Devices for the Older Adult

    PubMed Central

    Harte, Richard P.; Glynn, Liam G.; Broderick, Barry J.; Rodriguez-Molinero, Alejandro; Baker, Paul M. A.; McGuiness, Bernadette; O’Sullivan, Leonard; Diaz, Marta; Quinlan, Leo R.; ÓLaighin, Gearóid

    2014-01-01

    Connected health devices are generally designed for unsupervised use, by non-healthcare professionals, facilitating independent control of the individuals own healthcare. Older adults are major users of such devices and are a population significantly increasing in size. This group presents challenges due to the wide spectrum of capabilities and attitudes towards technology. The fit between capabilities of the user and demands of the device can be optimised in a process called Human Centred Design. Here we review examples of some connected health devices chosen by random selection, assess older adult known capabilities and attitudes and finally make analytical recommendations for design approaches and design specifications. PMID:25563225

  20. Ultrastructural evidence of exosome secretion by progenitor cells in adult mouse myocardium and adult human cardiospheres.

    PubMed

    Barile, Lucio; Gherghiceanu, Mihaela; Popescu, Laurentiu M; Moccetti, Tiziano; Vassalli, Giuseppe

    2012-01-01

    The demonstration of beneficial effects of cell therapy despite the persistence of only few transplanted cells in vivo suggests secreted factors may be the active component of this treatment. This so-called paracrine hypothesis is supported by observations that culture media conditioned by progenitor cells contain growth factors that mediate proangiogenic and cytoprotective effects. Cardiac progenitor cells in semi-suspension culture form spherical clusters (cardiospheres) that deliver paracrine signals to neighboring cells. A key component of paracrine secretion is exosomes, membrane vesicles that are stored intracellularly in endosomal compartments and are secreted when these structures fuse with the cell plasma membrane. Exosomes have been identified as the active component of proangiogenic effects of bone marrow CD34⁺ stem cells in mice and the regenerative effects of embryonic mesenchymal stem cells in infarcted hearts in pigs and mice. Here, we provide electron microscopic evidence of exosome secretion by progenitor cells in mouse myocardium and human cardiospheres. Exosomes are emerging as an attractive vector of paracrine signals delivered by progenitor cells. They can be stored as an "off-the-shelf" product. As such, exosomes have the potential for circumventing many of the limitations of viable cells for therapeutic applications in regenerative medicine.

  1. 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)

  2. 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.

  3. Binding of furosemide to albumin isolated from human fetal and adult serum.

    PubMed

    Viani, A; Cappiello, M; Silvestri, D; Pacifici, G M

    1991-01-01

    Albumin was isolated from pooled fetal serum from 58 placentas obtained at normal delivery at term and from pooled adult plasma from 8 individuals. Albumin isolation was carried out by means of PEG precipitation followed by ion-exchange chromatography on DEAE-Sephadex A 50 and then on SP-Sephadex C 50. The electrophoresis on SDS-polyacrylamide gels showed only one spot that comigrated with commercial human albumin. Binding to albumin was measured by equilibrium dialysis of an aliquot of albumin solution (0.7 ml) against the same volume of 0.13 M sodium orthophosphate buffer (pH 7.4). At a total concentration of 2 micrograms/ml (therapeutic range), the unbound fraction of furosemide was 2.71% (fetal albumin) and 2.51% (adult albumin). Two classes of binding sites for furosemide were observed in fetal and adult albumin. The number of binding sites (moles of furosemide per mole of albumin) was 1.22 (fetal albumin) and 1.58 (adult albumin) for the high-affinity site and 2.97 (fetal albumin) and 3.25 (adult albumin) for the low-affinity site. The association constants (M-1) were 3.1 X 10(4) (fetal albumin) and 2.6 X 10(4) (adult albumin) for the high-affinity set of sites and 0.83 X 10(4) (fetal albumin) and 1.0 X 10(4) (adult albumin) low-affinity site. The displacement of furosemide from albumin was studied with therapeutic concentrations of several drugs. Valproic acid, salicylic acid, azapropazone and tolbutamide had the highest displacing effects which were significantly higher with fetal than with adult albumin.

  4. 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.

  5. Greater addition of neurons to the olfactory bulb than to the cerebral cortex of eulipotyphlans but not rodents, afrotherians or primates

    PubMed Central

    Ribeiro, Pedro F. M.; Manger, Paul R.; Catania, Kenneth C.; Kaas, Jon H.; Herculano-Houzel, Suzana

    2014-01-01

    The olfactory bulb is an evolutionarily old structure that antedates the appearance of a six-layered mammalian cerebral cortex. As such, the neuronal scaling rules that apply to scaling the mass of the olfactory bulb as a function of its number of neurons might be shared across mammalian groups, as we have found to be the case for the ensemble of non-cortical, non-cerebellar brain structures. Alternatively, the neuronal scaling rules that apply to the olfactory bulb might be distinct in those mammals that rely heavily on olfaction. The group previously referred to as Insectivora includes small mammals, some of which are now placed in Afrotheria, a base group in mammalian radiation, and others in Eulipotyphla, a group derived later, at the base of Laurasiatheria. Here we show that the neuronal scaling rules that apply to building the olfactory bulb differ across eulipotyphlans and other mammals such that eulipotyphlans have more neurons concentrated in an olfactory bulb of similar size than afrotherians, glires and primates. Most strikingly, while the cerebral cortex gains neurons at a faster pace than the olfactory bulb in glires, and afrotherians follow this trend, it is the olfactory bulb that gains neurons at a faster pace than the cerebral cortex in eulipotyphlans, which contradicts the common view that the cerebral cortex is the fastest expanding structure in brain evolution. Our findings emphasize the importance of not using brain structure size as a proxy for numbers of neurons across mammalian orders, and are consistent with the notion that different selective pressures have acted upon the olfactory system of eulipotyphlans, glires and primates, with eulipotyphlans relying more on olfaction for their behavior than glires and primates. Surprisingly, however, the neuronal scaling rules for primates predict that the human olfactory bulb has as many neurons as the larger eulipotyphlan olfactory bulbs, which questions the classification of humans as microsmatic

  6. 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.

  7. CB1 cannabinoid receptor enrichment in the ependymal region of the adult human spinal cord

    PubMed Central

    Paniagua-Torija, Beatriz; Arevalo-Martin, Angel; Ferrer, Isidro; Molina-Holgado, Eduardo; Garcia-Ovejero, Daniel

    2015-01-01

    Cannabinoids are involved in the regulation of neural stem cell biology and their receptors are expressed in the neurogenic niches of adult rodents. In the spinal cord of rats and mice, neural stem cells can be found in the ependymal region, surrounding the central canal, but there is evidence that this region is largely different in adult humans: lacks a patent canal and presents perivascular pseudorosettes, typically found in low grade ependymomas. Using Laser Capture Microdissection, Taqman gene expression assays and immunohistochemistry, we have studied the expression of endocannabinoid system components (receptors and enzymes) at the human spinal cord ependymal region. We observe that ependymal region is enriched in CB1 cannabinoid receptor, due to high CB1 expression in GFAP+ astrocytic domains. However, in human spinal cord levels that retain central canal patency we found ependymal cells with high CB1 expression, equivalent to the CB1HIGH cell subpopulation described in rodents. Our results support the existence of ependymal CB1HIGH cells across species, and may encourage further studies on this subpopulation, although only in cases when central canal is patent. In the adult human ependyma, which usually shows central canal absence, CB1 may play a different role by modulating astrocyte functions. PMID:26634814

  8. CB1 cannabinoid receptor enrichment in the ependymal region of the adult human spinal cord.

    PubMed

    Paniagua-Torija, Beatriz; Arevalo-Martin, Angel; Ferrer, Isidro; Molina-Holgado, Eduardo; Garcia-Ovejero, Daniel

    2015-12-04

    Cannabinoids are involved in the regulation of neural stem cell biology and their receptors are expressed in the neurogenic niches of adult rodents. In the spinal cord of rats and mice, neural stem cells can be found in the ependymal region, surrounding the central canal, but there is evidence that this region is largely different in adult humans: lacks a patent canal and presents perivascular pseudorosettes, typically found in low grade ependymomas. Using Laser Capture Microdissection, Taqman gene expression assays and immunohistochemistry, we have studied the expression of endocannabinoid system components (receptors and enzymes) at the human spinal cord ependymal region. We observe that ependymal region is enriched in CB1 cannabinoid receptor, due to high CB1 expression in GFAP+ astrocytic domains. However, in human spinal cord levels that retain central canal patency we found ependymal cells with high CB1 expression, equivalent to the CB1(HIGH) cell subpopulation described in rodents. Our results support the existence of ependymal CB1(HIGH) cells across species, and may encourage further studies on this subpopulation, although only in cases when central canal is patent. In the adult human ependyma, which usually shows central canal absence, CB1 may play a different role by modulating astrocyte functions.

  9. 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…

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. PET imaging of neurogenic activity in the adult brain: Toward in vivo imaging of human neurogenesis.

    PubMed

    Tamura, Yasuhisa; Kataoka, Yosky

    2017-01-01

    Neural stem cells are present in 2 neurogenic regions, the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG), and continue to generate new neurons throughout life. Adult hippocampal neurogenesis is linked to a variety of psychiatric disorders such as depression and anxiety, and to the therapeutic effects of antidepressants, as well as learning and memory. In vivo imaging for hippocampal neurogenic activity may be used to diagnose psychiatric disorders and evaluate the therapeutic efficacy of antidepressants. However, these imaging techniques remain to be established until now. Recently, we established a quantitative positron emission tomography (PET) imaging technique for neurogenic activity in the adult brain with 3'-deoxy-3'-[(18)F]fluoro-L-thymidine ([(18)F]FLT) and probenecid, a drug transporter inhibitor in blood-brain barrier. Moreover, we showed that this PET imaging technique can monitor alterations in neurogenic activity in the hippocampus of adult rats with depression and following treatment with an antidepressant. This PET imaging method may assist in diagnosing depression and in monitoring the therapeutic efficacy of antidepressants. In this commentary, we discuss the possibility of in vivo PET imaging for neurogenic activity in adult non-human primates and humans.

  2. Origin of germ cells and formation of new primary follicles in adult human ovaries

    PubMed Central

    Bukovsky, Antonin; Caudle, Michael R; Svetlikova, Marta; Upadhyaya, Nirmala B

    2004-01-01

    Recent reports indicate that functional mouse oocytes and sperm can be derived in vitro from somatic cell lines. We hypothesize that in adult human ovaries, mesenchymal cells in the tunica albuginea (TA) are bipotent progenitors with a commitment for both primitive granulosa and germ cells. We investigated ovaries of twelve adult women (mean age 32.8 ± 4.1 SD, range 27–38 years) by single, double, and triple color immunohistochemistry. We show that cytokeratin (CK)+ mesenchymal cells in ovarian TA differentiate into surface epithelium (SE) cells by a mesenchymal-epithelial transition. Segments of SE directly associated with ovarian cortex are overgrown by TA, forming solid epithelial cords, which fragment into small (20 micron) epithelial nests descending into the lower ovarian cortex, before assembling with zona pellucida (ZP)+ oocytes. Germ cells can originate from SE cells which cover the TA. Small (10 micron) germ-like cells showing PS1 meiotically expressed oocyte carbohydrate protein are derived from SE cells via asymmetric division. They show nuclear MAPK immunoexpression, subsequently divide symmetrically, and enter adjacent cortical vessels. During vascular transport, the putative germ cells increase to oocyte size, and are picked-up by epithelial nests associated with the vessels. During follicle formation, extensions of granulosa cells enter the oocyte cytoplasm, forming a single paranuclear CK+ Balbiani body supplying all the mitochondria of the oocyte. In the ovarian medulla, occasional vessels show an accumulation of ZP+ oocytes (25–30 microns) or their remnants, suggesting that some oocytes degenerate. In contrast to males, adult human female gonads do not preserve germline type stem cells. This study expands our previous observations on the formation of germ cells in adult human ovaries. Differentiation of primitive granulosa and germ cells from the bipotent mesenchymal cell precursors of TA in adult human ovaries represents a most

  3. A seroprevalence survey for human immunodeficiency virus antibody in mentally retarded adults.

    PubMed

    Pincus, S H; Schoenbaum, E E; Webber, M

    1990-03-01

    The prevalence of human immunodeficiency virus (HIV) infection among adults who are mentally retarded is not known. Policies for those in residential settings are being established despite incomplete information. Knowledge regarding HIV seroprevalence would enable administrators to make more effective policy decisions concerning testing and HIV prevention. Discarded sera from mentally retarded adults were anonymously tested for HIV antibody. Sera were collected from a health facility in Westchester County, NY, that provides care to developmentally disabled adults. After identifications were removed, sera were coded and linked to demographic and clinical variables from hospital and laboratory records. Sera came from individuals living in both institutional and less restrictive community settings in metropolitan New York City and more distant locations in New York State, all of whom were seen by the above facility. No HIV antibody was detected in sera from 241 mentally retarded adults. This study suggests that the prevalence of HIV antibody in mentally retarded adults is not high. Mandatory screening programs may not be appropriate for these individuals. Monies might be better spent on educational programs directed at AIDS prevention, and further development of ethical and safe policies for those who are mentally retarded.

  4. A Comparison of Pure Tone Auditory Thresholds in Human Infants and Adults.

    PubMed

    Sinnott, Joan M; Pisoni, David B; Aslin, Richard N

    1983-01-01

    Pure tone auditory thresholds for frequencies from .250 to 8.0 kHz were obtained from 277-to-11-month-old human infants and nine adults using a go-no-go operant head-turning technique combined with an adaptive staircase (tracking) discrimination procedure. New methods were devised for maintaining infants under stimulus control during threshold testing through the use of randomly interleaved "probe" and "catch" trials. Reliable threshold data were obtained from every infant studied, and identical threshold criteria were applied to infants and adults alike. Although infant thresholds were 17-27 dB higher than those of adults, infant inter-subject variability was no greater than that of adults. Adult audiograms were nearly flat between frequencies of .500 and 8.0 kHz with sensitivity ranging between 7 and 14 dB SPL. Infant audiograms were flat between frequencies of .500 and 4.0 kHz, with sensitivity ranging between 30 and 36 dB SPL. The most sensitive frequency for infants was 8.0 kHz (25 dB SPL).

  5. 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.

  6. THE OLFACTORY NERVE HAS A ROLE IN THE BODY TEMPERATURE AND BRAIN CYTOKINE RESPONSES TO INFLUENZA VIRUS

    PubMed Central

    Leyva-Grado, Victor H.; Churchill, Lynn; Harding, Joseph; Krueger, James M.

    2009-01-01

    Mouse-adapted human influenza virus is detectable in the olfactory bulbs of mice within hours after intranasal challenge and is associated with enhanced local cytokine mRNA and protein levels. To determine whether signals from the olfactory nerve influence the unfolding of the acute phase response (APR), we surgically transected the olfactory nerve in mice prior to influenza infection. We then compared the responses of olfactory nerve-transected (ONT) mice to those recorded in sham-operated control mice using measurements of body temperature, food intake, body weight, locomotor activity and immunohistochemistry for cytokines and the viral antigen, H1N1. ONT did not change baseline body temperature (Tb); however, the onset of virus-induced hypothermia was delayed for about 13 h in the ONT mice. Locomotor activity, food intake and body weights of the two groups were similar. At 15 h post-challenge fewer viral antigen-immunoreactive (IR) cells were observed in the olfactory bulb (OB) of ONT mice compared to sham controls. The number of tumor necrosis factor alpha (TNFα)- and interleukin 1 beta (IL1β)-IR cells in ONT mice was also reduced in the OB and other interconnected regions in the brain compared to sham controls. These results suggest that the olfactory nerve pathway is important for the initial pathogenesis of the influenza-induced APR. PMID:19836444

  7. Reduced nasal transport of insulin-like growth factor-1 to the mouse cerebrum with olfactory bulb resection.

    PubMed

    Shiga, Hideaki; Nagaoka, Mikiya; Washiyama, Kohshin; Yamamoto, Junpei; Yamada, Kentaro; Noda, Takuya; Harita, Masayuki; Amano, Ryohei; Miwa, Takaki

    2014-09-01

    Although the olfactory nerve is involved in nasal transport of insulin-like growth factor-1 (IGF-1) to the brain, to our knowledge there have been no direct assessments of the effects of olfactory nerve damage on this transport. To determine whether olfactory bulb resection resulted in reduced transport of nasally administered human recombinant IGF-1 (hIGF-1) to the cerebrum, we measured the uptake of nasally administered iodine-125 hIGF-1 ((125)I-hIGF-1) in the cerebrum as a percentage of that in the blood in male ICR mice subjected to left olfactory bulb resection (model mice) and in sham-operated male ICR mice (control mice). Phosphorylated extracellular signal-regulated kinase (ERK) 1/2 (Thr202/Tyr204)/(Thr185/Tyr187) as a percentage of total ERK 1/2 in the left cerebrum was also assessed by using enzyme-linked immunosorbent assay after nasal administration of hIGF-1. Uptake of nasally administered (125)I-hIGF-1 in the cerebrum as a percentage of that in the blood was significantly lower in the model group than in the control group 30min after nasal administration of hIGF-1. Unilateral olfactory bulb resection prevented nasally administered hIGF-1 from increasing the phosphorylation of ERK 1/2 in the mouse cerebrum in vivo. These findings suggest that olfactory bulb damage reduces nasal transport of hIGF-1 to the brain in vivo.

  8. PAN-811 inhibits oxidative stress-induced cell death of human Alzheimer's disease-derived and age-matched olfactory neuroepithelial cells via suppression of intracellular reactive oxygen species.

    PubMed

    Nelson, Valery M; Dancik, Chantée M; Pan, Weiying; Jiang, Zhi-Gang; Lebowitz, Michael S; Ghanbari, Hossein A

    2009-01-01

    Oxidative stress plays a significant role in neurotoxicity associated with a variety of neurodegenerative diseases including Alzheimer's disease (AD). Increased oxidative stress has been shown to be a prominent and early feature of vulnerable neurons in AD. Olfactory neuroepithelial cells are affected at an early stage. Exposure to oxidative stress induces the accumulation of intracellular reactive oxygen species (ROS), which in turn causes cell damage in the form of protein, lipid, and DNA oxidations. Elevated ROS levels are also associated with increased deposition of amyloid-beta and formation of senile plaques, a hallmark of the AD brain. If enhanced ROS exceeds the basal level of cellular protective mechanisms, oxidative damage and cell death will result. Therefore, substances that can reduce oxidative stress are sought as potential drug candidates for treatment or preventative therapy of neurodegenerative diseases such as AD. PAN-811, also known as 3-aminopyridine-2-carboxaldehyde thiosemicarbazone or Triapine, is a small lipophilic compound that is currently being investigated in several Phase II clinical trials for cancer therapy due to its inhibition of ribonucleotide reductase activity. Here we show PAN-811 to be effective in preventing or reducing ROS accumulation and the resulting oxidative damages in both AD-derived and age-matched olfactory neuroepithelial cells.

  9. Isolation, Characterization, and Differentiation of Progenitor Cells from Human Adult Adrenal Medulla

    PubMed Central

    Santana, Magda M.; Chung, Kuei-Fang; Vukicevic, Vladimir; Rosmaninho-Salgado, Joana; Kanczkowski, Waldemar; Cortez, Vera; Hackmann, Karl; Bastos, Carlos A.; Mota, Alfredo; Schrock, Evelin; Bornstein, Stefan R.; Cavadas, Cláudia

    2012-01-01

    Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persists, and recently, we established a method to isolate and differentiate these progenitor cells from adult bovine adrenals. However, no studies have elucidated the existence of adrenal progenitor cells within the human adrenal medulla. Here we describe the isolation, characterization, and differentiation of chromaffin progenitor cells obtained from adult human adrenals. Human chromaffin progenitor cells were cultured in low-attachment conditions for 10–12 days as free-floating spheres in the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor. These primary human chromosphere cultures were characterized by the expression of several progenitor markers, including nestin, CD133, Notch1, nerve growth factor receptor, Snai2, Sox9, Sox10, Phox2b, and Ascl1 on the molecular level and of Sox9 on the immunohistochemical level. In opposition, phenylethanolamine N-methyltransferase (PNMT), a marker for differentiated chromaffin cells, significantly decreased after 12 days in culture. Moreover, when plated on poly-l-lysine/laminin-coated slides in the presence of FGF-2, human chromaffin progenitor cells were able to differentiate into two distinct neuron-like cell types, tyrosine hydroxylase (TH)+/β-3-tubulin+ cells and TH−/β-3-tubulin+ cells, and into chromaffin cells (TH+/PNMT+). This study demonstrates the presence of progenitor cells in the human adrenal medulla and reveals their potential use in regenerative medicine, especially in the treatment of neuroendocrine and neurodegenerative diseases. PMID:23197690

  10. Isolation, characterization, and differentiation of progenitor cells from human adult adrenal medulla.

    PubMed

    Santana, Magda M; Chung, Kuei-Fang; Vukicevic, Vladimir; Rosmaninho-Salgado, Joana; Kanczkowski, Waldemar; Cortez, Vera; Hackmann, Klaus; Bastos, Carlos A; Mota, Alfredo; Schrock, Evelin; Bornstein, Stefan R; Cavadas, Cláudia; Ehrhart-Bornstein, Monika

    2012-11-01

    Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persists, and recently, we established a method to isolate and differentiate these progenitor cells from adult bovine adrenals. However, no studies have elucidated the existence of adrenal progenitor cells within the human adrenal medulla. Here we describe the isolation, characterization, and differentiation of chromaffin progenitor cells obtained from adult human adrenals. Human chromaffin progenitor cells were cultured in low-attachment conditions for 10-12 days as free-floating spheres in the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor. These primary human chromosphere cultures were characterized by the expression of several progenitor markers, including nestin, CD133, Notch1, nerve growth factor receptor, Snai2, Sox9, Sox10, Phox2b, and Ascl1 on the molecular level and of Sox9 on the immunohistochemical level. In opposition, phenylethanolamine N-methyltransferase (PNMT), a marker for differentiated chromaffin cells, significantly decreased after 12 days in culture. Moreover, when plated on poly-l-lysine/laminin-coated slides in the presence of FGF-2, human chromaffin progenitor cells were able to differentiate into two distinct neuron-like cell types, tyrosine hydroxylase (TH)(+)/β-3-tubulin(+) cells and TH(-)/β-3-tubulin(+) cells, and into chromaffin cells (TH(+)/PNMT(+)). This study demonstrates the presence of progenitor cells in the human adrenal medulla and reveals their potential use in regenerative medicine, especially in the treatment of neuroendocrine and neurodegenerative diseases.

  11. Normalizing the environment recapitulates adult human immune traits in laboratory mice.

    PubMed

    Beura, Lalit K; Hamilton, Sara E; Bi, Kevin; Schenkel, Jason M; Odumade, Oludare A; Casey, Kerry A; Thompson, Emily A; Fraser, Kathryn A; Rosato, Pamela C; Filali-Mouhim, Ali; Sekaly, Rafick P; Jenkins, Marc K; Vezys, Vaiva; Haining, W Nicholas; Jameson, Stephen C; Masopust, David

    2016-04-28

    Our current understanding of immunology was largely defined in laboratory mice, partly because they are inbred and genetically homogeneous, can be genetically manipulated, allow kinetic tissue analyses to be carried out from the onset of disease, and permit the use of tractable disease models. Comparably reductionist experiments are neither technically nor ethically possible in humans. However, there is growing concern that laboratory mice do not reflect relevant aspects of the human immune system, which may account for failures to translate disease treatments from bench to bedside. Laboratory mice live in abnormally hygienic specific pathogen free (SPF) barrier facilities. Here we show that standard laboratory mouse husbandry has profound effects on the immune system and that environmental changes produce mice with immune systems closer to those of adult humans. Laboratory mice--like newborn, but not adult, humans--lack effector-differentiated and mucosally distributed memory T cells. These cell populations were present in free-living barn populations of feral mice and pet store mice with diverse microbial experience, and were induced in laboratory mice after co-housing with pet store mice, suggesting that the environment is involved in the induction of these cells. Altering the living conditions of mice profoundly affected the cellular composition of the innate and adaptive immune systems, resulted in global changes in blood cell gene expression to patterns that more closely reflected the immune signatures of adult humans rather than neonates, altered resistance to infection, and influenced T-cell differentiation in response to a de novo viral infection. These data highlight the effects of environment on the basal immune state and response to infection and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modelling immunological events in free-living organisms, including humans.

  12. Recapitulating adult human immune traits in laboratory mice by normalizing environment

    PubMed Central

    Beura, Lalit K.; Hamilton, Sara E.; Bi, Kevin; Schenkel, Jason M.; Odumade, Oludare A.; Casey, Kerry A.; Thompson, Emily A.; Fraser, Kathryn A.; Rosato, Pamela C.; Filali-Mouhim, Ali; Sekaly, Rafick P.; Jenkins, Marc K.; Vezys, Vaiva; Haining, W. Nicholas; Jameson, Stephen C.; Masopust, David

    2016-01-01

    Our current understanding of immunology was largely defined in laboratory mice because of experimental advantages including inbred homogeneity, tools for genetic manipulation, the ability to perform kinetic tissue analyses starting with the onset of disease, and tractable models. Comparably reductionist experiments are neither technically nor ethically possible in humans. Despite revealing many fundamental principals of immunology, there is growing concern that mice fail to capture relevant aspects of the human immune system, which may account for failures to translate disease treatments from bench to bedside1–8. Laboratory mice live in abnormally hygienic “specific pathogen free” (SPF) barrier facilities. Here we show that the standard practice of laboratory mouse husbandry has profound effects on the immune system and that environmental changes result in better recapitulation of features of adult humans. Laboratory mice lack effector-differentiated and mucosally distributed memory T cells, which more closely resembles neonatal than adult humans. These cell populations were present in free-living barn populations of feral mice, pet store mice with diverse microbial experience, and were induced in laboratory mice after co-housing with pet store mice, suggesting a role for environment. Consequences of altering mouse housing profoundly impacted the cellular composition of the innate and adaptive immune system and resulted in global changes in blood cell gene expression patterns that more closely aligned with immune signatures of adult humans rather than neonates, altered the mouse’s resistance to infection, and impacted T cell differentiation to a de novo viral infection. These data highlight the impact of environment on the basal immune state and response to infection and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modeling immunological events in free-living organisms, including humans. PMID

  13. Adult human gingival epithelial cells as a source for whole-tooth bioengineering.

    PubMed

    Angelova Volponi, A; Kawasaki, M; Sharpe, P T

    2013-04-01

    Teeth develop from interactions between embryonic oral epithelium and neural-crest-derived mesenchyme. These cells can be separated into single-cell populations and recombined to form normal teeth, providing a basis for bioengineering new teeth if suitable, non-embryonic cell sources can be identified. We show here that cells can be isolated from adult human gingival tissue that can be expanded in vitro and, when combined with mouse embryonic tooth mesenchyme cells, form teeth. Teeth with developing roots can be produced from this cell combination following transplantation into renal capsules. These bioengineered teeth contain dentin and enamel with ameloblast-like cells and rests of Malassez of human origin.

  14. FGF2-induced effects on transcriptome associated with regeneration competence in adult human fibroblasts

    PubMed Central

    2013-01-01

    Background Adult human fibroblasts grown in low oxygen and with FGF2 supplementation have the capacity to tip the healing outcome of skeletal muscle injury – by favoring regeneration response in vivo over scar formation. Here, we compare the transcriptomes of control adult human dermal fibroblasts and induced regeneration-competent (iRC) fibroblasts to identify transcriptional changes that may be related to their regeneration competence. Results We identified a unique gene-expression profile that characterizes FGF2-induced iRC fibroblast phenotype. Significantly differentially expressed genes due to FGF2 treatment were identified and analyzed to determine overrepresented Gene Ontology terms. Genes belonging to extracellular matrix components, adhesion molecules, matrix remodelling, cytoskeleton, and cytokines were determined to be affected by FGF2 treatment. Conclusions Transcriptome analysis comparing control adult human fibroblasts with FGF2-treated fibroblasts identified functional groups of genes that reflect transcriptional changes potentially contributing to their regeneration competence. This comparative transcriptome analysis should contribute new insights into genes that characterize cells with greater regenerative potential. PMID:24066673

  15. Rapid Increase in Neural Conduction Time in the Adult Human Auditory Brainstem Following Sudden Unilateral Deafness.

    PubMed

    Maslin, M R D; Lloyd, S K; Rutherford, S; Freeman, S; King, A; Moore, D R; Munro, K J

    2015-10-01

    Individuals with sudden unilateral deafness offer a unique opportunity to study plasticity of the binaural auditory system in adult humans. Stimulation of the intact ear results in increased activity in the auditory cortex. However, there are no reports of changes at sub-cortical levels in humans. Therefore, the aim of the present study was to investigate changes in sub-cortical activity immediately before and after the onset of surgically induced unilateral deafness in adult humans. Click-evoked auditory brainstem responses (ABRs) to stimulation of the healthy ear were recorded from ten adults during the course of translabyrinthine surgery for the removal of a unilateral acoustic neuroma. This surgical technique always results in abrupt deafferentation of the affected ear. The results revealed a rapid (within minutes) reduction in latency of wave V (mean pre = 6.55 ms; mean post = 6.15 ms; p < 0.001). A latency reduction was also observed for wave III (mean pre = 4.40 ms; mean post = 4.13 ms; p < 0.001). These reductions in response latency are consistent with functional changes including disinhibition or/and more rapid intra-cellular signalling affecting binaurally sensitive neurons in the central auditory system. The results are highly relevant for improved understanding of putative physiological mechanisms underlying perceptual disorders such as tinnitus and hyperacusis.

  16. Long-term culture and functional characterization of follicular cells from adult normal human thyroids.

    PubMed Central

    Curcio, F; Ambesi-Impiombato, F S; Perrella, G; Coon, H G

    1994-01-01

    We have obtained long-term cultures of differentiated proliferating follicular cells from normal adult human thyroid glands. In vitro growth of such human cells has been sustained by a modified F-12 medium, supplemented with bovine hypothalamus and pituitary extracts and no added thyrotropin. Cultures have been expanded, cloned, frozen, successfully retrieved, and characterized. Functional characterization of these cells shows constitutive thyroglobulin production and release and thyrotropin-dependent adenosine 3',5'-cyclic monophosphate production, the latter apparently not associated with significant increases in DNA synthesis or cell proliferation. Genetic characterization of these cells by chromosome counting showed the normal diploid chromosome number. The ability to cultivate differentiated human thyroid follicular cells in long-term culture opens possibilities for investigating the transduction pathways of thyrotropin stimulation in normal and pathological human tissues, developing clinically relevant in vitro assays, and considering cellular and molecular therapies. Images PMID:8090760

  17. 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.

  18. 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

  19. 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.

  20. Moxidectin causes adult worm mortality of human lymphatic filarial parasite Brugia malayi in rodent models.

    PubMed

    Verma, Meenakshi; Pathak, Manisha; Shahab, Mohd; Singh, Kavita; Mitra, Kalyan; Misra-Bhattacharya, Shailja

    2014-12-01

    Moxidectin is a macrocyclic lactone belonging to milbemycin family closely related to ivermectin and is currently progressing towards Phase III clinical trial against human infection with the filaria Onchocerca volvulus (Leuckart, 1894). There is a single report on the microfilaricidal and embryostatic activity of moxidectin in case of the human lymphatic filarial parasite Brugia malayi (Brug, 1927) in Mastomys coucha (Smith) but without any adulticidal action. In the present study, the in vitro and in vivo antifilarial efficacy of moxidectin was evaluated on, B. malayi. In vitro moxidectin showed 100% reduction in adult female worm motility at 0.6 μM concentration within 7 days with 68% inhibition in the reduction of MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide dye) (which is used to detect viability of worms). A 50% inhibitory concentration (IC50) of moxidectin for adult female parasite was 0.242 μM, for male worm 0.186 μM and for microfilaria IC50 was 0.813 μM. In adult B. malayi-transplanted primary screening model (Meriones unguiculatus Milne-Edwards), moxidectin at a single optimal dose of 20 mg/kg by oral and subcutaneous route was found effective on both adult parasites and microfilariae. In secondary screening (M coucha, subcutaneously inoculated with infective larvae), moxidectin at the same dose by subcutaneous route brought about death of 49% of adult worms besides causing sterilisation in 54% of the recovered live female worms. The treated animals exhibited a continuous and sustained reduction in peripheral blood microfilaraemia throughout the observation period of 90 days. The mechanism of action of moxidectin is suggested to be similar to avermectins. The in silico studies were also designed to explore the interaction of moxidectin with glutamate-gated chloride channels of B. malayi. The docking results revealed a close interaction of moxidectin with various GluCl ligand sites of B. malayi.

  1. Urinary concentrations of parabens in Chinese young adults: implications for human exposure.

    PubMed

    Ma, Wan-Li; Wang, Lei; Guo, Ying; Liu, Li-Yan; Qi, Hong; Zhu, Ning-Zheng; Gao, Chong-Jing; Li, Yi-Fan; Kannan, Kurunthachalam

    2013-10-01

    Parabens are widely used as preservatives in foods, cosmetics, and pharmaceuticals. However, recent studies have indicated that high and systemic exposure to parabens can be harmful to human health. Although a few studies have reported urinary paraben levels in western countries, studies on paraben exposure in the Chinese population are limited. China is currently a major producer of parabens in the world. In this study, 109 urine samples collected from Chinese young adults (approximately 20 years old) were analyzed for five parabens (methyl-, ethyl-, propyl-, butyl-, and benzyl-parabens) by high-performance liquid chromatography-tandem mass spectrometry. Methyl-, propyl-, and ethyl-parabens were the three major paraben analogues found in all (100%) samples. The concentration of the sum of the five parabens ranged from 0.82 to 728 ng/mL with a geometric mean value of 17.4 ng/mL. Urinary concentration of parabens was 2-fold greater in females than in males. Based on the measured urinary concentrations, daily intake of parabens by the Chinese young adults was estimated and compared with those reported for United States adults. The estimated daily intakes (EDIurine) of parabens were 18.4 and 40.8 μg/kg bw/day for Chinese males and females, respectively, values that were lower than those reported for United States adults (74.7 μg/kg bw/day). Based on the reported concentrations of parabens in foods from China and the United States, the contribution of dietary intake to EDIurine was estimated to be 5.5, 2.6, and 0.42% for Chinese males, Chinese females, and United States adults, respectively, which indicates the significance of nondietary sources of parabens to human exposures.

  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. Epidemiologic, clinical, and virologic characteristics of human rhinovirus infection among otherwise healthy children and adults

    PubMed Central

    Chen, Wei-Ju; Arnold, John C.; Fairchok, Mary P.; Danaher, Patrick J.; McDonough, Erin A.; Blair, Patrick J.; Garcia, Josefina; Halsey, Eric S.; Schofield, Christina; Ottolini, Martin; Mor, Deepika; Ridoré, Michelande; Burgess, Timothy H.; Millar, Eugene V.

    2015-01-01

    Background Human rhinovirus (HRV) is a major cause of influenza-like illness (ILI) in adults and children. Differences in disease severity by HRV species have been described among hospitalized patients with underlying illness. Less is known about the clinical and virologic characteristics of HRV infection among otherwise healthy populations, particularly adults. Objectives To characterize molecular epidemiology of HRV and association between HRV species and clinical presentation and viral shedding. Study design Observational, prospective, facility-based study of ILI was conducted from February 2010 to April 2012. Collection of nasopharyngeal specimens, patient symptoms, and clinical information occurred on days 0, 3, 7, and 28. Patients recorded symptom severity daily for the first 7 days of illness in a symptom diary. HRV was identified by RT-PCR and genotyped for species determination. Cases who were co-infected with other viral respiratory pathogens were excluded from the analysis. We evaluated the associations between HRV species, clinical severity, and patterns of viral shedding. Results Eighty-four HRV cases were identified and their isolates genotyped. Of these, 62 (74%) were >18y. Fifty-four were HRV-A, 11 HRV-B, and 19 HRV-C. HRV-C infection was more common among children than adults (59% vs. 10%, P<0.001). Among adults, HRV-A was associated with higher severity of upper respiratory symptoms compared to HRV-B (P=0.02), but no such association was found in children. In addition, adults shed HRV-A significantly longer than HRV-C (Ptrend=0.01). Conclusions Among otherwise healthy adults with HRV infection, we observed species-specific differences in respiratory symptom severity and duration of viral shedding. PMID:25728083

  4. Comparison of human growth hormone products' cost in pediatric and adult patients. A budgetary impact model.

    PubMed

    Bazalo, Gary R; Joshi, Ashish V; Germak, John

    2007-09-01

    We assessed the economic impact to the United States payer of recombinant