Dissertations / Theses on the topic 'Olfactory epithelium'
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1
Schmachtenberg, Oliver. "Nitric oxide in the olfactory epithelium." [S.l.] : [s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=962820598.
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Vedin, Viktoria. "Molecular and functional anatomy of the mouse olfactory epithelium." Doctoral thesis, Umeå : Umeå universitet, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-868.
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3
Hsu, Pi-en. "Growth Factor Expression Associated With Regulation of Olfactory Neurogenesis." Thesis, Griffith University, 2005. http://hdl.handle.net/10072/367546.
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Olfactory neurons arise from the division of a stem cell in the basal area of the epithelium. After dividing asymmetrically and symmetrically, the stem cell gives rise to many immature olfactory receptor neurons that gradually differentiate into mature neurons as they migrate away from the basement membrane. The neurogenesis in the olfactory epithelium takes place throughout adult life, which makes the olfactory epithelium system a useful model with which to study the mechanisms that direct neural development.
Olfactory neurogenesis is highly regulated for the need of maintaining the equilibrium between the basal cell mitosis, cell death and cell survival in olfactory epithelium, for which many growth factors have been reported to play roles in regulating olfactory neurogenesis. Many reports observed the proliferative role of TGF and EGF in the olfactory neurogenesis and the expression of their receptors in horizontal basal cells, suggesting their signaling pathways for proliferation were mediated by a common receptor on the horizontal basal cells. FGF2 was reported to induce proliferation in a mouse embryo explant, a basal cell line, and in our laboratory, a basal cell culture. However, the target cells of FGF2 in the olfactory epithelium were not clear at the time of the research. TGF -2 was observed to stimulate differentiation in semi-dissociated olfactory tissues, in basal cell cultures and a basal cell line. Some of the receptors for TGF growth factors were found to be expressed in the olfactory epithelium but the identity of the target cells of TGF growth factors and the cells expressing them remained largely unknown. PDGF was observed in our laboratory to promote survival of immature neurons but there was no evidence to show the existence of its receptors on the immature neurons or to locate its source in the olfactory epithelium. This project aimed to identify and characterize the cells expressing TGF -2, PDGF and FGF growth factors and receptors in the olfactory epithelium using techniques of RT-PCR, immunohistochemistry, and in situ hybridisation. Our results have shown most members of TGF -2 superfamily were expressed in the olfactory epithelium in that TGF growth factors 1, 2, 3 and TGF receptor type 1, 2 and 3 were expressed extensively in superficially located basal cells, immature and mature neurons. FGF1 was expressed in olfactory epithelium. FGF2 and FGFr-1 were expressed by neurons and presumed globose basal cells. The supporting cells were like to express FGF2 mRNA. PDGF A and PDGF receptor had similar expression patterns in the olfactory epithelium. In support of previous studies, this project has provided in vivo evidence for the cells expressing the growth factors of importance and for the target cells these growth factors might act on. In addition to these, this project also investigated an unknown gene, 16b5, which was previously found to be unregulated by differentiation of an olfactory cell line, and has provided the in vivo evidence to support the finding.Thesis (Masters)
Master of Philosophy (MPhil)
School of Biomolecular and Biomedical Sciences
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4
Blomster, Linda. "Role of fractalkine/CX3CL1 signalling in the regenerating olfactory epithelium." Thesis, Högskolan i Kalmar, Naturvetenskapliga institutionen, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:hik:diva-905.
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The olfactory epithelium (OE) is a useful model to study neurogenesis because of the sustained ability for self-repair throughout adult life. The main aim of this study was to investigate putative neuroprotective roles of fractalkine/CX3CL1 signalling in the olfactory epithelium after experimentally-induced cell death and replacement of olfactory sensory neurons. Previous studies have shown that signalling through the fractalkine receptor, CX3CR1, can regulate neurotoxicity of monocyte-derived cells via suppression of pro-inflammatory cytokines production, i.e. IL-1β, TNF-α and IL-6. This is particularly interesting as the latter molecules contribute to a microenvironment that causes neuronal death and impaired neurogenesis. Real-time PCR (qPCR) was used to investigate differential expression of pro-inflammatory cytokines in wild-type and CX3CR1-deficient mice following olfactory bulbectomy. In addition, immunohistochemistry was used to investigate the influx of phagocytic macrophages into the OE and the extent of neurogenesis following injury. Increased numbers of intraepithelial macrophages were detected in the olfactory epithelium of CX3CR1-deficient mice after injury. Interestingly, expression levels of OMP (a marker for mature olfactory sensory neurons) were significantly reduced in CX3CR1-deficient mice after injury, which is indicative for increased neuronal death. The latter was confirmed by quantitative counts of OMP-positive neurons in tissue sections. The increased expression levels of both TNF-α and IL-6 that were detected in CX3CR1-deficient mice likely contributed to this aggravated neuronal death. The extent of neurogenesis was significantly decreased in the CX3CR1-deficient mice compared to the wild-type mice after bulbectomy. In summary, these results suggest that fractalkine signalling in the olfactory epithelium may have an important role in the regulation of macrophage responses to injury and maintenance of an environment that allows for functional repair.
5
Reed, C. J. "Studies of cytochrome P-450-dependent reactions in the olfactory epithelium." Thesis, University of Cambridge, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.374871.
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Wells, Karen Elizabeth. "Characterisation of the stem/precursor cells of the rat olfactory epithelium." Thesis, University of Cambridge, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.613198.
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7
Chamberlain, Mark Peter. "The toxicity of methyl iodide : in vivo and in vitro mechanistic studies in the rat nasal cavity and cerebellum." Thesis, Liverpool John Moores University, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244461.
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Kilgour, Joanne Dawn. "Development and validation of an in vitro rat nasal epithelial model for predicting respiratory tract toxicity." Thesis, Liverpool John Moores University, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.361508.
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9
Jang, Woochan. "The presence of fos-like immunoreactivity in neurons in the vomeronasal epithelium of mice /." free to MU campus, to others for purchase, 1997. http://wwwlib.umi.com/cr/mo/fullcit?p9842591.
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10
McCurdy, Richard D., and n/a. "Investigations of Olfactory Mucosa to Test the Neurodevelopmental Nature of Psychoses." Griffith University. School of Biomolecular and Biomedical Science, 2005. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20051121.133824.
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Evidence from various sources suggests that schizophrenia may result from altered brain development. The adult olfactory epithelium provides an available 'window' on neuronal development because new neurons are formed there throughout life. This thesis set out to test the neurodevelopmental hypothesis of psychotic disease. Two cell-based models, skin fibroblast and olfactory mucosa culture, were employed to investigate this hypothesis. In order to first demonstrate the utility of olfactory mucosa culture as a model of neurodevelopment, and to allow the candidate to gain proficiency in the culture of this tissue, an investigation of the mitogenic and differentiating properties of insulin-like growth factor-I within this system was undertaken. Insulin-like growth factor-I has multiple effects within the developing nervous system but its role in neurogenesis in the adult nervous system is less clear. The adult olfactory mucosa is a site of continuing neurogenesis that expresses insulin-like growth factor-I, its receptor, and its binding proteins. The action of insulin-like growth factor-I was assayed in several serum-free culture systems combined with bromodeoxyuridine labelling of proliferating cells and immunochemistry for specific cell types. Once proficiency in olfactory mucosa culture was gained, this model was applied to biopsied olfactory mucosa from schizophrenia and bipolar disorder patients in order to test the developmental parameters of adhesion, cell proliferation, and cell death in a neural tissue. It was previously shown that olfactory cultures from individuals with schizophrenia had increased cell proliferation and attached less frequently than cultures from healthy controls suggesting disrupted neurogenesis. An aim of this study was to replicate those observations in individuals with schizophrenia and and extend them to individuals with bipolar disorder. After completion of the cell and tissue culture assays, microarray analysis of these cell-based models was used to reveal gene expression differences present between patients and healthy controls. Microarray analysis is a complicated technique and the limited amounts of RNA that can be extracted from a single nasal biopsy further compounds this issue. In order to obtain enough material for microarray hybridization RNA samples underwent antisense amplification. Therefore, with the aim of allowing the candidate to gain proficiency in both these techniques prior to microarray analysis of olfactory biopsies from patients with schizophrenia and bipolar disorder, a pilot microarray study of cultured skin fibroblasts from schizophrenia patients and healthy controls was performed. The present findings show that insulin-like growth factor-I and its receptor were expressed by globose basal cells (the neuronal precursor), by neurons and by olfactory ensheathing cells, the special glia of the olfactory nerve. Insulin-like growth factor-I reduced the numbers of proliferating neuronal precursors, induced their differentiation into neurons, and promoted morphological differentiation of neurons. In contrast, this growth factor was mitogenic for olfactory ensheathing cells. The evidence suggests that insulin-like growth factor-I is an autocrine/paracrine signal that induces neuronal precursors to differentiate into olfactory sensory neurons and induces olfactory ensheathing cells to proliferate and that olfactory mucosa culture is valuable in modelling neurodevelopmental processes. When the olfactory musoca culture model was applied to patients with psychosis, a two-fold increase in proliferation of neural cells was found in schizophrenia compared to controls and bipolars. In bipolar cultures there was a 3-fold increase in cell death compared to controls and schizophrenia. Microarray analysis of cultured skin fibroblasts revealed differential expression of over 1000 genes between patients and controls. Inspection of the significant data showed alterations to gene expression between groups in the cell cycle, oxidative phosphorylation, TCA cycle and oxidative stress pathways. Gene expression in each of these pathways was predominately decreased in schizophrenia. Quantitative PCR analysis of selected differentially expressed genes involved with cell cycle regulation validated the increased expression of vitamin D receptor, and decreased expression of proliferating cell nuclear antigen and DEAD (Asp-GIu-Ala-Asp) box polypeptide 5 in skin fibroblasts from patients with schizophrenia. Microarray analysis of biopsied olfactory mucosa showed 146 and 139 differentially expressed genes in schizophrenia and bipolar disorder respectively, compared to controls. Consistent with increased mitosis in schizophrenia biopsy cultures three genes that function to positively influence cell cycle had increased expression. In the bipolar disorder group a dysregulation of the phosphatidylinositolsignalling pathway was seen; five genes that either directly function within or interact with this pathway had decreased expression. There is speculation that the therapeutic effect of psychotropic drugs acting upon this pathway in bipolar disorder involves reduction of neuronal cell death. Increased mitosis of neural cells has now been observed in two separate groups of schizophrenic patients indicating a robust finding. The use of fibroblast and olfactory mucosal tissue can be used to study biological and genetic aspects of neurodevelopment in living humans both with and without psychotic disease. Biopsied olfactory mucosa provides benefits over the use of autopsied material for study of psychotic disease because post-mortem duration and agonal factors that lead to tissue, protein and nucleic acid degradation are not an issue. This study provides evidence for a neurodevelopmental aetiology of schizophrenia and bipolar disorder acting at the level of cell cycle control. Subtle changes in the timing of cell cycle regulation could account for the brain pathologies observed in these diseases. Olfactory mucosa culture is a valuable model of neurodevelopmental processes.
11
McCurdy, Richard D. "Investigations of Olfactory Mucosa to Test the Neurodevelopmental Nature of Psychoses." Thesis, Griffith University, 2005. http://hdl.handle.net/10072/366460.
Full textAbstract:
Evidence from various sources suggests that schizophrenia may result from altered brain development. The adult olfactory epithelium provides an available 'window' on neuronal development because new neurons are formed there throughout life. This thesis set out to test the neurodevelopmental hypothesis of psychotic disease. Two cell-based models, skin fibroblast and olfactory mucosa culture, were employed to investigate this hypothesis. In order to first demonstrate the utility of olfactory mucosa culture as a model of neurodevelopment, and to allow the candidate to gain proficiency in the culture of this tissue, an investigation of the mitogenic and differentiating properties of insulin-like growth factor-I within this system was undertaken. Insulin-like growth factor-I has multiple effects within the developing nervous system but its role in neurogenesis in the adult nervous system is less clear. The adult olfactory mucosa is a site of continuing neurogenesis that expresses insulin-like growth factor-I, its receptor, and its binding proteins. The action of insulin-like growth factor-I was assayed in several serum-free culture systems combined with bromodeoxyuridine labelling of proliferating cells and immunochemistry for specific cell types. Once proficiency in olfactory mucosa culture was gained, this model was applied to biopsied olfactory mucosa from schizophrenia and bipolar disorder patients in order to test the developmental parameters of adhesion, cell proliferation, and cell death in a neural tissue. It was previously shown that olfactory cultures from individuals with schizophrenia had increased cell proliferation and attached less frequently than cultures from healthy controls suggesting disrupted neurogenesis. An aim of this study was to replicate those observations in individuals with schizophrenia and and extend them to individuals with bipolar disorder. After completion of the cell and tissue culture assays, microarray analysis of these cell-based models was used to reveal gene expression differences present between patients and healthy controls. Microarray analysis is a complicated technique and the limited amounts of RNA that can be extracted from a single nasal biopsy further compounds this issue. In order to obtain enough material for microarray hybridization RNA samples underwent antisense amplification. Therefore, with the aim of allowing the candidate to gain proficiency in both these techniques prior to microarray analysis of olfactory biopsies from patients with schizophrenia and bipolar disorder, a pilot microarray study of cultured skin fibroblasts from schizophrenia patients and healthy controls was performed. The present findings show that insulin-like growth factor-I and its receptor were expressed by globose basal cells (the neuronal precursor), by neurons and by olfactory ensheathing cells, the special glia of the olfactory nerve. Insulin-like growth factor-I reduced the numbers of proliferating neuronal precursors, induced their differentiation into neurons, and promoted morphological differentiation of neurons. In contrast, this growth factor was mitogenic for olfactory ensheathing cells. The evidence suggests that insulin-like growth factor-I is an autocrine/paracrine signal that induces neuronal precursors to differentiate into olfactory sensory neurons and induces olfactory ensheathing cells to proliferate and that olfactory mucosa culture is valuable in modelling neurodevelopmental processes. When the olfactory musoca culture model was applied to patients with psychosis, a two-fold increase in proliferation of neural cells was found in schizophrenia compared to controls and bipolars. In bipolar cultures there was a 3-fold increase in cell death compared to controls and schizophrenia. Microarray analysis of cultured skin fibroblasts revealed differential expression of over 1000 genes between patients and controls. Inspection of the significant data showed alterations to gene expression between groups in the cell cycle, oxidative phosphorylation, TCA cycle and oxidative stress pathways. Gene expression in each of these pathways was predominately decreased in schizophrenia. Quantitative PCR analysis of selected differentially expressed genes involved with cell cycle regulation validated the increased expression of vitamin D receptor, and decreased expression of proliferating cell nuclear antigen and DEAD (Asp-GIu-Ala-Asp) box polypeptide 5 in skin fibroblasts from patients with schizophrenia. Microarray analysis of biopsied olfactory mucosa showed 146 and 139 differentially expressed genes in schizophrenia and bipolar disorder respectively, compared to controls. Consistent with increased mitosis in schizophrenia biopsy cultures three genes that function to positively influence cell cycle had increased expression. In the bipolar disorder group a dysregulation of the phosphatidylinositolsignalling pathway was seen; five genes that either directly function within or interact with this pathway had decreased expression. There is speculation that the therapeutic effect of psychotropic drugs acting upon this pathway in bipolar disorder involves reduction of neuronal cell death. Increased mitosis of neural cells has now been observed in two separate groups of schizophrenic patients indicating a robust finding. The use of fibroblast and olfactory mucosal tissue can be used to study biological and genetic aspects of neurodevelopment in living humans both with and without psychotic disease. Biopsied olfactory mucosa provides benefits over the use of autopsied material for study of psychotic disease because post-mortem duration and agonal factors that lead to tissue, protein and nucleic acid degradation are not an issue. This study provides evidence for a neurodevelopmental aetiology of schizophrenia and bipolar disorder acting at the level of cell cycle control. Subtle changes in the timing of cell cycle regulation could account for the brain pathologies observed in these diseases. Olfactory mucosa culture is a valuable model of neurodevelopmental processes.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Biomedical Sciences
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12
Rieling, Janine Ann. "Sensory receptor neuron turnover in the olfactory epithelium of the snail, Achatina fulica : an autoradiographical study." Thesis, McGill University, 1985. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=63382.
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Gliem, Sebastian Verfasser], Detlev [Akademischer Betreuer] Schild, Ralf [Akademischer Betreuer] Heinrich, and Jürgen [Akademischer Betreuer] [Wienands. "Characterization of olfactory receptor gene expression in the olfactory epithelium of larval Xenopus laevis / Sebastian Gliem. Gutachter: Detlev Schild ; Ralf Heinrich ; Jürgen Wienands. Betreuer: Detlev Schild." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2011. http://d-nb.info/1042304998/34.
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Manzini, Ivan. "Diversity of transduction mechanisms in receptor neurons of the main olfactory epithelium in Xenopus laevis tadpoles." Doctoral thesis, [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=975110926.
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Joseph, Kyle Barnes. "Co-Localization of Basal and Proliferative Cells in the Murine Main Olfactory Epithelium and Vomeronasal Organ after Injury with Cyclophosphamide." ScholarWorks @ UVM, 2017. http://scholarworks.uvm.edu/graddis/684.
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ABSTRACT
In humans, advanced malignancies are often targeted with broad-spectrum cytotoxic drugs that engender several detrimental side effects, in addition to their primary usage for eradicating cancerous cells. One of the lesser-researched of these effects, histological distortion of the olfactory system impedes a patient's ability to smell, perceive flavor, and ultimately may interfere with their nutritional intake and recovery from chemotherapy. Recent studies have indicated that cytotoxic drugs can damage gustatory epithelia immediately following administration (Mukherjee & Delay, 2011, 2013). We sought to observe the histological effects that cyclophosphamide (CYP), one of the oldest and most popular alkylating antineoplastic agents, may have on the murine main olfactory epithelium (MOE) and vomeronasal organ (VNO). We utilized two immunohistochemical antibodies to label cells in the olfactory epithelia: anti-Ki67, a marker strictly associated with cell proliferation; and, anti-Keratin 5, a marker for the cytoskeleton of horizontal basal cells. Twenty-eight C57BL/6 mice were administered a single intraperitoneal injection of CYP (75 mg/kg), while 20 control mice were administered saline, all at approximately seven weeks of age. Mice were euthanized at days one, two, six, 14, 30, and 45 post injection; subsequently, they were perfused with 4% paraformaldehyde, decalcified, cryoprotected, cryosectioned, and incubated with anti-Ki67 and anti-Keratin 5 antibodies, sequentially. Quantification results by fluorescent imaging of labeled sections revealed a significant decrease in the number of proliferative cells in the MOE and VNO of CYP-injected mice within the first 10 days post injection, followed by a compensatory period of increased cell proliferation through day 45 post injection, compared to saline-injected mice. Co-localization of horizontal basal cells and proliferative cells in the MOE and VNO of CYP-injected mice was significantly amplified at approximately 14 and 45 days post injection, respectively, compared to saline-injected mice. Our results suggest that administration of CYP can rapidly depress the populations of proliferative cells in the murine MOE and VNO; consequently, horizontal basal cells may afford restoration of the proliferative cell populations in the murine MOE and VNO, 14 to 45 days post injection, respectively.
16
Edwards, Damian Andrew. "Nicotine as an odorant : a biochemical and electrophysiological study of receptors for nicotine in the olfactory epithelium of the rat." Thesis, University of Warwick, 1987. http://wrap.warwick.ac.uk/39023/.
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The results suggest that nicotine vapour stimulates an in vitro olfactory preparation in three strains of rat and two strains of mouse, in a manner similar to known odorants. Preliminary experiments also suggest that nicotine is an odorant for human subjects. In the rat, the electro-olfactogram (EOG) produced by nicotine is attenuated by superfusion of the olfactory mucosa with the lectin concanavalin A. This reduction is prevented by a-methyl-D-mannoside, suggesting. that there is a glyco-moiety associated with at least one olfactory receptor responding to nicotine. A concanavalin A induced change in EOG response with varying odorant concentration for several odorants, including nicotine, can be explained by a single concanavalin A sensitive olfactory receptor with a dissociation constant for odorant binding in the order of 100 nM. The results also show that hydrophilic odorants are poor stimulants for the olfactory epithelium, supporting the hypothesis that the interaction of an odorant with the olfactory receptors involves hydrophobic effects. Spatial variation in response to four odorants, including nicotine, by the rat olfactory epithelium can be explained by a mosaic of olfactory receptors of various types in the olfactory epithelium. This observation is consistent with current hypotheses of odour quality determination by the olfactory mucosa. Nicotine binding sites in olfactory and respiratory epithelia. Binding studies show that there are sites for 3H(-) nicotine in both olfactory and respiratory preparations, though these sites may not be the same in each tissue. The binding parameters for olfactory epithelium are Ko=695 nM and Bmax=8.24 pmol/mg protein (mean of two experiments at optimal binding conditions). The olfactory epithelium binding sites differ from binding sites for nicotine described elsewhere for brain (e.g. Ko values from 0.2-60 nM, Bmax values from 1-100 fmol/mg protein) and for liver (Ko=0.2 nM, Bmax=5 fmol/mg protein). Some of the 3H(-) nicotine binding may be to an olfactory receptor though more conclusive evidence is required to substantiate this.
17
Kolterud, Åsa. "The Role of Lhx2 During Organogenesis : - Analysis of the Hepatic, Hematopoietic and Olfactory Systems." Doctoral thesis, Umeå universitet, Molekylärbiologi (Teknat- och Medfak), 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-306.
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During embryonic development a variety of tissues and organs such as the lung, eye, and kidney are being formed. The generation of functional organs is regulated by reciprocal cell-cell interactions. Via the secretion of soluble molecules one type of cells affect the fate of their neighboring cells. A central issue in organogenesis is how a cell interprets such extrinsic signals and adopts a specific fate, and how the cell in response to this signal establishes reciprocal signaling. Transcription factors play a critical role in this process and my thesis focuses on the role of the LIM-homeodomain transcription factor, Lhx2, in the development of three different organ systems, the liver, the hematopoietic system and the olfactory system. The liver is formed from endoderm of the ventral foregut and mesenchyme of the septum transversum (st) and its development depends upon signaling interactions between these two tissues. As the liver becomes a distinct organ it is colonized by hematopoietic cells and serves as hematopoietic organ until birth. The fetal liver provides a microenvironment that supports the expansion of the entire hematopoietic system (HS) including the hematopoietic stem cells (HSCs). Liver development in Lhx2-/- embryos is disrupted leading to a lethal anemia due to insufficient support of hematopoiesis. To further investigate the role of Lhx2 in liver development I analyzed gene expression from the Lhx2 locus during liver development in wild-type and Lhx2-/- mice. Lhx2 is expressed in the liver associated st mesenchymal cells that become integrated in the liver and contribute to a subpopulation of hepatic stellate cells in adult liver. Lhx2 is not required for the formation of these mesenchymal cells, suggesting that the phenotype in Lhx2-/- livers is due to the presence of defective mesenchymal cells. The putative role of Lhx2 in the expansion of the HS was examined by introducing Lhx2 cDNA into embryonic stem cells differentiated in vitro. This approach allowed for the generation of immortalized multipotent hematopoietic progenitor cell (HPC) lines that share many characteristics with normal HSCs. The Lhx2-dependent generation of HSC-like cell lines suggests that Lhx2 plays a role in the maintenance and/or expansion of the HS. To isolate genes putatively linked to Lhx2 function, genes differentially expressed in the HPC lines were isolated using a cDNA subtraction approach. This allowed for the identification of a few genes putatively linked to Lhx2 function, as well as several stem cell-specific genes. The antagonist of Wnt signalling, Dickkopf-1 (Dkk-1), was identified in the former group of genes as it showed a similar expression pattern in the fetal liver, as that of Lhx2 and expression of Dkk-1 in fetal liver and in HPC lines appeared to be regulated by Lhx2. This suggests that Dkk-1 plays a role in liver development and/or HSC physiology during embryonic development. During development of the olfactory epithelium (OE) neuronal progenitors differentiate into mature olfactory sensory neurons (OSNs) that are individually specified into over a thousand different subpopulations, each expressing a unique odorant receptor (OR) gene. The expression of Lhx2 in olfactory neurons suggested a potential role for Lhx2 in the development of OSNs. To address this OE from Lhx2-/- and wild-type mice was compared. In the absence of functional Lhx2 neuronal differentiation was arrested prior to onset of OR expression. Lhx2 is thus required for the development of OSN progenitors into functional, individually specified OSNs. Thus, Lhx2 trigger a variety of cellular responses in different organ systems that play important roles in organ development in vivo and stem cell expansion in vitro.
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De, las Heras Rachel, and n/a. "Neuronal Differentiation: A Study Into Differential Gene Expression." Griffith University. School of Biomolecular and Biomedical Science, 2003. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20040225.161725.
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Neuronal differentiation encompasses an elaborate developmental program which until recently was difficult to study in vitro. The advent of several cell lines able to differentiate in culture proved to be the turning point for gaining an understanding of molecular neuroscience. In particular the olfactory epithelium provides an attractive tool with which to investigate fundamental questions relating to neuronal differentiation, as it displays a unique capacity to regenerate and to retain a neurogenetic potential from its genesis and throughout adult life. The coordinated regulation of gene expression is fundamental to the control of neuronal differentiation. In order to reveal active processes at the molecular level and to dissect key components of molecular pathways, differential gene expression studies provide a foundation for the elucidation of dynamic molecular mechanisms. This thesis identified genes involved in neuronal differentiation by utilising a clonal olfactory receptor neuronal cell line (OLF442). Gene expression levels were identified using differential display and oligonucleotide array technology before and after serum deprivation. Differential display revealed two kinases whose expression levels were elevated during the differentiation of OLF442, identified as focal adhesion kinase (FAK) related non-kinase (FRNK) and mammalian ste20 like (MST)2 kinase. Furthermore, analysis of the oligonucleotide array data confirmed the expression of genes involved in altering presentation of extracellular matrix molecules, in mediating cytoskeletal rearrangements, and in ceasing the cell cycle, supporting the use of OLF442 as a model for studying differentiation. The differentiation of OLF442 results from the synchronisation of multiple transduction cascades and cellular responses as evidenced by the microarray data. A protein that can synchronise such signalling is the non-receptor protein tyrosine kinase, FAK. Thus the finding of the endogenous FAK inhibitor FRNK by differential display was intriguing as there was no difference in the expression level of FAK induced by differentiation, contrasting that of FRNK. This induced FRNK expression was derived autonomously as it was not responsive to the caspase-3 inhibitor, DEVD-CHO. This is particularly pertinent since the primary role of FRNK is to act as an inhibitor of FAK by competing with its substrates and reducing the phosphorylation of both FAK and its associated proteins. Differential display also revealed the upregulation of another kinase, which had 90% homology with rat MST2 kinase within the 3' UTR. Both mouse MST2 kinase (sequence submitted to GenBank, accession number AY058922) and the closely related family member MST1 kinase were sequenced and cloned. Moreover, evidence to support an autonomously expressed carboxyl-terminal domain of MST2 kinase is presented in Chapter 3 and provides a unique way in which MST2 may regulate its own activity. To further understand the role of MST in neuronal differentiation, a series of stable OLF442 transfections (with mutant and wild-type MST constructs) were carried out. MST was localised with cytoplasmic structures that may represent actin stress fibres, indicating a potential cytoskeletal role during neuronal differentiation. This indicated that MST1 may play a role in the morphological processes involved in neuronal differentiation. The identification of two kinases by differential display provided the motivation to understand the cellular context of OLF442 and to determine the phosphorylation status of the mitogen-activated protein kinase (MAPK) signalling cascades. Differentiation of OLF442 induced high-level phosphorylation of a putative B-Raf isoform, MEK2 and ERK1/2. Interestingly, there was a switch between preferential phosphorylation of MEK1 in undifferentiated OLF442 to preferential phosphorylation of MEK2 following differentiation. SAPK/JNK was also phosphorylated, as was the transcription factor c-Jun, which is a common substrate of both the ERK and SAPK/JNK signalling modules. The mapping of the cellular context of differentiating OLF442 has identified a promising model of a novel MAPK module. This consists of FAK signalling through Rap1 to ERK providing sustained activation, which is buffered or terminated by the expression of the endogenous FAK inhibitor FRNK. Furthermore, MST kinase could potentially play a role in regulating the cytoskeletal re-arrangements that are necessary for neuronal differentiation. MST kinase may signal transiently via the SAPK pathway to provide concomitant activation of c-Jun that is required for neuronal differentiation. An understanding of the gene expression pattern of the normal neuronal differentiation program allows a greater understanding of potential developmental aberrations. This could provide an opportunity for therapies to be conceived, while understanding the complexity of neuronal determination could also provide opportunities for stem cell transplantation.
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De, las Heras Rachel. "Neuronal Differentiation: A Study Into Differential Gene Expression." Thesis, Griffith University, 2003. http://hdl.handle.net/10072/367735.
Full textAbstract:
Neuronal differentiation encompasses an elaborate developmental program which until recently was difficult to study in vitro. The advent of several cell lines able to differentiate in culture proved to be the turning point for gaining an understanding of molecular neuroscience. In particular the olfactory epithelium provides an attractive tool with which to investigate fundamental questions relating to neuronal differentiation, as it displays a unique capacity to regenerate and to retain a neurogenetic potential from its genesis and throughout adult life. The coordinated regulation of gene expression is fundamental to the control of neuronal differentiation. In order to reveal active processes at the molecular level and to dissect key components of molecular pathways, differential gene expression studies provide a foundation for the elucidation of dynamic molecular mechanisms. This thesis identified genes involved in neuronal differentiation by utilising a clonal olfactory receptor neuronal cell line (OLF442). Gene expression levels were identified using differential display and oligonucleotide array technology before and after serum deprivation. Differential display revealed two kinases whose expression levels were elevated during the differentiation of OLF442, identified as focal adhesion kinase (FAK) related non-kinase (FRNK) and mammalian ste20 like (MST)2 kinase. Furthermore, analysis of the oligonucleotide array data confirmed the expression of genes involved in altering presentation of extracellular matrix molecules, in mediating cytoskeletal rearrangements, and in ceasing the cell cycle, supporting the use of OLF442 as a model for studying differentiation. The differentiation of OLF442 results from the synchronisation of multiple transduction cascades and cellular responses as evidenced by the microarray data. A protein that can synchronise such signalling is the non-receptor protein tyrosine kinase, FAK. Thus the finding of the endogenous FAK inhibitor FRNK by differential display was intriguing as there was no difference in the expression level of FAK induced by differentiation, contrasting that of FRNK. This induced FRNK expression was derived autonomously as it was not responsive to the caspase-3 inhibitor, DEVD-CHO. This is particularly pertinent since the primary role of FRNK is to act as an inhibitor of FAK by competing with its substrates and reducing the phosphorylation of both FAK and its associated proteins. Differential display also revealed the upregulation of another kinase, which had 90% homology with rat MST2 kinase within the 3 ΠUTR. Both mouse MST2 kinase (sequence submitted to GenBank, accession number AY058922) and the closely related family member MST1 kinase were sequenced and cloned. Moreover, evidence to support an autonomously expressed carboxyl-terminal domain of MST2 kinase is presented in Chapter 3 and provides a unique way in which MST2 may regulate its own activity. To further understand the role of MST in neuronal differentiation, a series of stable OLF442 transfections (with mutant and wild-type MST constructs) were carried out. MST was localised with cytoplasmic structures that may represent actin stress fibres, indicating a potential cytoskeletal role during neuronal differentiation. This indicated that MST1 may play a role in the morphological processes involved in neuronal differentiation. The identification of two kinases by differential display provided the motivation to understand the cellular context of OLF442 and to determine the phosphorylation status of the mitogen-activated protein kinase (MAPK) signalling cascades. Differentiation of OLF442 induced high-level phosphorylation of a putative B-Raf isoform, MEK2 and ERK1/2. Interestingly, there was a switch between preferential phosphorylation of MEK1 in undifferentiated OLF442 to preferential phosphorylation of MEK2 following differentiation. SAPK/JNK was also phosphorylated, as was the transcription factor c-Jun, which is a common substrate of both the ERK and SAPK/JNK signalling modules. The mapping of the cellular context of differentiating OLF442 has identified a promising model of a novel MAPK module. This consists of FAK signalling through Rap1 to ERK providing sustained activation, which is buffered or terminated by the expression of the endogenous FAK inhibitor FRNK. Furthermore, MST kinase could potentially play a role in regulating the cytoskeletal re-arrangements that are necessary for neuronal differentiation. MST kinase may signal transiently via the SAPK pathway to provide concomitant activation of c-Jun that is required for neuronal differentiation. An understanding of the gene expression pattern of the normal neuronal differentiation program allows a greater understanding of potential developmental aberrations. This could provide an opportunity for therapies to be conceived, while understanding the complexity of neuronal determination could also provide opportunities for stem cell transplantationThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Biomedical Sciences
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Girerd, Cédric. "Conception de robots à tubes concentriques et application à l'inspection des cellules olfactives." Thesis, Strasbourg, 2018. http://www.theses.fr/2018STRAD005/document.
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Ces travaux de thèse s’inscrivent dans le cadre du projet ANR NEMRO, visant à étudier le lien entre déficience olfactive et maladies neurodégénératives. A cet effet, une biopsie optique de l’épithélium olfactif doit être réalisée. Son accès est cependant impossible, aujourd’hui, avec les outils conventionnels. Pour résoudre ce problème, nous proposons l’utilisation d’un robot à tubes concentriques (RTC). Sa synthèse est réalisée à partir d’images médicales. Elle prend en compte les critères de stabilité, la variabilité inter-sujet, et est associée à un déploiement ALFI (A La File Indienne). Le dispositif étant porté par le sujet, il doit être léger et compact. Une séquence de déploiement spécifique simplifie alors l’unité d’actionnement, et une implémentation est réalisée par fabrication additive multimatériaux. L’évaluation préliminaire d’un déploiement ALFI et des éléments de technologie clés a permis de valider l’approche retenue dans le projet NEMRO, ainsi que sa faisabilitéThis PhD thesis is part of the ANR NEMRO project, whose goal is to study the hypothetical correlation between olfactory deficiency and neurodegenerative diseases. For this purpose, an optical biopsy of the olfactory epithelium must be performed. However, this area is not accessible today with conventional tools. To go beyond this limitation, we propose to investigate the use a concentric tube robot (CTR). Its synthesis is performed from medical images. It takes into account the stability criteria, inter-subject variability, and is associated to a FTL (Follow-The-Leader) deployment. As the device is mounted on the subject, it has to be compact and lightweight. Thus, a specific deployment sequence simplifies the actuation unit, and an implementation is proposed using multimaterial additive manufacturing. Preliminary evaluations of the FTL deployment capabilities and the key components of the device allowed to validate the approach chosen for the NEMRO project, and its feasibility
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Guo, Luzhi. "Ultrastructural characteristics of cultured embryonic mouse olfactory epithelial and bulb cells." Thesis, University of North Texas, 1991. https://digital.library.unt.edu/ark:/67531/metadc798462/.
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This laboratory is involved in physiological and histochemical studies of olfactory tissue grown in cell culture in an attempt to create an in vitro model of the olfactory system. The present study is an in-depth ultrastructural study of the morphology of cultured olfactory cells to determine the extent of similarities and differences between cultured tissues and the intact olfactory system in vivo.
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Molinas, Adrien. "Mise en évidence de transporteurs de la résistance pléiotropique dans la muqueuse olfactive et leur implication dans la réponse aux odorants chez les rongeurs." Phd thesis, Université de Bourgogne, 2011. http://tel.archives-ouvertes.fr/tel-00763536.
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La résistance pléiotropique (MDR) est une propriété de certaines cellules relative à la capacité de rejeter ou d'évacuer une très large variété de substances potentiellement toxiques. Les pompes à l'origine de ce rejet sont des protéines membranaires appartenant à la superfamille ABC (ATP-Binding Cassette). Deux membres de cette famille ABC confèrent la propriété de résistance pléiotropique, P-gp (P-glycoprotein) et MRP1 (Multidrug Resistance-associated Protein). Nous avons mené une étude fonctionnelle sur l'activité de ces deux transporteurs dans la muqueuse olfactive à la fois chez le rat et la souris. Nous avons employé le test fluorométrique à la calcéine-AM sur des tranches coronales de la muqueuse olfactive incubées en présence d'inhibiteurs spécifiques des transporteurs de la résistance pléiotropique, vérapamil et cyclosporine A comme inhibiteurs de Pgp ainsi que probénécide et MK571 comme inhibiteurs de MRP1. Chacun de ces quatre inhibiteurs provoque une augmentation significative de l'intensité de la fluorescence.Afin de savoir si les transporteurs de la résistance pléiotropique peuvent être impliqués dans la réponse olfactive nous avons examiné les réponses évoquées par des odorants seuls ou mélangés à l'aide d'enregistrements d'électro-olfactogrammes (EOG). En présence des deux inhibiteurs de MRP1, l'amplitude maximale des EOG est significativement réduite pour chaque stimulus odorant testé, tandis que les inhibiteurs de Pgp n'ont qu'un effet modéré ou nul. L'expression des gènes codant pour Pgp et MRP1 dans l'épithélium olfactif ont ensuite été confirmées par RT-PCR. L'ensemble de ces résultats suggère que les transporteurs MRP1 et Pgp sont présents et fonctionnels dans l'épithélium olfactif principal des rongeurs et sont impliqués dans la réponse aux odorants. Leur fonction précise dans l'olfaction reste à élucider
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Nguyen, Duc Trung. "L'olfaction dans la polypose nasosinusienne avec et sans l'hamartome épithéliale respiratoire adématoïde de la fente olfactive." Thesis, Université de Lorraine, 2012. http://www.theses.fr/2012LORR0233/document.
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Contexte : Le pronostic de la fonction olfactive après chirurgie de la fente olfactive (FO) dans la polypose nasosinusienne (PNS) n'est pas connu. Objectifs : 1) Préciser la localisation des polypes dans les différents sous-compartiments de l'ethmoïde ; 2) Déterminer la corrélation entre l'auto-évaluation de l'odorat et les résultats de Sniffin'Sticks test ainsi qu'entre l'auto-évaluation de l'odorat et de l'obstruction nasale chez les patients porteurs d'une PNS avec ou sans hamartome épithélial respiratoire adénomatoïde des fentes olfactives (HERA - FO); 3) Évaluer la fonction olfactive avant et 6 semaines après chirurgie de la PNS comportant une chirurgie de la FO et rechercher les facteurs pronostiques de la récupération de l'olfaction après chirurgie. Échantillons : Ce travail repose sur des études observationnelles rétrospectives et prospectives chez les patients atteints de PNS opérés par voie endoscopique selon la procédure de nasalisation de Septembre 2009 à Novembre 2010 dans le service ORL du CHU de Nancy. Résultats : 1) Dans la PNS, les polypes se développaient dans tous les compartiments ethmoïdaux (au niveau du méat moyen dans 98%, de la fente olfactive postérieure dans 75%, du méat supérieur dans 61%, du cornet moyen dans 50% et de la FO antérieure dans 40% des cas); 2) Il existait une forte corrélation entre l'auto-évaluation et la mesure de l'olfaction avant la chirurgie (r =-0,66 ; p<0,0001) et après la chirurgie (r =-0,67 a 6 semaines r = -0.66 a 7 mois, p<0,0001). La corrélation était plus faible avant chirurgie (r =-0,35; p=0,01) qu'après chirurgie chez les patients hypo-anosmiques (r =-0,74 ; p<0,0001 a 6 semaines et r =-0,73 ; p=0,0002 a 7 mois). Les auto-évaluations de l'obstruction nasale et des troubles de l'odorat n'étaient pas corrélées lorsque les deux symptômes étaient dissocies ; 3) Il existait une relation étroite entre la présence de l'HERA dans les FO et l'ancienneté de la PNS (p= 0,0009), l'asthme (p = 0,004) et les antécédents de la chirurgie de PNS (p = 0,0006). Les facteurs prédictifs de non-récupération de la fonction olfactive après la chirurgie étaient un bas score TI préopératoire (p = 0,028), l'antécédent de résection des cornets moyens au cours des procédures chirurgicales précédentes (p = 0,0018), et la résection récente des cornets moyens (p = 0,04). L'histologie des polypes (HERA vs Polype éosinophile) et le type de geste sur les FO (biopsies vs exérèse des polypes) n'étaient pas des facteurs prédictifs pour la non-récupération de l'odorat. Conclusion : l'évaluation de l'odorat dans la PNS est complexe et nécessite une combinaison de tests psychophysiques et d'auto-évaluation. La chirurgie de la fente olfactive dans la PNS n'est pas un facteur péjoratif du pronostic olfactif en post-opératoireBackground: The olfactory outcome after surgery of the olfactory clefts (OC) in patients with nasal polyposis (NP) is unknown. Objectifs: 1) to refine the description of the polyps' origin within the different subcompartments of the ethmoidal bone; 2) to investigate correlations, before and after surgery, between the sense of smell self-ratings and measures of olfactory function, and self-ratings of sense of smell and nasal obstruction; 3) to assess the olfactory outcome after surgery of ethmoidal labyrinths and OC for either Eosinophilic Polyps (EP) or Respiratory Epithelial Adenomatoid Hamartoma (REAH) in patients with nasal polyposis (NP). Samples: All patients with NP operated according to the nasalization procedure from September 2009 to November 2010 in our tertiary hospital (CHU de Nancy) were enrolled in these retrospective and prospective studies. Results: 1) Polyps were found in the middle meatus (98%), in the posterior olfactory fossa (75%), in the superior meatus (61%), on the middle turbinate proper (50%) and in the anterior olfactory fossa (40%); 2) Overall, self-ratings and measures of olfactory function correlated strongly preoperatively (r = - 0.66, p < 0.0001) and postoperatively (r = -0.67 at 6 weeks and -0.66 at 7 months, p < 0.0001). This relationship was better in patients with previous surgery. The correlation was weaker before (r = -0.35, p=0.01) than after surgery in hyposmic/anosmic patients (r = -0.74, p < 0.0001 at 6 weeks and r = -0.73, p = 0.0002 at 7 months) and wasn't found in normosmic patients. Self-ratings of nasal patency and smell were not correlated when the two complaints were dissociated; 3) There was a close relationship between the presence of REAH-OC and the duration of NP disease (p=.0009), asthma (p=.004) and previous surgery (p=.0006). Predictors of poor olfactory outcomes after surgery were low TI score before surgery (p = 0.028), history of previous middle turbinate resection (p = 0.0018), and recent middle turbinate resection (p = 0.04). Polyp histology and surgery of the OC were not predictors of poor olfactory outcomes. Conclusion: The evaluation of the sense of smell in patients with NP should be performed in combination of psychophysic tests and self-ratings of the olfactory function. The resection of REAH or EP of the OC in patients with NP does not worsen but instead can improve the postoperative olfaction
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Gliem, Sebastian. "Characterization of olfactory receptor gene expression in the olfactory epithelium of larval Xenopus laevis." Doctoral thesis, 2010. http://hdl.handle.net/11858/00-1735-0000-0006-B5B9-D.
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Schmachtenberg, Oliver [Verfasser]. "Nitric oxide in the olfactory epithelium / von Oliver Schmachtenberg." 2001. http://d-nb.info/962820598/34.
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Lee, Ting-Hein, and 李亭輝. "The expression of neuronal intermediate filament proteins in the developing mouse olfactory epithelium and olfactory bulb." Thesis, 1998. http://ndltd.ncl.edu.tw/handle/90410238719307512234.
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Brozzetti, Lorenzo. "Neurodegeneration associated-proteins in human olfactory epithelium: immunocytochemical and biomolecular study in healthy subjects and patients with synucleinopathies." Doctoral thesis, 2020. http://hdl.handle.net/11562/1017250.
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Olfactory impairment is considered an initial disturbance of several neurodegenerative diseases (NDs), including Parkinson’s disease (PD) and Alzheimer’s disease (AD). In addition, smell impairment precedes a decade, or even longer, the onset of motor or cognitive symptoms. Olfactory signals are detected by olfactory receptor proteins (ORPs) expressed in the cilia of olfactory receptor neurons (ONs). ONs are the distinctive cellular components of the peripheral olfactory epithelium (OE) and lie in the nasal vault. ONs axons pass the cribriform plate and reach the olfactory bulb (OB) where the olfactory stimuli are processed and sent to the superior nuclei of the CNS. Previous studies in AD and other neurodegenerative disorders have shown the presence of β-amyloid deposits in the OB, neurofibrillary tangles, as well as Lewy body pathology. OB represents the brain area earlier involved in the neuropathological process, decades before the development of clinical symptoms. Therefore, OB can be considered a target in the study of neurodegenerative diseases in their early molecular processes. Moreover, the OB of healthy subjects presents deposits of aggregated proteins confirming that these aggregates are deposited in a prodromal disease stage. Since the OB is an early accumulation site of aggregated proteins and the synapses derive from the ONs, it is possible that the first event of protein aggregation occurs in OE. ONs are directly exposed to the external environment including chemical/physical toxic injuries and such micro-environment predisposes to abnormal protein processing and folding (Sammeta and McClintock 2010). In addition, ONs and all other mature cell components have a half-life of three months and programmed apoptosis. The neural activity is maintained by a constant cellular turn-over, which is sustained by the basal stem cells. This regeneration process is persistent during the whole life of an individual, albeit with a decreasing rate with aging. Extensive scientific literature indicates the neuronal damage as the consequence of exposure to toxic injuries leading to neurodegeneration and ONs are a natural model of this noxious process (Lema Tomé, Tyson et al. 2013). The hypothesis of this pathological pathway is supported by several studies, in which aggregated forms of α-synuclein, tau and β-amyloid are detected in olfactory mucosa (OM) biopsies as well as in autoptic samples of patients with Parkinson’s disease (PD), Lewy body dementia (LBD), Frontotemporal dementia (FTD) and Alzheimer disease (AD) (Funabe, Takao et al. 2013) (Saito, Shioya et al. 2016) (Tabaton, Cammarata et al. 1991) (Talamo, Rudel et al. 1989) (Crino, Greenberg et al. 1995) (Arnold, Lee et al. 2010). In this study, we investigated for the first-time primary ONs sampled ex vivo using olfactory brushing (OBg) in normal subjects and patients with different neurodegenerative disorders. Because of its convenient location, OE is easily accessible and can be sampled to obtain the ONs in the tissue outer layer. This sampling method is harmless and non-invasive, bypassing potential artifacts due to post mortem specimens as well as avoiding the invasiveness of biopsy procedures. Recently, we showed that OBg procedure in Creutzfeldt-Jakob Disease (CJD) patients allows efficient OM sampling for the Real-Time Quaking-Induced Conversion (RT-QuIC) assay. We specifically amplified pathological prion protein (PrPSc) providing a diagnostic intra vitam test with sensitivity and specificity nearly to 100% (Orrú, Bongianni et al. 2014). For the purpose of our study, we firstly defined the phenotypic characterization of the human olfactory cells sampled with OBg from healthy subjects. Distinct antibodies were selected to analyze the olfactory epithelium cells: olfactory marker protein (OMP), neuron-specific class III β-tubulin (TUJ-1), protein gene product 9.5 (PGP 9.5), Pan-Cytokeratin (PCK). Secondly, we aimed to determine the expression patterns of the major misfolded proteins involved in the main neurodegenerative diseases. In particular, the selected proteins were: α-synuclein, APP/beta-amyloid, tau, and TDP-43. The identification of the expression patterns of these proteins in the ONs might provide information to understand the abnormal molecular mechanisms in the initial misfolding species involved in the pathological process. Moreover, in this study, we speculated on the subcellular locale where the protein aggregation may occur. Furthermore, by demonstrating the constitutive expression of the native NDs-associated proteins in the OE, we could assume that they may represent a potential template for triggering the aggregation process. Based on the immunocytochemistry analysis, we investigated the α-synuclein expression in patients affected by different synucleinopathies. In fact, α-synuclein misfolding and aggregation mechanisms are involved in the pathogenesis of neurodegenerative disorders such as Parkinson's disease (PD), dementia with Lewy bodies (LBD) and multiple system atrophy (MSA), which are all characterized by α-synuclein fibrils deposition (Spillantini, Schmidt et al. 1997). Finally, we analyzed the immunocytochemistry results in OM samples tested by α-synuclein RT-QuIC (α-syn RT-QuIC).
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Liang, Kai-Hao, and 梁凱豪. "Characterization of the DNA elements that regulate the expression of CYP11A1 promoter in mouse olfactory epithelium." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/65057000411803513176.
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碩士國立臺灣大學
生理學研究所
101
Abstract Steroid hormones are mainly synthesized in adrenal cortex, gonads and placenta. Recent studies indicate that they are also produced in CNS. These so-called neurosteroids do affect physiological functions including neural survival, myelination, neurogenesis, etc. CYP11A1 encodes P450scc (cytochrome P450 side chain cleavage), which catalyzes the first and the rate-limiting step during steroidogenesis that changes cholesterol into pregnenolone. Thus, CYP11A1 plays an important part in steroidogenesis. CYP11A1 can be expressed in steroidogenic tissue, but at low level in brain. This makes CYP11A1 difficult to be detected and studied in brain. We tried to investigate the regulation and distribution of CYP11A1 by transgenic mice and proved that 4.4 kb length of CYP11A1 promoter is able to promote Cre recombinase expression in brain. Furthermore, we have curtailed the range which may contain the potential DNA elements in CYP11A1 promoter. In this thesis, we spliced the potential regulatory sequence into short segments and incubated them with mouse olfactory epithelium nuclear extracts for electrophoretic mobility shift assay (EMSA). Our results indicate that the binding sequences of olfactory epithelium nuclear molecules do exist in CYP11A1 promoter and may play important roles in its neural regulation. Since using transgenic mice for promoter research costs time and money, we are looking for some other in vitro transgenic system. Therefore, we constructed the retina electroporation system. We sent CYP11A1 promoter with Cre recombinase as the reporter gene in to retina tissue dissociated from mice cub. The results showed that although the retina electroporation system is able to transfect plasmids in to retina tissue, it still cannot help the weak promoter to trigger the reporter gene expression. In summary, this system is suitable for promoter studies except CYP11A1 promoter.
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Jou, Yuan-Jia, and 周原加. "Effects of Neuregulin-1 Gene Mutation on the Structure and Neurogenesis of the Olfactory Epithelium in Adult Mice." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/67634559478064973745.
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碩士國立臺灣大學
解剖學暨生物細胞學研究所
100
Olfactory system is closely associatied with emotion and memory. Olfactory malfunction may lead to abnormal emotion, and this may play roles in mood-related disease, such as schizophrenia. Previous studies indicate that abnormal olfactory functions are common symptoms of schizophrenics, which include disturbed identification, discrimination, memory, and detection of odors. As shown by MRI scans, reduced bulb volumes were seen in schizophrenic patients. Neuregulin 1 (NRG1) is thought to be one of the susceptibility genes of schizophrenia. Neuregulin 1 (NRG1) and its receptors, ErbBs, may play important roles in the development of nervous system. Thus, the goal of this experiment was to examine the effects of the mutation of NRG1 gene on the olfaction and olfactory epithelium (OE) neurogenesis. Following behavioral observation 8 week-old wildtype (WT, NRG1+/+) and mutant (Mut, NRG1+/-) mice were intraperitoneally injected with bromodeoxyuridine (BrdU), 150 mg/kg, once daily for 3 consecutive days. On the 4th day (BrdU-D4), 10th day (BrdU-D10), 21st day (BrdU-D21) and 28th day (BrdU-D28) the mice were subjected to preparation for immunocytochemistry on their OE. Our results are as follows. 1. Behavior test results: NRG1 mutant mice showed decreased average body weight by about 9.2%. As revealed from the open field test, the distance and duration traveled by mutant mice were similar in the central and peripheral parts of the field respectively to that of WT. The olfactory habituation/dishabituation test revealed that, mutant mice were unable to discriminate different odors and litter odors. 2. Morphological results: (A) In the dorsal region of OE (i) The numbers of BrdU-positive cells were increased by 94.6% and 65.8% in the BrdU-D4 and BrdU-D10 mutant mice, compared to WT, whereas BrdU-D21 and BrdU-D28 mutant mice were similar to WT. (ii) Mutant mice contained 45.6% less number of the doublecortin (DCX) , a marker for neuroblasts, positive cells than that of WT. (iii) The levels of the olfactory marker protein (OMP) for mature olfactory receptor neurons (ORNs) were decreased by 28.9% and 18.6% in its expression area and OD in the Mutant mice. (iv) OE of mutant mice had 37.6% lower number of calretinin (CR) positive cells. (v) Mutant mice had 75.8% more number of cleaved caspase 3 positive cells. (B) In the septal region of OE (i) The numbers of BrdU-positive cells were increased by 62.1%, 54.5% and 54.6% in the BrdU-D4, BrdU-D10 and BrdU-D28 mutant mice, compared to WT, whereas BrdU-D21 mutant mice were similar to WT. (ii) Mutant mice contained 31.5% less number of the doublecortin (DCX) positive cells than that of WT. (iii) Mutant mice had 38.5% more number of cleaved caspase 3 positive cells, whereas OMP and CR expression were similar to WT. (C) Electron microscopy revealed that compared to that of WT, the number of nuclear membrane pores seemed incereased in the mutant basal cell and a single cilium arose from its basal part in the mutant ORN, instead of the multiple cilia arising from one single basal part in WT ORNs. Our results also confirmed the presence of NRG1 and ErbB 2 receptor in OE. These point out that the abnormal NRG1 protein may bind to the ErbB 2, leading to altered intracellular signaling of those specific cells. In the mutant mice, the decreased number and abnormal ultrastructure of olfactory receptor neurons may be related to their abnormal behavior and increased neurogenesis and apoptosis. NRG1 gene activity apparently is critically involved in the proliferation, differentiation and survival of neural cells, and thus may play important roles in the pathogenesis of schizophrenia.
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Manzini, Ivan [Verfasser]. "Diversity of transduction mechanisms in receptor neurons of the main olfactory epithelium in Xenopus laevis tadpoles / submitted by Ivan Manzini." 2003. http://d-nb.info/975110926/34.
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Adler, Jenny [Verfasser]. "Charakterisierung des Plasmamembranproteoms aus dem olfaktorischen Epithel von Mus musculus = Characterization of the plasma membrane proteome of the olfactory epithelium from Mus musculus / vorgelegt von Jenny Adler." 2008. http://d-nb.info/993947727/34.
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Kurtanska, Silvia. "Pharmakologische Charakterisierung der purinergen Rezeptoren der Stützellen der olfaktorischen Mukosa des larvalen Xenopus laevis." Doctoral thesis, 2011. http://hdl.handle.net/11858/00-1735-0000-0006-B1CE-1.
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Extrazelulläre Purine und Pyrimidine sind wichtige Signalmoleküle, die über membranständige Rezeptoren, so genannte purinerge Rezeptoren ihre biologischen Effekte vermitteln. In der vorliegenden Arbeit wurden ATP-induzierte Antworten in den Stützzellen des olfaktorischen Epithels mit Hilfe der Calcium-Imaging-Technik charakterisiert.Die Applikation von ATP induzierte Zunahmen der intrazellulären Kalziumkonzentration ([Ca2+]i) sowohl in Anwesenheit, als auch in Abwesenheit von extrazellulärem Kalzium. Anders bei Anwendung von CPA, einem spezifischen Hemmstoff der Ca2+-ATPase des sarkoplasmatischen bzw. endoplasmatischen Retikulums. In diesen Versuchen wurden die ATP-induzierten [Ca2+]i-Zunahmen komplett aufgehoben. Das zeigt, dass die ATP-induzierten [Ca2+]i-Zunahmen in Stützzellen größtenteils, wenn nicht vollständig, durch die Aktivierung von G-Protein gekoppelten P2Y-Rezeptoren ausgelöst werden. Die ermittelte Wirkpotenz purinerger Agonisten war UTP>ATP>ATPγS. Die ATP-induzierten [Ca2+]i-Zunahmen konnten durch die purinergen Antagonisten PPADS und RB2 reduziert werden. Die hemmende Wirkung des purinergen Antagonisten Suramin blieb aus. Zusammen weisen die oben genannten Ergebnisse dieser Arbeit darauf hin, dass extrazelluläre Nukleotide die Stützzellen des olfaktorischen Epithels über P2Y2 / P2Y4-artige Rezeptoren aktivieren. Zusätzlich zeigten die Versuche mit dem Ektonukleotidase-Hemmstoff ARL 67156, dass im olfaktorischen Epithel von larvalen Xenopus laevis eine hohe Ektonukleotidasenaktivität herrscht.
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Šmít, Daniel. "Analýza dynamických interakcí těl axonů a jejich biofyzikální modelování." Doctoral thesis, 2017. http://www.nusl.cz/ntk/nusl-354435.
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in English While axon fasciculation plays a key role in the development of neural networks, very lit- tle is known about its dynamics and the underlying biophysical mechanisms. In a model system composed of neurons grown ex vivo from explants of embryonic mouse olfactory epithelia, we observed that axons dynamically interact with each other through their shafts, leading to zippering and unzippering behaviour that regulates their fasciculation. Taking advantage of this new preparation suitable for studying such interactions, we carried out a detailed biophysical analysis of zippering, occurring either spontaneously or induced by micromanipulations and pharmacological treatments. We show that zippering arises from the competition of axon-axon adhesion and me- chanical tension in the axons. This is upheld on quantitative level by conforming change of network global structure in response to various pharmacological treatments, without active involvement of growth cones. The calibrated manipulations of interacting shafts provide qualitative support for the hypothesis, and also allow us to quantify the mechan- ical tension of axons in our system. Furthermore, we introduce a biophysical model of the zippering dynamics, which efficiently serves the purpose of estimating the magnitude of remaining involved...
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Carter, Lindsay A. "Olfactory epithelial horizonal basal cells : an assessment of stem cell candidacy and behavioural regulation in vivo and in vitro." Thesis, 2002. http://hdl.handle.net/2429/12405.
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In the olfactory epithelium (OE), new olfactory receptor neurons (ORNS) are
continually generated throughout mammalian adulthood. Given this substantial neuronal
turnover, a stem cell is proposed to reside within the basal compartment of the OE, which
generates ORNs on demand when stimulated by changes in its microenvironment.
Although previous studies have identified possible candidates for the olfactory stem cell,
its exact identity is as yet unknown. We hypothesize that a population o f horizontal basal
cells (HBCs), situated upon the basement membrane of the OE, contains stem cells that
contribute to olfactory neurogenesis.
A major impediment to the study of these cells is the lack of reliable cell surface
molecular markers to distinguish them from other OE cell types. By screening a panel of
selected clusters of differentiation (CD) antigens, we have identified three new cell
surface markers for the HBC population, namely intercellular adhesion molecule -1
(ICAM-1), β₁ integrin and β₄ integrin. Using these markers to characterize the HBC
layer following bulbectomy-induced ORN loss, we have provided evidence of stem cell
traits in vivo, including proliferative quiescence relative to OE progenitors, response to
lesion, and possible molecular heterogeneity within the HBC compartment. In addition,
these studies indicate changes in the populational and subcellular distribution of HBC
markers upon loss of ORNs, suggesting a role for these adhesion receptors in the
regulation of HBC function in addition to highlighting possible molecular similarities to
stem cells of other self-renewing tissues. We have developed a method to select for
HBCs in vitro using magnetic activated cell sorting (MACS) and by exploiting their
expression of ICAM-1. Using in vitro colony-forming analyses, we obtained evidence
that the ICAM-1+ population is enriched for progenitor activity. Further, the efficiency
of colony formation can be modulated in vitro by growth factors and adhesive substrates.
Lastly, immunohistochemical analysis demonstrated that globose basal cell (GBC)
progenitors, ORNs and olfactory ensheathing glia (OEGs) are generated by the ICAM-1+
fraction in clonal culture. Based on these results, we conclude that ICAM-1+ HBCs
contribute to the progenitor cell compartment, possibly as stem cells, during olfactory
neurogenesis and that the function of these cells may be modulated via adhesion and
growth factor signaling by components resident within their in vivo microenvironment.