Dissertations / Theses: 'Glial cells'

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Förster, Bettina Ulrike. "Talin in glial cells." Thesis, University of Cambridge, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612772.

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Nazareth, Lynn. "Determining Cellular and Molecular Mechanisms Behind Glial Cell Phagocytosis." Thesis, Griffith University, 2021. http://hdl.handle.net/10072/408099.

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Phagocytosis (“cell eating”) is an immunobiological process required for maintenance of systemic homoeostasis under normal physiological conditions (during development and adulthood) and in various pathologies. Phagocytosis is a receptor-mediated event, wherein a phagocytic cell recognizes, engulfs and degrades specific targets that need to be eliminated. The targets can be either “self-targets”, such as dead or damaged cells, or “non-self-targets”, such as microorganisms. In the nervous system, the “first responding” phagocytes are usually the supporting glial cells. Based on the location they are present in, glial cells are classified as either CNS or PNS glia. The key phagocytic glia in the CNS are astrocytes and microglia, and in the PNS, Schwann cells (SCs). Some peripheral nerves, however, have other glial types which mediate this function, such as olfactory ensheathing cells (OECs) in the olfactory nerve. Efficient phagocytosis is essential for regeneration after nervous system injury, but after CNS injury, glial phagocytosis is often inefficient. In contrast, after PNS injury, glia rapidly phagocytose and clear the cellular and myelin debris resulting from the injury. Due to their ability to support nerve growth, particularly via physical support and secretion of growth/guidance factors, while simultaneously performing phagocytosis; transplantation of SCs and OECs have promising potential to treat CNS injuries. However, phagocytosis is a highly specialized function and the key molecular and cellular components in PNS glial phagocytosis are largely unknown. If these could be characterized, new drug targets may be revealed that can further promote glial-mediated neural regeneration (but without causing an excessive inflammatory response). The site of a CNS injury is a complex environment, with cell death occurring via different mechanisms. These include distinct types of necrosis and apoptosis, and glia may respond differently to these distinct “self-targets”. Hence, in this Thesis, I investigated key cellular and molecular mechanisms involved in OEC- and SC-mediated phagocytosis of cells undergoing various forms of death. I discovered that OECs and SCs are indeed competent phagocytes that can recognize, internalize and degrade a range of “self-targets”. Both cell types expressed a number of phagocytic receptors, including phosphatidylserine (PS) recognition receptors, pathogen recognition receptors (PRRs), scavenger receptors, Fcγ receptors (FcγRs) and complement receptors (CRs). OECs and SCs both rapidly recognised and engulfed various cellular targets (within 2 h). Recognition of targets occurred mainly via PS displayed on the dying cell surface, with potential involvement of PRRs. The family of small Rho GTPases (Rac, Cdc42 and Rho) were also important for target engulfment. However, while engulfment was rapid, breakdown was relatively slow, particularly when the targets were necrotic bodies and myelin debris (especially when compared to professional phagocytes, i.e., macrophages). Engulfment of apoptotic targets resulted in anti-inflammatory cytokine production, however, necrotic target uptake led to a proinflammatory response. Overall, OECs phagocytosed larger amounts of targets over time, as well as processed targets faster, than SCs. During the process of phagocytosis, OECs also produced less pro-inflammatory, but more immunomodulatory, factors than SCs. Thus, OECs were more efficient in phagocytosing “self-targets” than SCs, accompanied by a more favourable immune response, suggesting that OECs may be better transplantation candidates than SCs. Two peripheral nerves, the olfactory nerve and the trigeminal nerve (intranasal branches) extend between the nasal cavity and the brain. These nerves are populated by OECs and SCs, respectively. These nerves have been shown to function as a pathway by which certain microbes can enter the brain, leading to CNS infection. The nasal mucosa, and associated nasal-associated lymphoid tissue (NALT) constitute a strong physical and immunological barrier against microorganisms, and those that do manage to penetrate the mucosa are considered to be phagocytosed by OECs and SCs in the nerves. However, microbes that can infect the CNS via these two peripheral nerves have been shown to evade phagocytic destruction and instead infect PNS glia. In this Thesis, I also investigated how OECs and SCs respond to bacterium thought to infect the CNS via nerves - Chlamydia muridarum. I chose this bacterium as it is commonly used to model C. pneumoniae infections in mice. C. pneumoniae CNS infection has been suggested to contribute to the development of late-onset dementia, thus being clinically relevant. I found that C. muridarum, which replicates in intracellular inclusion bodies, infected both OECs and SCs, however, the glia were not as susceptible to infection and intracellular bacterial growth as non-immune cells. Both OECs and SCs mounted a significant immune response to bacterial challenge, with OECs producing the strongest response. Despite this, C. muridarum could manipulate various intracellular and phagocytic machinery pathways to survive inside the glia, including pathways involving small Rho GTPases (Rac, Cdc42 and Rho) and PI3K/Akt. C. muridarum also suppressed lysosomal recruitment by “hijacking” Ras-like small GTPases (Rabs) responsible for intracellular trafficking and host nutrient scavenging. Thus, C. muridarum could escape phagocytosis (degradation) and grow inside glia. This is potentially a key reason by which the bacteria may disseminate through peripheral nerves, leading to CNS infection. The findings presented in this Thesis (including resultant publications), increases our understanding of how PNS glia remove dying and damaged “self”, including key cellular and molecular mechanisms involved in OEC and SC-mediated phagocytosis. The current study also, by characterizing how the glia responded to C. muridarum, explored the crucial dichotomy between phagocytosis vs infection. Internalization of bacteria into a cell can lead to either or both. In the case of OECs and SCs, C. muridarum challenge led to infection but also an immune response, restricted bacterial growth and likely also killing of a proportion of bacteria. This understanding may provide us with tools/drug targets for manipulation of various aspects of the PNS glia-mediated phagocytic processes. This could involve improved clearance of cellular debris without adverse inflammatory events post-transplantation into a nervous system injury site. Tweaking certain aspects of the phagocytic pathway may also prevent infections by microbes that can use the nose-to-brain pathway to infect the CNS, without using antibiotics (thus, not contributing to antimicrobial resistance). Finally, this thesis has also given us some interesting insights into differences between the two types of PNS glia. OECs and SCs, were considered to be quite similar in the past and both are deemed as good transplantation candidates. Overall, OECs were found to be more efficient phagocytes and equipped with additional molecular components of phagocytic pathways than SCs. OECs also produced a more favourable immune response than SCs in response to damaged “self”. In contrast, OECs mounted a stronger bactericidal immune response to C. muridarum than SCs, suggesting that OECs exhibit better antimicrobial protection mechanisms than SCs.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Pharmacy & Med Sci
Griffith Health
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Schuliga, Michael, and michael schuliga@deakin edu au. "Steroidogenesis in cultured mammalian glial cells." Deakin University. School of Biological and Chemical Sciences, 1998. http://tux.lib.deakin.edu.au./adt-VDU/public/adt-VDU20061207.154152.

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A protocol for culturing mammalian type 1 astrocytic cells, using female post-natal rat cerebral cortical tissue, was established and refined for use in steroidogenic metabolic studies incorporating progestin radioisotopes. Cultures were characterised for homogeneity using standard morphological and immunostaining techniques. Qualitative and quantitative studies were conducted to characterise the progesterone (P) metabolic pathways present in astrocytes in vitro. Of particular interest was the formation of the P metabolite, 5á-pregnan-3á-ol-20-one (THP). THP is a GABA(A) receptor agonist, believed to play a vital role in neural functioning and CNS homeostasis. One aim of this study was to observe any modulatory effects selected neuroactive ligands have on the conversion of P into THP, in an attempt to link astrocytic steroidogenesis with neuronal control. In qualitative studies, chromatographic procedures were used to establish the progestin profile of cerebral cortical astrocytes. Tritiated P, DHP (5á-pregnan-3,20-dione) and THP incurbates were preliminary fractionated by either normal phase (NP) or reverse phase (RP) high performance liquid chromatography (HPLC). The radiometabolites associated with each fraction were further chromatographed, before and/or after chemical derivatistation, by the aforemention HPLC procedures and thin layer chromatography (TLC). Steroid radiometabolites were tentatively identified by comparing their chromatographic mobility with authentic steroids. The identity of the main putative 5á-reduced P metabolities, DHP, THP and 5á-pregnan-3á,20á-diol (20áOH-THP) were further confirmed by isotopic dilution analysis. Their conclusive identification, along with the tentative identification of 20á-hydroxypreg-4-en-3-one (20áOH-P) and 20á-hydroxy-5á-pregnan-3-one (20áOH-DHP), verify the localisation of 5á-reductase, 3á-hydroxy steroif oxidoreductase (HSOR), and 20á-HSOR activity in the cultured astrocytes utilised in this study programme. Other minor metabolites detected were tentatively identified, including 5á-pregnan-3á,21-diol-20-one (THDoc), indicating the presence of 21-hydroxylase enzymatic activity. THDoc, like THP, is a GABA(A) receptor agonist. The chemical and physical characterisation of several yet unidentified progestin metabolites, associated with a highly polar RP HPLC fraction (designated RP peak 1*), indicate the presence of one or more extra hydroxylase enzymes. Quantitative analysis included a preliminary study. In this study, the percentage yields of radiometabolites formed in cultures incubated with increasing substrate concentrations of (3)H-P for 24 hours were determined. At the lower concentrations examined (ie 0.5 to 50nM), the metabolites associated with the polar RP HPLC fraction (RP peak 1*) collectively have the highest percentage yield. They are subsequently considered metabolic end products of degradative catabolic P pathways. The percentage yield of THP peaks in the medium concentration ranges (ie 5 to 500nM), whereas DHP remains fairly static at a low level with increasing concentration. Both DHP and THP are considered metabolic pathway intermediates. The percentage yield of 20áOH-THP continues to increase with increasing concentration over 5nM, superseding THP approaching the highest concentration examined (5000nM). This indicated the formation of 20áOH-THP does not occur entirely via THP. 20áOH-THP also possibly serves as the direct intermediate in the formation of the main radiometabolites associated with RP peak 1*. A time/yield study incorporating incubation times from one to 24 hours was also conducted. The full array of radiometabolites (individually or in groups) formed in astrocyte cultures incubated with 50nM tritiated P, DHP of THP, were assayed. Cultures were observed to rapidly convert any DHP into THP, showing astrocytic 3á-HSOR activity is very high. The study also showed 5á-reduction (ie the conversation of P into DHP) is the rate limiting reaction in the two step conversion of P into THP. 5á-Reduction also appears to be a rate limiting step in the formation of 20á-hydroxylated metabolites in astrocytes. Cultures incubated with the tritiated 5á-reduced pregnanes from one to four hours form greater quantities to 20á-hydroxylated radiometabolites compared to cultures incubated with (3)H-P. The time yield/studies also provided further evidence the unidentified polar radiometabolites associated with RP peak 1* are metabolic end products. For the P and DHP incubates, the collective formation of the aforementioned polar radiometabolites initially lags behind the formation of THP. As the formation of the latter begins to plateau with increasing time between four to 24 hours, the net yield of radiometabolites associated with RP peak 1* continues to rise. The time/yield studies also indicate 5á-reduction and perhaps 3á-hydroxylation are pre-requisite steps in the formation of the polar metabolites. Cultures incubated with the 5á-reduced progestins from one to four hours form higher yields of the radiometabolites associated with RP peak 1* compared to cultures incubated with P as substrate. The net yields of the radiometabolites associated with RP peak 1* for cultures incubated with THP were substantially higher compared to cultures incubated with DHP after equivalent times. The effect selected neuroligands have on the yield of radiometabolites formed by cultured astrocytes incubated with 50nM (3)H-P was also examined. Dibutyryl cyclic adenosine monophosphate (DBcAMP), not actually a neuroligand per se, but an analog of the intracellular secondary messenger cAMP, was also utilised in these studies. The inhibitory neurotransmitter ã-amino-nbutyric acid (GABA), DBcAMP and isoproterenol (a â-adrenergic receptor agonist) all quickly induce a transient but substantial increase in 20á-HSOR activity in cultured astrocytes. Cultures pretreated with these three compounds (10, 20 and 1µM respectively) form substantially higher yields of 20á-hydroxylated metabolites, including 20áOH-THP (between 200 to 580% greater), when incubated with 50nM (3)H-P for one to four hours. These increases also coincide with increases in the net yield of metabolites formed (by 16 to 48%). The same pre-treated cultures form significantly lower yields of THP, by 25 to 41%, after one hour. This is most likely due to the increased metabolism of any formed THP into 20áOH-THP. Octopamine (an á-adrenergic agonist) only induces a slight increase in 20á-HSOR activity, having relatively little effect on the yield of 20áOH-THP formed. Pretreatment with octopamine induces a significant increase in the yield of THP for cultures incubated with (3)H-P for four hours (by 24%). The increase in THP formation appears to be due to an increase in 3á-HSOR activity, as judged by the concomitant drop in the yield of the 5á-reduced, 3-keto substrates. An increase in 5á-reductase activity cannot be excluded however. Isoproterenol appears to induce an increase in 5á-reductase activity as isoproterenol appears to induce an increase in 5á-reductase activity as isoproterenol one and four hour incubates have higher yields of DHP. This is in contrast to the other three incubates. After 12 hours, all incubates have higher yields of THP (15-30%).

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Mellor, Robert. "Neurochemical studies on cultured glial cells." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300038.

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Stuckey, Crystal Elaine. "Oxidative Stress and Cell Death in Osmotically Swollen Glial Cells." Wright State University / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=wright1208492663.

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Rabah, Yasmine. "Satellite glial cell-proprioceptor interactions in dorsal root ganglia Characterization of transgenic mouse lines for selectively targeting glial cells in dorsal root ganglia Satellite glial cells modulate proprioceptive neuron function." Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCB208.

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Les neurones propriocepteurs sont nécessaires au contrôle du mouvement et à la locomotion. Ils connectent les fuseaux musculaires et les tendons aux motoneurones de la moelle épinière pour informer le système nerveux central de l’état d’élongation et de contraction des muscles. Leurs corps cellulaires sont localisés dans les ganglions rachidiens dorsaux (GRD), où ils sont intimement entourés de cellules gliales GFAP-positives appelées cellules satellites gliales (CSG). Comme les astrocytes du système nerveux central, les CSG expriment à leur surface des récepteurs couplés aux protéines Gq (Gq RCPG) qui peuvent être activés par les neurotransmetteurs libérés par les corps cellulaires de neurones sensoriels du GRD. Les corps cellulaires des neurones sensoriels expriment aussi un certain nombre de récepteurs et transmetteurs. Ces caractéristiques, ainsi que la proximité physique entre les CSG et les neurones sensoriels a permis d’émettre l’hypothèse que les deux types cellulaires sont capables de communiquer. De récentes données de la littérature suggèrent que les CSG et les neurones sensoriels responsables de la détection de la douleur sont capables de dialoguer. Cependant, à notre connaissance, aucune donnée n’a permis jusqu’à présent de démontrer une interaction entre les CSG et les neurones propriocepteurs. Dans cette étude, nous avons émis l’hypothèse que l’activation des Gq RCPG des CSG permet la modulation de l’activité des propriocepteurs. Pour tester cette hypothèse, nous avons utilisé des approches techniques complémentaires (imagerie calcique bi-photonique, immunohistochimie, biochimie et analyses comportementales) combinées à un outil chemogénétique puissant basé sur la technologie DREADD afin d’activer sélectivement la voie de signalisation Gq RCPG dans les CSG. Nous avons démontré dans une préparation de GRD intacte que les CSG sont capables de moduler l’activité des propriocepteurs via une signalisation purinergique. Pour tester la pertinence de cette communication, nous avons réalisé des expériences de comportement sensorimoteur et mis en évidence que l’activation des cellules gliales GFAP-positives induit des déficits sensorimoteurs. Déterminer si la modulation des propriocepteurs par les CSG affecte la transmission sensorimotrice a de profondes implications pour la compréhension du système sensorimoteur et de ses dérèglements
Proprioceptive neurons (one’s own neurons) are necessary for controlling motor control and locomotion. They arise from muscle spindles and tendons and synapse onto ventral horn motoneurons to deliver information about the length and contraction of muscles. Proprioceptor somata reside within the dorsal root ganglia (DRG) and are tightly enwrapped in a thin sheath of GFAP-expressing glial cells, called satellite glial cells (SGCs). Interestingly, SGCs express a number of Gq protein- coupled receptors (Gq GPCRs), which can be activated by neurotransmitters released by sensory neuron somata. Sensory neuron somata also express a number of receptors and transmitters. Both the expression of receptors and the close contact between SGCs and sensory neurons led to the hypothesis that these two cell types communicate. There is emerging evidence that SGCs and nociceptive sensory neuron (pain-sensing neurons) somata can communicate. Furthermore, to date, there is no study conducted on SGC-proprioceptor interaction. We hypothesized that SGC Gq GPCR signaling induces the release of neuroactive molecules from SGCs, leading to the modulation of proprioceptor activity. The main goal of this project has been to test this hypothesis using complementary technical approaches (2-photon Ca2+ imaging, immunohistochemistry, biochemistry and behavior) combined with a powerful chemogenetic DREADD-based tool to activate SGC Gq GPCR activity. We have demonstrated ex vivo that SGCs modulate proprioceptive neuron activity through a purinergic pathway. In order to test the physiological relevance of this discovery in vivo, we performed sensorimotor behavioral experiments and have shown that activating GFAP-expressing glial cells induces sensorimotor deficits. Determining whether SGC-induced proprioceptor activity has profound implications in the understanding of sensorimotor functions in health and diseases

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Nutt, Catherine L. "Mechanisms of drug resistance in glial cells." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq28512.pdf.

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Gao, Yuanqing. "Hypothalamic Glial Cells in Diet Induced Obesity." University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1447071648.

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Nieweg, Katja. "Cholesterol biosynthesis in neurons and glial cells." Université Louis Pasteur (Strasbourg) (1971-2008), 2007. https://publication-theses.unistra.fr/public/theses_doctorat/2007/NIEWEG_Katja_2007.pdf.

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Cette étude confirme l’hypothèse d’une dépendance des neurones en cholesterol astrocytaire au stade postnatal. Nos travaux montrent que les neurones ne peuvent assurer leurs besoins en cholestérol: L’accumulation de lanostérol et la lente conversion de stérols intermédiaires indiquent que les neurones produisent du cholesterol de façon moins efficace que les cellules gliales. La diminution le taux de cholestérol dans les neurones n’induit pas d’augmentation de l’expression des enzymes de sa voie de biosynthèse. L’absence de synthèse d’ester de cholesterol et d’organelles de stockage de cholesterol accentue la faible capacité des neurones à produire leur cholesterol. Enfin, l’apport en cholesterol par les cellules gliales induit l’arrêt de sa synthèse par les neurones. Cette étude démontre également que les neurones et astrocytes ont une composition distincte en stérol, qui pourrait être liée à des fonctions cellulaires spécifiques et impliquée lors de processus neurodégénératifs.

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Nieweg, Katja Pfrieger Frank. "Cholesterol biosynthesis in neurons and glial cells." Strasbourg : Université de Strasbourg, 2009. http://eprints-scd-ulp.u-strasbg.fr:8080/1048/01/NIEWEG_Katja_2007.pdf.

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KRISHNA, CHANDRAN ADWAID MANU. "MÜLLER GLIAL CELLS IN EPIRETINAL MEMBRANE FORMATION." Doctoral thesis, Università degli studi di Brescia, 2022. http://hdl.handle.net/11379/551759.

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Una membrana epiretinica (ERM) è un sottile strato di tessuto fibroso che può formarsi sulla superficie dell'area maculare della retina e causare problemi alla vista.Le cellule gliali di Müller sembrano svolgere un ruolo fondamentale nella patogenesi dell'ERM, dove varie citochine e fattori di crescita possono agire come modulatori autocrini e paracrini innescando la proliferazione, la migrazione, la transdifferenziazione e l'aumento dell'espressione dei marcatori della gliosi delle cellule di Müller. L'umor vitreo può rappresentare un serbatoio di mediatori patologici che si accumu Durante la prima parte del mio dottorato di ricerca ho partecipato a un progetto in cui abbiamo dimostrato che gli iERM rimossi chirurgicamente sono caratterizzati da un diverso pattern di espressione di geni associati a diverse popolazioni cellulari, matrice extracellulare e biomarcatori di citochine/fattori di crescita rilevanti per la patogenesi della malattia. Inoltre, il raggruppamento gerarchico dei dati di espressione genica ha identificato due cluster molecolari di membrane iERM associati a caratteristiche cliniche e SD-OCT distinte (denominate iERM-A e iERM-B). I pazienti iERM-A sono caratterizzati da manifestazioni cliniche meno gravi e un profilo di espressione genica iERM più "quiescente" rispetto ai pazienti iERM-B. Inoltre, mi sono concentrato sulla comprensione del ruolo delle cellule gliali di Müller nella patogenesi di iERM. Durante la progressione di iERM, le cellule gliali di Müller subiscono una transizione gliale-mesenchimale (GMT), un processo di transdifferenziazione caratterizzato dalla sottoregolazione dei marcatori delle cellule di Müller parallela alla sovraregolazione dei marcatori dei miofibroblasti pro-fibrotici. Il presente studio ha dimostrato che il fluido vitreo ottenuto dai pazienti iERM induce proliferazione, migrazione e GMT nelle cellule MIO-M1 Müller, un fenotipo coerente con il comportamento delle cellule Müller durante la progressione iERM. Tuttavia, anche se il fluido vitreo ottenuto dai pazienti iERM-A potrebbe indurre un GMT completo nelle cellule MIO-M1, i campioni iERM-B hanno causato solo un GMT parziale, caratterizzato dalla downregulation dei marker cellulari di Müller in assenza di upregulation di pro- marcatori fibrotici di miofibroblasti. Per la parte finale del mio lavoro di tesi, ho utilizzato il fluido vitreo ottenuto da pazienti con PDR come strumento per studiare l'attivazione che si verifica nelle cellule di Müller durante la PDR. I risultati mostrano che il vitreo PDR induce l'acquisizione di un fenotipo attivato nelle cellule di Müller, caratterizzato da un aumento della proliferazione e della migrazione cellulare, dall'attivazione del segnale intracellulare e dall'espressione di citochine/chemochine proinfiammatorie. Sorprendentemente, abbiamo scoperto che l'acquisizione di questo fenotipo non è correlata alla stimolazione del VEGF, mentre il trattamento delle cellule di Müller con il fattore di crescita dei fibroblasti di base (FGF2) induce un aumento significativo dell'espressione di varie citochine/chemochine nelle cellule MIO-M1. Di conseguenza, il farmaco anti-VEGF ranibizumab non influenza l'attivazione delle cellule di Müller mediata dal vitreo PDR mentre il trattamento con l'inibitore della tirosin-chinasi del recettore dell'FGF (FGFR) BGJ398, la trappola pan-FGF NSC12, l'antagonista della proteina legante l'eparina multi-target N- tert-butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe Boc2, o il farmaco antinfiammatorio idrocortisone inibisce, almeno in parte, l'attività dei campioni vitrei PDR. Insieme, i risultati indicano che potrebbe esistere una relazione tra la capacità del vitreo iERM di modulare il GMT nelle cellule di Müller, il profilo molecolare dei corrispondenti iERM e le caratteristiche cliniche dei pazienti iERM. Inoltre, questi dati indicano un ruolo per vari mediatori oltre al VEGF nella risposta suscitata dal vitreo PDR nelle cellule di Müller.
An epiretinal membrane (ERM) is a thin layer of fibrous tissue that can form on the surface of the retina macular area and cause vision problems. Müller glial cells appear to play a pivotal role in the pathogenesis of ERM, where various cytokines and growth factors may act as autocrine and paracrine modulators by triggering Müller cell proliferation, migration, collagen contraction, transdifferentiation, and increased expression of gliosis markers. Vitreous humor may represent a reservoir of pathological mediators that accumulate during the progression of retinal diseases. Here, the vitreous fluid obtained from iERM and PDR patients was used as a tool to investigate the activation that occurs in Müller cells in disease progression. During the first part of my Ph.D. thesis work, I participated in a research project in which we showed that surgically removed iERMs are characterized by a different pattern of expression of a series of the cell population, extracellular matrix, and cytokine/growth factor biomarkers relevant to the pathogenesis of the disease. Further, the hierarchical clustering of the gene expression data identified two molecular clusters of iERM membranes associated with distinct clinical and SD-OCT features (named iERM-A and iERM-B). iERM-A patients are characterized by less severe clinical features and a more "quiescent" iERM gene expression profile when compared to iERM-B patients. Further, I focused on understanding the role of Müller glial cells in the pathogenesis of iERM. During the progression of iERM, Müller glial cells undergo a glial-to-mesenchymal transition (GMT), a transdifferentiation process characterized by the downregulation of Müller cell markers paralleled by the upregulation of pro-fibrotic myofibroblast markers. The present study demonstrated that the vitreous fluid obtained from the iERM patients induces proliferation, migration, and GMT in MIO-M1 Müller cells, a phenotype consistent with Müller cell behaviour during iERM progression. However, even though the vitreous fluid obtained from iERM-A patients could induce a complete GMT in MIO-M1 cells, iERM-B samples caused only a partial GMT, characterized by the downregulation of Müller cell markers in the absence of upregulation of pro-fibrotic myofibroblast markers. For the final part of my thesis work, the vitreous fluid obtained from PDR patients was used as a tool to investigate the activation that occurs in Müller cells during PDR. The results show that PDR vitreous induces the acquisition of an activated phenotype in Müller cells, characterized by an increase in cell proliferation and migration, intracellular signalling activation, and proinflammatory cytokine/chemokine expression. Surprisingly, we found that the acquisition of this phenotype is not related to VEGF stimulation, whereas treatment of Müller cells with basic fibroblast growth factor (FGF2) induces a significant increase in the expression of various cytokines/chemokines in MIO-M1 cells. Accordingly, the anti-VEGF drug ranibizumab does not affect Müller cell activation mediated by PDR vitreous whereas treatment with the FGF receptor (FGFR) tyrosine kinase inhibitor BGJ398, the pan-FGF trap NSC12, the multi-target heparin-binding protein antagonist N-tert-butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe Boc2, or the anti-inflammatory drug hydrocortisone inhibits, at least in part,the activity of PDR vitreous samples. Together, the results indicate that a relationship may exist among the ability of iERM vitreous to modulate GMT in Müller cells, the molecular profile of the corresponding iERMs, and the clinical features of iERM patients. Also, these data point to a role for various mediators besides VEGF in the response elicited by PDR vitreous in Müller cells.

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BENCIVENNI, SERENA. "Glial cells and neuroinflammation: the adenosinergic contribution." Doctoral thesis, Università degli studi di Ferrara, 2018. http://hdl.handle.net/11392/2478763.

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Il segno distintivo del processo neuroinfiammatorio è l'attivazione delle microglia, le cellule immunocompetenti del sistema nervoso centrale (SNC), che sono responsabili del rilascio di numerosi mediatori pro-infiammatori implicati nella patogenesi di diverse malattie neurologiche come la malattia di Alzheimer, il morbo di Parkinson, la sclerosi multipla e l’ictus ischemico. Il recettore dell’immunità innata Toll-like (TLR)4, presente sulla superficie della microglia, gioca un ruolo chiave nella difesa dell'organismo e può essere attivato dal lipopolisaccaride (LPS), uno dei componenti della membrana cellulare esterna dei batteri gram-negativi. I recettori dell'adenosina (AR) interagendo con il recettore TLR4 influenzano numerose proprietà immunologiche delle cellule microgliali e sono implicati in molteplici stati fisiologici e patofisiologici nel SNC. Infatti, è stato dimostrato che l'adenosina (Ado), nucleoside ubiquitario con importanti funzioni immunomodulatorie e ligando endogeno degli AR, prende parte ai principali processi di attivazione della microglia come: proliferazione, estensione e retrazione dei processi cellulari, migrazione e produzione di citochine. Sulla base di queste considerazioni, lo scopo di questa tesi è stato quello di investigare il contributo adenosinergico sulla neuroinfiammazione mediata dalle cellule gliali attraverso l’analisi dell'espressione degli AR e le vie di trasduzione del segnale, i fattori di trascrizione e le citochine attivate da questi recettori in diverse condizioni patofisiologiche legate ad ipossia e infiammazione. Lo scopo dello studio riportato nel capitolo 1 è stato quello di investigare se Ado poteva influenzare le funzioni della microglia agendo sulla modulazione del fattore indotto dall’ipossia-1α (HIF-1α), il principale fattore di trascrizione dei geni ipossia-inducibili, coinvolti nella risposta immunitaria e regolati in normossia da mediatori dell'infiammazione. I dati ottenuti hanno messo in evidenza che Ado è in grado di aumentare l'accumulo di HIF-1α indotto dall’LPS portando ad un aumento dei geni bersaglio di HIF-1α coinvolti nel metabolismo cellulare e nell’eliminazione dei patogeni ma non è in grado di indurre quelli dipendenti da HIF-1α correlati all'angiogenesi e all'infiammazione. L'effetto stimolatorio di Ado su HIF-1α e dei suoi geni bersaglio è stato essenzialmente esercitato dall'attivazione degli A2A AR attraverso le proteine chinasi attivate da mitogeni (MAPK) chinasi regolate da segnali extra cellulari (ERK)1/2 e degli A2B AR tramite la MAPK p38 e la fosforilazione di Akt. Inoltre, Ado attraverso gli A2B AR ha aumentato i livelli del fattore di crescita dell'endotelio vascolare (VEGF) e diminuito quelli del fattore di necrosi tumorale (TNF)-α. Lo scopo dello studio riportato nel capitolo 2 è stato quello di indagare il potenziale ruolo degli AR nella modulazione della secrezione dell'interleuchina(IL)-6 e nella proliferazione cellulare in cellule microgliali murine primarie. I dati ottenuti hanno messo in evidenza che l'agonista A2B (BAY 60-6583) è in grado di stimolare l'aumento di IL-6, in modo dose e tempo-dipendente, sia in normossia che in ipossia e che tale aumento è fortemente ridotto dall’incubazione delle cellule con gli inibitori della fosfolipasi C (PLC), della proteina chinasi C (PKC)-ε e PKC-delta. Lo studio sulle vie di trasduzione del segnale cellulare ha rivelato che solo l'inibitore di p38 è in grado di bloccare l'effetto dell’agonista A2B sulla secrezione di IL-6, mentre gli inibitori di ERK1/2, JNK1/2 e Akt non hanno dato alcun effetto. La stimolazione di p38 da parte di BAY 60-6583 è risultata dipendente dagli A2B AR, tramite PLC, PKC-ɛ e PKC-delta ma non tramite l’adenilato ciclasi, sia in normossia che in ipossia. Infine, BAY 60-6583 ha aumentato la proliferazione delle cellule microgliali attraverso la via di segnale che vede coinvolti A2B AR, PLC, PKC-ε PKC-delta e p38.
The hallmark of neuroinflammation is the activation of microglia, the immunocompetent cells of the CNS, releasing a number of pro-inflammatory mediators implicated in the pathogenesis of several neurological diseases such as AD, PD, MS and ischemic stroke. The innate immune TLR4, localized on the surface of microglia, is a first-line host defense receptor against invading microorganisms and LPS, a component of the cell wall of gram-negative bacteria, was first identified as the TLR ligand. ARs interacting with TLR4 influence on many immune properties of microglia and are implicated in numerous physiological and pathophysiological states in CNS. Indeed, Ado, a ubiquitous nucleoside with important immunomodulatory functions, has been found to take part in the principal microglial activation processes spanning from proliferation, process extension, retraction, migration and cytokine production. On this background, the aim of this study was to investigate the adenosinergic contribution to glial cell mediated-neuroinflammation by analyzing the expression of ARs and the signalling pathways, transcription factors and cytokines activated by them in different pathophysiological conditions linked to hypoxic and inflammatory conditions. The aim of studies reported in chapter 1 was to investigate whether Ado may affect microglia functions by acting on HIF-1α modulation, the main transcription factor of hypoxia-inducible genes, involved in the immune response, being regulated in normoxia by inflammatory mediators. Primary murine microglia were activated with LPS with or without Ado, Ado receptor agonists and antagonists and HIF-1α accumulation and downstream genes regulation were determined. Ado increased LPS-induced HIF-1α accumulation leading to an increase in HIF-1α target genes involved in cell metabolism and pathogens killing but did not induce HIF-1α dependent genes related to angiogenesis and inflammation. The stimulatory effect of Ado on HIF-1α and its target genes was essentially exerted by activation of A2A through ERK1/2 (or p44/42) and A2B subtypes via p38 MAPKs and Akt phosphorylation. Furthermore, the nucleoside raised VEGF and decreased TNF-α levels, by activating A2B subtypes. Our results show that Ado increases GLUT-1 and iNOS gene expression in a HIF-1α-dependent way, through A2A and A2B ARs, suggesting their role in the regulation of microglial cells function following injury. However, inhibition of TNF-α adds an important anti-inflammatory effect only for the A2B subtype. The aim of studies reported in chapter 2 was to indagate the potential role of ARs in the modulation of IL-6 secretion and cell proliferation in primary microglial cells. The A2B AR agonist BAY 60-6583 stimulated IL-6 increase under normoxia and hypoxia, in a dose- and time-dependent way. In cells incubated with the blockers of PLC, PKC-ε and PKC-delta the IL-6 increase due to A2B AR activation was strongly reduced, whilst it was not affected by the inhibitor of AC. Investigation of cellular signalling involved in the A2B AR effect revealed that only the inhibitor of p38 MAPK was able to block the agonist effect on IL-6 secretion, whilst inhibitors of ERK1/2, JNK1/2 MAPKs and Akt were not. Stimulation of p38 by BAY 60-6583 was A2B AR dependent, through PLC, PKC-ɛ and PKC-delta but not AC pathway, in both normoxia and hypoxia. Finally, BAY 60-6583 increased microglial cell proliferation involving A2B AR, PLC, PKC-ε PKC-delta and p38 signalling. Our results show for the first time that Ado by activating A2B ARs increases IL-6 protein levels and cell proliferation through a pathway dependent on PLC, PKC-ε, PKC-delta, and p38 signalling. These findings add new molecular pathways activated by Ado in microglia to give a reduction of genes and cytokines involved in inflammation and hypoxic injury that may cohexist in stroke, ischemia and other CNS disorders.

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13

BOZZO, MATTEO. "Glial cells of the developing amphioxus: a molecular study." Doctoral thesis, Università degli studi di Genova, 2021. http://hdl.handle.net/11567/1043680.

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Glial cells play important roles in the development and homeostasis of metazoan nervous systems. However, while their involvement in the development and function in the central nervous system (CNS) of vertebrates is increasingly well understood, much less is known about invertebrate glia and the evolutionary history of glial cells more generally. An investigation into amphioxus glia is therefore timely, as this organism is the best living proxy for the last common ancestor of all chordates, and hence provides a window on the role of glial cells development and function at the transition between invertebrates and vertebrates. We report here our findings on amphioxus glia as characterized by molecular probes correlated with anatomical data at the TEM level. The results show amphioxus glial lineages express genes typical of vertebrate astroglia and radial glia and segregate early in development, forming what appears to be a spatially separated cell proliferation zone positioned laterally, between the dorsal and ventral zones of neural cell proliferation. Our study provides strong evidence for the presence of vertebrate-type glial cells in amphioxus while highlighting the role played by segregated progenitor cell pools in CNS development. There are implications also for our understanding of glial cells in a broader evolutionary context and insights into patterns of precursor cell deployment in the chordate nerve cord.

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De, Pascalis Chiara. "Role of intermediate filaments in collective cell migration of glial cells." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066026.

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Pendant la morphogenèse, la réparation des tissus et le cancer, les cellules peuvent migrer en manière mésenchymateuse et collective. Le cytosquelette est essentiel pour la migration, mais alors que l'actine et les microtubules ont été largement étudiés, le rôle des filaments intermédiaires (FIs) est encore largement inconnu. La déplétion des FI diminue souvant la vitesse de migration et les FI sont fréquemment surexprimé dans les tumeurs invasives. Pour ces propriétés, nous supposons que les FIs peuvent jouer un rôle clé dans la mécanique cellulaire pendant la migration.Pour étudier le rôle des FI dans la migration collective, nous avons utilisé des astrocytes, les principales cellules gliales du système nerveux central. Les astrocytes migrent collectivement pendant le développement et l'astrogliose en réponse à des signaux pathologiques ou traumatiques. Les astrocytes expriment trois principales FI cytoplasmiques: nestine, GFAP (protéine acide fibrillaire fibreuse) et vimentine, qui forment un réseau dense. Les FI sont surexprimé pendant l'astrogliose et dans les glioblastomes, des tumeurs cérébrales hautement invasives et létales. On ignore si la surexpression des FI est responsable de l'invasion du glioblastome.Au cours de la migration collective dans un test de blessure, les FI contrôlent le positionnement du noyau, la polarité et la migration. On montre que les FI régulent la migration collective dirigée de manière dépendante de la rigidité. Ils agissent avec la protéine connecteur cytoplasmique plectine pour contrôler les point focaux et les jonctions adhérentes. Les FI contrôlent la dynamique et l'organisation de l'actine et régulent la distribution des tractions cellulaires et des contraintes dans la monocouche migrante. Ces résultats démontrent le rôle crucial des FI dans les propriétés mécaniques des cellules migrantes
During morphogenesis, tissue repair and cancer, cells can migrate in a mesenchymal and collective manner. The cytoskeleton is essential for migration, but whereas actin and microtubules have been extensively studied, the role of intermediate filaments (IFs) is still largely unknown. IF depletion generally decreases migration speed and IF proteins are frequently found upregulated in invasive tumours. Because of IF properties, we hypothesise that they may be key players in cell mechanics during migration. To study the role of IFs in collective migration we used astrocytes, the main glial cells of the central nervous system. Astrocytes migrate collectively during development and astrogliosis in response to pathological or traumatic signals. Astrocytes express three main cytoplasmic IFs: nestin, GFAP (Glial Fibrillary Acidic Protein) and vimentin, which form a dense network. IF proteins are upregulated during astrogliosis and glioblastomas, highly invasive and lethal brain tumours. Whether upregulation of IFs is responsible for glioblastoma invasion is still unknown. During wound-induced collective migration, IFs control nuclear positioning, polarisation and migration. We found that IFs regulate collective directed migration in a stiffness-dependent manner. They act in concert with the cytolinker protein plectin to control focal adhesions and adherens junctions. IFs control actin dynamics and organisation and regulate the distribution of cell tractions and stresses across the migrating cell monolayer. These results demonstrate the crucial role of IFs in the mechanical properties of migrating cells

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15

De, Pascalis Chiara. "Role of intermediate filaments in collective cell migration of glial cells." Electronic Thesis or Diss., Paris 6, 2017. http://www.theses.fr/2017PA066026.

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Pendant la morphogenèse, la réparation des tissus et le cancer, les cellules peuvent migrer en manière mésenchymateuse et collective. Le cytosquelette est essentiel pour la migration, mais alors que l'actine et les microtubules ont été largement étudiés, le rôle des filaments intermédiaires (FIs) est encore largement inconnu. La déplétion des FI diminue souvant la vitesse de migration et les FI sont fréquemment surexprimé dans les tumeurs invasives. Pour ces propriétés, nous supposons que les FIs peuvent jouer un rôle clé dans la mécanique cellulaire pendant la migration.Pour étudier le rôle des FI dans la migration collective, nous avons utilisé des astrocytes, les principales cellules gliales du système nerveux central. Les astrocytes migrent collectivement pendant le développement et l'astrogliose en réponse à des signaux pathologiques ou traumatiques. Les astrocytes expriment trois principales FI cytoplasmiques: nestine, GFAP (protéine acide fibrillaire fibreuse) et vimentine, qui forment un réseau dense. Les FI sont surexprimé pendant l'astrogliose et dans les glioblastomes, des tumeurs cérébrales hautement invasives et létales. On ignore si la surexpression des FI est responsable de l'invasion du glioblastome.Au cours de la migration collective dans un test de blessure, les FI contrôlent le positionnement du noyau, la polarité et la migration. On montre que les FI régulent la migration collective dirigée de manière dépendante de la rigidité. Ils agissent avec la protéine connecteur cytoplasmique plectine pour contrôler les point focaux et les jonctions adhérentes. Les FI contrôlent la dynamique et l'organisation de l'actine et régulent la distribution des tractions cellulaires et des contraintes dans la monocouche migrante. Ces résultats démontrent le rôle crucial des FI dans les propriétés mécaniques des cellules migrantes
During morphogenesis, tissue repair and cancer, cells can migrate in a mesenchymal and collective manner. The cytoskeleton is essential for migration, but whereas actin and microtubules have been extensively studied, the role of intermediate filaments (IFs) is still largely unknown. IF depletion generally decreases migration speed and IF proteins are frequently found upregulated in invasive tumours. Because of IF properties, we hypothesise that they may be key players in cell mechanics during migration. To study the role of IFs in collective migration we used astrocytes, the main glial cells of the central nervous system. Astrocytes migrate collectively during development and astrogliosis in response to pathological or traumatic signals. Astrocytes express three main cytoplasmic IFs: nestin, GFAP (Glial Fibrillary Acidic Protein) and vimentin, which form a dense network. IF proteins are upregulated during astrogliosis and glioblastomas, highly invasive and lethal brain tumours. Whether upregulation of IFs is responsible for glioblastoma invasion is still unknown. During wound-induced collective migration, IFs control nuclear positioning, polarisation and migration. We found that IFs regulate collective directed migration in a stiffness-dependent manner. They act in concert with the cytolinker protein plectin to control focal adhesions and adherens junctions. IFs control actin dynamics and organisation and regulate the distribution of cell tractions and stresses across the migrating cell monolayer. These results demonstrate the crucial role of IFs in the mechanical properties of migrating cells

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16

Gale, Zoe. "Glial cell line-derived neurotrophic factor effects on dental pulp cells and osteoblast-like cells." Thesis, University of Birmingham, 2012. http://etheses.bham.ac.uk//id/eprint/3268/.

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Glial cell line-derived neurotrophic factor (GDNF) is a growth factor promoting survival, proliferation and differentiation of neural crest cells. Neural crest cells play an important role within mesenchymal tissues during dental pulp and calvarial bone development. GDNF also has a role within non-neuronal tissues and is expressed during dental development. GDNF null mutations prevent the formation of the mineralised hard tissues of the tooth. The hypothesis for this study was that GDNF affects mesenchymal dental pulp cells (DPC), promoting the regenerative responses of mineralised tissues. This study utilised cell culture models to investigate the direct effects of GDNF on the proliferation and differentiation of dental pulp cells, bone marrow mesenchymal stromal/stem cells (BMSC) and calvarial osteoblasts. This research demonstrated that these culture models expressed GDNF and its receptors GFR\(\alpha\)1 and RET. GDNF was shown to directly stimulate DPC and osteoblast-like cell proliferation and differentiation. Moreover, GDNF was cytoprotective when DPCs were cultured under conditions reflecting aspects of inflammation, which may occur during repair. These conditions included supplementation with the pro-inflammatory cytokine TNF\(\alpha\) and culture under serum-starved conditions. It is proposed that GDNF may play an important regulatory role in dental pulp homeostasis and bone metabolism.

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Cotterill, Claire Louise. "Semliki Forest virus-induced apoptosis in glial cells." Thesis, University of Edinburgh, 2005. http://hdl.handle.net/1842/29712.

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Multiple sclerosis (MS) is the most common neurological disease affecting young adults. The incidence rates in Scotland are among the highest in the world. Virus infection may have a precipitating role, or exacerbate symptoms. That viruses can produce inflammatory central nervous system (CNS) demyelinating disease has been well established from study of several natural and experimental infections; one model system is Semliki Forest virus (SFV) infection of mice. SFV infection of BALB/c mice infected at less than 12 days of age (P12) causes fulminant encephalitis, characterised by apoptotic death of neuronal cell populations. In contrast, virus-infected neurons in mice older than P14 survive. In immunocompetent animals lesions of inflammatory demyelination develop. In immunocompromised animals (for example nu/nu mice) virus persists but no lesions of demyelination develop. SFV had previously been observed to trigger apoptosis in numerous proliferating cell lines and in immature differentiating neuronal cell cultures. One explanation for the dichotomy in the outcome of neuronal infection is that levels of key pro- or anti-apoptotic proteins differ as a function of maturational state. Oligodendrocytes are infected by SFV but little is known about the outcome of infection in these cells. The absence of demyelination in immunocompromised animals suggests these cells can survive infection. The aim of this thesis is to determine the fate of oligodendrocytes upon SFV infection, to ascertain the nature of any cell death and, if observed, to determine whether this is dependent on cell maturation state. Three experimental systems are used; glial cell lines, mixed glial cell cultures, and tissue sections from infected adult BALB/c and nu/nu mice. Two differentiation-inducible oligodendrocyte-type-2 astrocyte (0-2A) progenitor cell lines, SS5 and BC30, were utilised. 0-2A progenitor cells died rapidly of apoptosis as determined by DAPI labelling, DNA fragmentation and morphological features such as cell blistering and cell blebbing. Differentiation delayed virus induced cell death between 12 and 24 hours but did not prevent it: again cell death occurred by apoptosis. The outcome of SFV infection of oligodendroglia derived from mixed primary cultures was dependent on the degree of cellular homogeneity. Immunocytochemical studies revealed that immature 0-2A progenitors died rapidly, as revealed by double staining for caspase-3 and early 0-2A cell markers. The susceptibility of mature oligodendrocytes was found to be dependent on cellular environment. Mature oligodendrocytes were equally susceptible to virus-induced apoptosis as immature progenitors when cultured in isolation i.e. as enriched purified populations. On the contrary, cultures of mature oligodendrocytes maintained in the presence of other glial cells, or in contact with extracellular matrix molecules present in vivo, survived infection for the period under study: two weeks. The fate of the mature oligodendrocyte was further investigated in the corpus callosum in vivo using sections from SFV-infected adult BALB/c and nu/nu mice. Dual immunolabelling for virus and apoptosis (TUNEL staining) revealed an active period of cell death between PID 4 and 6. Dual immunofluorescence for 2'/-3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and SFV or caspase-3 visualised by confocal microscopy indicated that although mature oligodendrocytes were infected with SFV they did not die by apoptosis. In conclusion, this study presents evidence that isolated enriched cultures of mature oligodendrocytes are susceptible to apoptosis as are their immature counterparts. Paradoxically, mature oligodendrocytes studied in vivo or maintained in the presence of other glial cells factors in vitro, did not undergo virus-induced apoptosis, unlike their immature relatives.

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18

Bianco, F. "The role of P2X7 receptor in glial cells." Doctoral thesis, Università degli Studi di Milano, 2007. http://hdl.handle.net/2434/63133.

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Summary of thesis The aim of this study was to study the functional consequences of the ATP mediated communication between astrocytes and microglia, with particular emphasis on the functional consequences related to the activation of purinergic receptor P2X7 on microglial cells. The results obtained indicate that: 1. that the LPS-induced reduction of functional P2X7 receptor in embryonic microglia may mediate the cell cycle modifications observed upon exposure to the endotoxin. 2. the release of at least a fraction of IL 1-beta from microglia takes place, upon ATP stimulation, through the shedding of vesicles from the plasmamembrane. Shed vesicles appear to be the site of IL 1-beta processing. 3. that intercellular calcium mediated signalling might contribute in cortex more than in the hippocampus to the propagation and maintenance of an inflammatory state. Most importantly, the present study represents the first evidence of microvesicle shedding in the CNS. Just like their systemic counterpart (monocytes) microglial cells are able to form vesicle and release them in a calcium-dependent manner. We have demonstrated that vesicle contain protein elements and that biological processes such as IL 1-beta maturation can occur inside isolated vesicles.

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19

Göritz, Christian. "Influence of glial cells on postnatal differentiation of rat retinal ganglion cells." [S.l. : s.n.], 2005. http://www.diss.fu-berlin.de/2005/65/index.html.

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20

Göritz, Christian. "Influence of glial cells on postnatal differentiation of rat retinal ganglion cells." Université Louis Pasteur (Strasbourg) (1971-2008), 2005. https://publication-theses.unistra.fr/public/theses_doctorat/2005/GORITZ_Christian_2005.pdf.

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Jacques, Cécile. "Etude du rôle et du mécanisme d'action des facteurs de transcription glial cell deficient/glial cells missing au cours du développement." Université Louis Pasteur (Strasbourg) (1971-2008), 2007. https://publication-theses.unistra.fr/public/theses_doctorat/2007/JACQUES_Cecile_2007.pdf.

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Les facteurs de transcription Gcm et Gcm2 sont connus pour leur rôle de déterminants gliaux et plasmatocytaires chez l’embryon de drosophile. Lors de ma thèse, j’ai mis en évidence que les gènes gcm-gcm2 sont requis pour la différenciation terminale d’une sous-population de cellules tendon. Par la suite, nous avons montré que l’orthologue c-GCM1 chez le poulet est requis lors de l’embryogenèse pour la différenciation des précurseurs neuraux de la moelle épinière en neurones. De façon surprenante, nous avons également mis en évidence que les gènes de type gcm sont exprimés et requis dans des lignages neuronaux du cerveau de la drosophile aux stades post-embryonnaires. Toutes ces études nous ont permis de montrer que le rôle spécifique des facteurs de transcription Gcm dépend du contexte cellulaire où ils sont exprimés. Un crible double-hybride m’a permis l’identification du cofacteur dpias et son étude m’a permis de montrer une implication de Gcm au cours l’hématopoïèse larvaire
Gcm-Gcm2 transcription factors are known for their role in glial and plasmatocytes differentiation in Drosophila embryo. During my PhD, I have shown that gcm-gcm2 genes are required for terminal differentiation of a subpopulation of tendon cells. Thereafter, we showed that the chicken c-GCM1 orthologue is required during embryogenesis for the differentiation of spinal cord neural precursors into neurons. We have also shown that gcm genes are expressed and required in post-embryonic neural brain lineages of Drosophila. All these studies show that the specific role of Gcm transcription factors depends on the cellular context in which they are expressed. A two hybrid screen enabled me to identify the cofactor dpias and its study has allowed me to show the implication of Gcm in larval hematopoiesis

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Jacques, Cécile Giangrande Angela. "Étude du rôle et du mécanisme d'action des facteurs de transcription Glial cell deficient/Glial cells missing au cours du développement." Strasbourg : Université de Strasbourg, 2009. http://eprints-scd-ulp.u-strasbg.fr:8080/1139/01/JACQUES_Cecile_2007.pdf.

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23

Blackburn, Daniel J. "The role of glial cells in motor neuron disease." Thesis, University of Sheffield, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.531123.

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24

Acton, David. "Regulation of mammalian spinal locomotor networks by glial cells." Thesis, University of St Andrews, 2017. http://hdl.handle.net/10023/10133.

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Networks of interneurons within the spinal cord coordinate the rhythmic activation of muscles during locomotion. These networks are subject to extensive neuromodulation, ensuring appropriate behavioural output. Astrocytes are proposed to detect neuronal activity via Gαq-linked G-protein coupled receptors and to secrete neuromodulators in response. However, there is currently a paucity of evidence that astrocytic information processing of this kind is important in behaviour. Here, it is shown that protease-activated receptor-1 (PAR1), a Gαq-linked receptor, is preferentially expressed by glia in the spinal cords of postnatal mice. During ongoing locomotor-related network activity in isolated spinal cords, PAR1 activation stimulates release of adenosine triphosphate (ATP), which is hydrolysed to adenosine extracellularly. Adenosine then activates A1 receptors to reduce the frequency of locomotor-related bursting recorded from ventral roots. This entails inhibition of D1 dopamine receptors, activation of which enhances burst frequency. The effect of A1 blockade scales with network activity, consistent with activity-dependent production of adenosine by glia. Astrocytes also regulate activity by controlling the availability of D-serine or glycine, both of which act as co-agonists of glutamate at N-methyl-D-aspartate receptors (NMDARs). The importance of NMDAR regulation for locomotor-related activity is demonstrated by blockade of NMDARs, which reduces burst frequency and amplitude. Bath-applied D-serine increases the frequency of locomotor-related bursting but not intense synchronous bursting produced by blockade of inhibitory transmission, implying activity-dependent regulation of co-agonist availability. Depletion of endogenous D-serine increases the frequency of locomotor-related but not synchronous bursting, indicating that D-serine is required at a subset of NMDARs expressed by inhibitory interneurons. Blockade of the astrocytic glycine transporter GlyT1 increases the frequency of locomotor-related activity, but application of glycine has no effect, indicating that GlyT1 regulates glycine at excitatory synapses. These results indicate that glia play an important role in regulating the output of spinal locomotor networks.

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TESTA, FRANCESCA. "EVALUATION OF rHIgM22 EFFECT ON MIXED GLIAL CELLS CULTURE." Doctoral thesis, Università degli Studi di Milano, 2018. http://hdl.handle.net/2434/543913.

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Multiple sclerosis (MS), considered the lead disease featuring demyelination, is the most common cause of non traumatic disability in young people. It is characterized by inflammation, progressive demyelination and gliosis, axonal injury and loss. The pathological hallmarks of all the subtypes of this disease are focal areas, called plaques, of demyelination in the CNS, with surrounding inflammation and neurodegeneration. Despite its high prevalence, multiple sclerosis remains a challenging ailment to study. Currently the most widely accepted hypothesis concerning MS pathogenesis is the autoimmune hypothesis: an autoimmune inflammation is proposed to be the cause of demyelination and auto-reactive leukocytes could be the disease initiators. One of the therapeutic approaches that is currently being developed to improve the regenerative outcome involves the use of CNS reactive antibodies to promote remyelination. One of these antibodies, rHIgM22, is able to bind to oligodendrocytes and myelin in vitro. Moreover, rHIgM22 is able to enter the CNS, accumulate at lesion site and promote remyelination in mouse models of chronical demyelination. As a matter of fact, this antibody has recently passed a phase I clinical trial for treatment of MS. Evidence suggests that the binding target of rHIgM22 could be associated with plasma membrane lipid rafts, and that lipid rafts might be involved in the signaling associated with the biological activity of this antibody. Moreover, it has been demonstrated that, isolated OPCs do not respond to rHIgM22 treatment, instead mixed glial cultures consisting of astrocytes, OPCs and microglial cells demonstrate observable rHIgM22-mediated OPC proliferation. The aim of this study was to analyze the plasma membrane lipid rafts composition in MGC in order to evaluate the effects exerted by rHIgM22 on these cells after single dose treatment of various duration. The analysis of the lipids and proteins distribution in MGC fractions, obtained after discontinuous sucrose gradient centrifugation of cells, and the alteration on lipids and protein composition of MGC due to the rHIgM22 treatment have been tested using TLC immunostaining assays and western blot analysis. The results obtained show that the DRM fraction obtained from MGC was enriched in sphingolipids, in particular sphingomyelin and gangliosides together with Lyn, Caveolin 1 and PrP(SAF32). On the contrary, phospholipids, in particular phosphatididylethanolamine and phosphatidic acid are enriched in the HD fraction, together with integrin αv and Akt. Furthermore we observed that rHIgM22 exerted an effect on the expression of P-Src(Y416) family and Lyn, that show a significant decrease, and PDGFRα that shows a significant increase. Moreover, the rHIgM22 treatment also induces a decrease in the activity of the aSMase. We hypothesize that the treatment with IgM22 could elicit biological responses mediated by alterations of lipid-dependent membrane organization which result in a reorganization of Lyn, integrin αvβ3 and PDGFRα at the cell surface to form a signaling complex. The formation of this complex triggers Lyn activation which in turn promotes oligodendrocyte precursor cells (OPCs) survival and proliferation and an inhibition of the pro apoptotic signaling. Moreover, the increased activation of Lyn could determine a decrease in ASMase activity and consequently in ceramide generation, thus inhibiting pro-apoptotic signaling and/or organization of sphingolipid-dependent signaling platforms. The identification of the binding targets of this antibody, able to promote remyelination in validated mouse models of MS, and the characterization of their membrane microenvironment could significantly contribute to the reveal the signaling mechanisms underlying the biological activity of rHIgM22.

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Mallick, Ali Sameer. "Stem cell therapies for sensorineural hearing loss : understanding the role of glial cells." Thesis, University of Sheffield, 2017. http://etheses.whiterose.ac.uk/19788/.

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Delbaz, Seyed Ali. "Multi-nucleated glial cells and the implication for neural health." Thesis, Griffith University, 2017. http://hdl.handle.net/10072/379570.

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The term glioma encompasses all tumours that originate from glial cells and accounts for almost 80% of primary malignant brain tumours. Gliomas typically present as a heterogeneous mass of cells that include the presence of multi-nucleated cells. Infectious agents are a significant risk factor in gliomagenesis and brain cancer, particularly those agents that are known to cause multi-nucleation of cells. To date, the infectious agents that have been implicated in gliomagenesis include viruses, protozoans, and possibly Brucella species. However, there is currently no evidence of bacteria directly causing multi-nucleation of glia resulting in gliomagenesis. The bacteria Burkholderia pseudomallei and Neisseria meningitidis, the causative agents of melioidosis and meningitis respectively can penetrate the central nervous system (CNS) via infection of the olfactory and trigeminal nerves. Importantly, the penetration of the CNS by B. pseudomallei and N. meningitidis can occur at very low bacterial levels such that CNS infection can be asymptomatic, and the bacteria can persist within the body for many years or even decades. The effect of long-term presence of subclinical levels of the bacteria within the CNS is unknown and B. pseudomallei and N. meningitidis infections have not yet been implicated in gliomagenesis. The in vitro work in our laboratory has determined that B. pseudomallei rapidly initiates the formation of multinucleated glial cells, including olfactory ensheathing cells (OECs), Schwann cells and astrocytes. These results suggest that the bacteria may initiate a cascade of events leading to multi-nucleation of glial cells; as multi-nucleated cells are a pathology that is a characteristic of glioma it raises the question of whether the glia cells exhibit other characteristics associated with inflammation and/or glioma. The goal of this thesis is to characterise the cellular and molecular events resulting from bacterial initiation of multi-nucleated glial cells. The project consists of three aims. The first aim is the study of multinucleated cell (MNC) formation in Schwann cells after infection with B. pseudomallei and N. meningitidis serogroup B in vitro. The second aim is to determine the changes in the expression of molecules associated with gliomagenesis in multinucleated glial cells. The third aim is to study the energy production in Schwann cells following the infection with B. pseudomallei. Trigeminal Schwann cells were infected with B. pseudomallei and N. meningitidis serogroup B in various ratios and formats and examined for formation of MNCs. The immunofluorescence microscopy results showed that Schwann cells formed MNCs following the infection with both bacteria. The results also demonstrated that infection with both bacteria is associated with the expression of proteins and markers associated with inflammation and glioma. Immunoblotting, proteomics and qRT-PCR results showed that the expression of inflammatory and gliomagenesis markers were upregulated significantly after the infection with B. pseudomallei and N. meningitidis serogroup B. These results suggest that the bacterial infection of glia leads to responses consistent with inflammation and/or initiation of gliomagenesis. We also demonstrated that B. pseudomallei infection can mis-regulate the expression of Warburg effect genes in favour of aerobic glycolysis energy production which is a characteristic feature of carcinogenesis. In conclusion, in this study we showed that infection of glia with facultative intracellular bacteria such as B. pseudomallei and N. meningitidis results in molecular and cellular changes consistent with inflammatory responses and potentially associated with glioma.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Environment and Sc
Science, Environment, Engineering and Technology
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28

Downing, Trevor. "THE RELATIONSHIP BETWEEN LACTIC ACID, REACTIVE OXYGEN SPECIES AND THE HYPOXIA-INDUCED ACIDIFICATION SEEN IN CHEMOSENSITIVE NEURONS OF THE NUCLEUS TRACTUS SOLITARIUS (NTS)." Wright State University / OhioLINK, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=wright1158455199.

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TIBERI, ALEXIA. "A glial side to the neurotrophin field: studying the effects of neurotrophins on glial cells in the CNS." Doctoral thesis, Scuola Normale Superiore, 2020. http://hdl.handle.net/11384/94548.

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Sinclair, Michael S. "Modulation of Peripheral Taste Function by Glial-like Taste Cells." Scholarly Repository, 2012. http://scholarlyrepository.miami.edu/oa_dissertations/715.

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Taste is detected by cells of taste buds in the oral cavity. Mammalian taste buds contain three types of cells: receptor, presynaptic, and glial-like. Of these three, glial-like cells are the least studied. Their only known function is that they clear neurotransmitters from the extracellular space. The present work describes two previously undocumented properties of glial-like cells. First, Oxytocin receptor (OXTR) mRNA was detected by RT-PCR in taste tissue of mice. In the taste buds of Oxtr-YFP knockin mice, YFP was seen in glial-like taste cells and other cells immediately outside the taste bud, but no other cells in oral epithelium. Oxytocin (OXT) elicited Ca2+ responses from cells that resemble glial-like taste cells (by criteria including gene expression and lack of excitability). The EC50 for OXT in these cells was 33 nM, and responses saturated at 1 µM. 500 nM L-371,257 (an OXTR antagonist) significantly inhihited the responses to OXT. In a semi-intact preparation of lingual slices, OXT did not alter bitter tastant-evoked Ca2+ responses. Further, in behavioral studies, OXT (10 mg/kg i.p.) did not alter the responses of mice to aversive salty (NaCl), bitter (quinine), or sour (citric acid) solutions. In contrast, OXT (0.1 mg/kg i.p.) significantly decreased taste behavioral responses to low-to-intermediate concentrations of sucrose. My data suggest that OXT may modulate sweet taste sensitivity in vivo by acting on glial-like cells in taste buds. Second, Renal Outer Medullary K channel (ROMK) mRNA was also detected by RT-PCR in taste buds . Immunostaining revealed that ROMK is localized to the apical tips of glial-like taste cells. In the kidney, ROMK, apically localized in nephron epithelium facilitates a unidirectional flow (i.e. excretion) of K+. I suggest that, analogous to glia in the central nervous system, glial-like taste cells homeostatically redistribute extracellular [K+ ] within taste buds to maintain their sensitivity. The results of this study reveal that glial-like taste cells resemble nervous system glia in more ways than simply clearing neurotransmitters. They may also modulate the sensory output of the taste bud and buffer the extracellular [K+]. A more active role for glial-like cells in the functioning of the taste bud should be investigated.

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Köritzer, Julia. "Biophysical effects of cold atmopheric plasma on glial tumor cells." Diss., Ludwig-Maximilians-Universität München, 2013. http://nbn-resolving.de/urn:nbn:de:bvb:19-162120.

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32

Keen, Leigh John. "The growth and pharmacology of insect glial cells in vitro." Thesis, Oxford Brookes University, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359837.

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Smith, Peter Michael. "Investigations into the myelinating capability of transplanted porcine glial cells." Thesis, University of Cambridge, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.624554.

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Ng, Wai Yee. "Ginsenosides on the growth and proliferation of glial tumor cells." HKBU Institutional Repository, 2008. http://repository.hkbu.edu.hk/etd_ra/998.

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De, Simone Francesca Isabella. "Neuroimmune regulation of JCV by immune mediators in glial cells." Doctoral thesis, Universita degli studi di Salerno, 2015. http://hdl.handle.net/10556/2045.

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2012 - 2013
The human polyomavirus JC (JCV) is a small DNA virus responsible for the initiation of progressive multifocal leukoencephalopathy (PML), an often lethal disease of the brain characterized by lytic infection of oligodendrocytes in the central nervous system (CNS). Patients undergoing immune modulatory therapies for the treatment of autoimmune diseases such as multiple sclerosis, and individuals with an impaired-immune system, most notably AIDS patients, are in the high risk group of developing PML. Previous studies suggested that soluble immune mediators secreted from PBMCs inhibited viral genomic replication. However little is known regarding the molecular mechanism of this regulation. Here we investigated the impact of conditioned media (CM) from activated PBMCs on viral replication and gene expression by molecular virology techniques. Our data showed that viral gene expression as well as viral replication was suppressed by the CM. Further studies revealed that soluble immune mediators from PBMCs possessed a dual control on T-antigen expression at transcription and post-transcription level. These observations demonstrate a novel role of immune mediators in regulation of JCV gene expression, and provide a new avenue of research to understand molecular mechanism of viral reactivation in patients who are at risk of developing PML. [edited by author]
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36

Tassoni, Alessia. "Retinal glial responses to mesenchymal stem cell transplantation." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.709042.

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Dean, Charlotte Hannah. "The transcription factors dHAND and eHAND and the growth factor HGF are involved in peripheral nervous system development." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.367740.

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Davis, Hedvika. "Glial differentiation of human umbilical stem cells in 2D and 3D environments." Doctoral diss., University of Central Florida, 2011. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/4931.

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During differentiation stem cells are exposed to a range of microenvironmental chemical and physical cues. In this study, human multipotent progenitor cells (hMLPCs) were differentiated from umbilical cord into oligodendrocytes and astrocytes. Chemical cues were represented by a novel defined differentiation medium containing the neurotransmitter norepinephrine (NE). In traditional 2 dimensional (2D) conditions, the hMLPCs differentiated into oligodendrocyte precursors, but did not progress further. However, in a constructed 3 dimensional (3D) environment, the hMLPCs differentiated into committed oligodendrocytes that expressed MBP. When co-cultured with rat embryonic hippocampal neurons (EHNs), hMLPCs developed in astrocytes or oligodendrocytes, based on presence of growth factors in the differentiation medium. In co-culture, physical cues provided by axons were essential for complete differentiation of both astrocytes and oligodendrocytes. This study presents a novel method of obtaining glia from human MLPCs that could eliminate many of the difficulties associated with their differentiation from embryonic stem cells. In addition, it reveals the complex interplay between physical cues and biomolecules on stem cell differentiation.
ID: 029808916; System requirements: World Wide Web browser and PDF reader.; Mode of access: World Wide Web.; Thesis (Ph.D.)--University of Central Florida, 2011.; Includes bibliographical references (p. 77-86).
Ph.D.
Doctorate
Burnett School of Biomedical Sciences
Medicine
Biomedical Sciences

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39

Franceschini, Isabelle A. "Cellular and molecular studies on olfactory bulb ensheathing cells." Thesis, University of Glasgow, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301803.

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Wahl, Vincent. "Wirkung von Osteopontin auf die osmotische Volumenregulation von Müller- und Bipolarzellen der Rattennetzhaut." Doctoral thesis, Universitätsbibliothek Leipzig, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-198550.

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Die Arbeit befasst sich mit dem Anschwellen von Neuronen und Gliazellen der Netzhaut, was einen wichtigen pathogenetischen Faktor des Netzhautödems darstellt. Osteopontin ist ein neuroprotektiver Faktor, der durch GDNF-Stimulation (glial cell line-derived neurotrophic factor) aus Müllerzellen ausgeschüttet wird. Die durch Osteopontin vermittelte Inhibition der osmotischen Zellschwellung von Müllerzellen der Ratte in Anwesenheit von Bariumionen oder H2O2 wird beschrieben und es wird dargestellt, dass Osteopontin keinen Einfluss auf die osmotische Zellschwellung der Bipolarzellen hat. Der für Müllerzellen beschriebene Effekt war dosisabhängig mit einer mittleren effektiven Konzentration von ca. 0,6 ng/ml. Durch den Einsatz pharmakologischer Rezeptor- oder Enzymblocker bzw. Antikörper werden die Schritte der Osteopontinwirkung identifiziert. Osteopontin induziert die Freisetzung von VEGF, Glutamat, ATP und Adenosin aus Müllerzellen. Die Osteopontinwirkung wurde verhindert durch die Blockade von spannungsabhängigen Natriumkanälen, T-Typ Calciumkanälen, Kalium- und Chloridkanälen. Der Effekt ist außerdem abhängig von einem intrazellulären Calciumsignal, der Aktivierung der Phospholipase C und der Proteinkinase C und der vesikulären Exozytose von Glutamat. Die Arbeit kommt zu dem Schluss, dass der neuroprotektive Effekt von Osteopontin teilweise durch das Verhindern eines Anschwellens der Müllerzellen und durch die Induktion einer Freisetzung von VEGF und Adenosin vermittelt wird.

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41

Chen, Mo. "Natural products and glial cell therapy for repairing the nervous system." Thesis, Griffith University, 2019. http://hdl.handle.net/10072/389731.

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The problem: In Australia, over 12,000 people live with a spinal cord injury (SCI) and at least one new case occurs every day. Currently, there is no effective treatment for SCI. Transplantation of olfactory ensheathing cells (OECs; the glial cells of the primary olfactory nervous system) is a promising therapy, in particular autologous transplantation. OECs exhibit unique properties which stimulate neuronal growth and axonal extension, including structural and neurotrophic/guidance support. OECs also function as immune cells and remove (phagocytose) cell debris from the injury site. Furthermore, OECs migrate across the injury site and provide support for regenerating axons. However, functional outcomes in both animal studies and human clinical trials vary greatly, and there are key obstacles in this therapy. These include insufficient cell proliferation rate (both prior to transplantation and after transplantation), cell migration rate and phagocytic activity. If these cell behaviours could be stimulated, the therapeutic potential of OECs would be significantly enhanced. Another important avenue for improvement is the development of novel three-dimensional (3D) cell constructs suitable for both pre-transplantation work (cell culture and drug screening) and for transplantation of OECs directly as a 3D structure into the nervous system injury site. In summary, this work has (1) identified three natural compounds with potential to promote favourable OEC behaviours relevant for neural repair, and (2) led to the development of a novel 3D culture system in which cells rapidly self-assemble without any added ingredients, applicable to a wide range of neural repair avenues. Thus far, the outcomes of this thesis have led to two patent applications, two first-author publications, three first-author manuscripts in submission/preparation, and 1 patent application in preparation, as well as contributing to four papers/manuscripts led by other researchers in the Clem Jones Centre for Neurobiology and Stem Cell Research. The future directions towards enhancing the outcomes of OEC transplantation will be based on the combination of the identified natural products and the developed NLM/NLMNB 3D cell culture methods.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Environment and Sc
Science, Environment, Engineering and Technology
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42

Vrotsos, Emmanuel George. "MCP-1 and APP involvement in glial differentiation and migration of neuroprogenitor cells." Orlando, Fla. : University of Central Florida, 2009. http://purl.fcla.edu/fcla/etd/CFE0002517.

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43

李勝修 and Shengxiu Li. "The role of glial cells in the survival and axonal regeneration of retinal ganglion cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1998. http://hub.hku.hk/bib/B31238932.

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Li, Shengxiu. "The role of glial cells in the survival and axonal regeneration of retinal ganglion cells /." Hong Kong : University of Hong Kong, 1998. http://sunzi.lib.hku.hk/hkuto/record.jsp?B20897650.

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45

Teare, Katrina Anne. "Designing a delivery system for glial cells for spinal cord repair." Thesis, University of Nottingham, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.428927.

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46

Lawton, Michelle. "The effect of heavy metals on differentiated neuronal and glial cells." Thesis, Nottingham Trent University, 2007. http://irep.ntu.ac.uk/id/eprint/219/.

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Heavy metal poisoning poses a serious health risk among populations worldwide. The symptoms presented by exposure are varied and depend upon the species of the metal, the age of the individual and the exposure dose. All heavy metals have debilitating effects on the CNS. Children are especially sensitive to the neurological effects due to the intense growth and activity of a developing nervous system and inadequately developed defences. The aims of this study were to determine the effects of sub-lethal concentrations of numerous heavy metals on neuronal and glial cell differentiation. Using established cellular models, the toxicity of zinc, lead, mercury, methylmercury and thimerosal were investigated using assays of cell viability and morphology on differentiating N2a and C6 cells. Initial research revealed thimerosal, methylmercury and cadmium to be the most toxic compounds tested, in terms of their ability to inhibit the outgrowth of neurites in both cell lines at sub-lethal concentrations. Although cadmium chloride showed similar patterns of toxicity to the mercury compounds, thimerosal and MeHgCl were chosen for further investigation at a molecular level. Methylmercury chloride a common environmental pollutant and thimerosal; a preservative found in many medicines, were chosen for further investigation, as previous work has demonstrated the health risks posed by the two organic mercury compounds but little is known about non-lethal changes that occur in the nervous system, especially with thimerosal. Both thimerosal and MeHgCl inhibited MTT reduction and neurite outgrowth after 4 and 24 hours exposure at sub-lethal concentrations (0.1 and 1 µM). The inhibition of neurite outgrowth by sub-lethal concentrations of MeHgCl and thimerosal was accompanied by cytoskeletal changes in the cells. At 4 hours in C6 cells there was no change in the levels of tyrosinated a-tubulin, whereas in N2a cells the level of tubulin tyrosination was shown to be reduced compared to the control. Both cell lines exhibited a fall in total a-tubulin, tyrosinated a-tubulin and total ß-tubulin after 24 hours of exposure to organic mercury compounds, indicating proteolysis and/or reduced synthesis of the tubulin subunit. N2a cells also showed a decrease in the levels of phosphorylation in the neurofilament heavy chain after 4 hours of exposure to thimerosal and MeHgCl, whereas after 24 hours there appeared to be proteolytic degradation, as the total neurofilament heavy chain levels were reduced compared to the untreated controls. Reduced levels of tubulin and NFH were confirmed by immunofluorescence staining of fixed cell monolayers. Western blotting analysis also indicated increased ERK activation in glial cells incubated with 0.1 and 1 µM thimerosal for 4 hours, followed by reduced activation after 24 hours exposure, whereas exposure to MeHgCl decreased the levels of ERK activation at both time points. In the neuronal cell line ERK activation was suppressed at both 4 and 24 hours and with both concentrations of the organic mercury compounds. As ERK activation plays a key role in the regulation of neurite outgrowth and NFH phosphorylation, both of which were inhibited by the addition of thimerosal and MeHgCl, the findings are consistent with a role for disrupted ERK signalling in the sub-lethal toxicity of these compounds. Both thimerosal and MeHgCl caused redistribution of SERCA and ryanodine receptors, both of which are mechanisms by which intracellular Ca2+ concentrations are maintained. As the endoplasmic reticulum (ER) houses both SERCA and ryanodine receptors, the reorganisation may indicate that organic mercury compounds cause redistribution of the ER. Such disruption may lead to sustained increases in intracellular Ca2+, causing elevated activity in Ca2+ dependant enzymes. Indeed, western blotting analysis and enzyme assays showed that calpain activity (particularly calpain 1) increased in response to sub-lethal concentrations of the organic mercury compounds. As calpains target cytoskeletal proteins, the increased activity may be at least partly responsible for reduced levels of tubulin and NFH.

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47

Coulibaly, Aminata P. "Changes in Sympathetic Preganglionic Neurons and Associated Glial Cells following Injury." Miami University / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=miami1281032308.

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48

Eduafo, Augusta K. "Mechanisms of Hyperglycemia-Induced ROS Production in Osmotically Swollen Glial Cells." Wright State University / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=wright1433185840.

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49

Mouzannar, Raymond. "Higher order chromatin degradation induced by hydrogen peroxide in glial cells." Morgantown, W. Va. : [West Virginia University Libraries], 2001. https://etd.wvu.edu/etd/controller.jsp?moduleName=documentdata&jsp%5FetdId=2098.

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Thesis (Ph. D.)--West Virginia University, 2001.
Title from document title page. Document formatted into pages; contains viii, 84 p. : ill. Includes abstract. Includes bibliographical references (p. 58-84).

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Donohue, Carolyn Elizabeth. "EXPRESSION OF Npcl IN GLIAL CELLS CORRECTS STERILITY IN Npcl-/- MICE." Thesis, The University of Arizona, 2009. http://hdl.handle.net/10150/192331.

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Dissertations / Theses on the topic 'Glial cells'

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