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1
Hiltscher, Juliane. "Glutamattransporter und genetisch bedingte Ataxien. Mutationssuche im EAAT1- und EAAT4-Gen." Lübeck Zentrale Hochschulbibliothek Lübeck, 2010. http://d-nb.info/1000297667/34.
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Hiltscher, Juliane [Verfasser]. "Glutamattransporter und genetisch bedingte Ataxien : Mutationssuche im EAAT1- und EAAT4-Gen / Juliane Hiltscher." Lübeck : Zentrale Hochschulbibliothek Lübeck, 2010. http://d-nb.info/1000297667/34.
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Agarwal, Shailesh Ramjilal. "Pharmacological modeling and regulation of excitatory amino acid transporters (EAATS)." CONNECT TO THIS TITLE ONLINE, 2007. http://etd.lib.umt.edu/theses/available/etd-09262007-111510/.
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Fromm, Andrea. "Mutationsscreening und alternative Spleißvarianten des Glutamattransporters EAAT2 bei amyotropher Lateralsklerose." [S.l. : s.n.], 2008. http://nbn-resolving.de/urn:nbn:de:bsz:289-vts-66108.
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Felbecker, Ansgar. "Neue 5'-Isoformen des Glutamattransporters EAAT2: RNA-Sequenzen und genomische Organisation." [S.l.] : Universität Ulm , Medizinische Fakultät, 2002. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB10913301.
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Köchert, Karl. "Development of a method to assess EAAT1 transcription levels in Alzheimer's disease." Master's thesis, Universität Potsdam, 2007. http://opus.kobv.de/ubp/volltexte/2008/1596/.
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Zur Zeit leiden ca. 24 Millionen Menschen auf der ganzen Welt unter Demenz, Alzheimer macht dabei 50-60% aller Demenzfälle aus. Da der Anteil der Bevölkerung, der an Demenz leidet, proportional zum Alter zunimmt und der Anteil älterer Menschen in der Gesellschaft von Jahr zu Jahr steigt, wird Alzheimer immer mehr zu einem ernstzunehmenden, gesellschaftlichen Problem.
Zum Stand der heutigen Forschung ist es etabliert, dass die Aminosäure Glutamat - quantitativ einer der wichtigsten Neurotransmitter im Zentralen Nervensystem (ZNS) - toxische Konzentrationen erreichen kann wenn sie - im Zuge der Übertragung von Aktionspotentialen - nach ihrer Freisetzung nicht aus dem Synaptischen Spalt entfernt wird. Viele Studien haben gezeigt, dass in der Alzheimerschen Krankheit die Glutamataufnahme beeinträchtigt ist, was zu toxischen Konzentrationen von Glutamat und dem daraus folgenden Absterben von Neuronen führt.
Der exitatorische Aminosäuretransporter 1 (EAAT1) gehört zu der Familie der Na+-abhängigen Glutamattransporter und stellt nach EAAT2 den quantitativ wichtigsten Glutamattransporter im ZNS dar. In diesem Projekt wurde eine bis dahin für den Menschen nicht bekannte EAAT1 Spleißvariante, in der Exon 3 ausgeschnitten wird, nachgewiesen. Diese Variante wurde EAAT1Δ3 genannt und stellt damit mit EAAT1Δ9 die zweite für EAAT1 nachgewiesene Spleißvariante dar. Eine auf real-time RT-PCR basierende Methode wurde entwickelt, um die Transkripte von EAAT1 wildtyp (EAAT1 wt), EAAT1Δ3 und EAAT1Δ9 zu quantifizieren. Proben aus verschiedenen Hirnarealen wurden aus einem Set von Kontrollen und Alzheimerfällen bei der Quantifizierung verwendet. Die gewählten Areale sind von der Alzheimerschen Krankheit unterschiedlich stark betroffen. Dies diente als interne Kontrolle für die durchgeführten Experimente und ermöglichte so die Differenzierung zwischen beobachteten Effekten: Nur Effekte die alleinig in von Alzheimer betroffenen Gehirnarealen auftreten, können als spezifisch für die Krankheit angesehen werden.
Die Resultate diese Projektes zeigen, dass EAAT1Δ3 in sehr geringer Anzahl transkribiert wird, die nur 0.15% der EAAT1 wt Transkription entspricht. Dahingegen entspricht das EAAT1 Δ9 Transkript im Durchschnitt 26.6% des EAAT1 wt Transkripts. Es wurde nachgewiesen, dass die Transkriptionsrate aller EAAT1 Varianten in Alzheimerfällen signifikant reduziert ist (P<0.0001). Dies
unterstützt die Theorie, dass bei Alzheimerfällen die EAAT1 Proteinexpression stark reduziert und der Glutamattransport, der normalerweise durch diesen Transporter gewährleistet wird, stark eingeschränkt ist. Dies wiederum resultiert in toxisch hohen Glutamatkonzentrationen und damit dem Absterben von Neuronen. Die gefundene Reduktion der EAAT1Transkription ist nicht spezifisch für Gehirnareale die von Alzheimer betroffen sind, sondern tritt in selbem Maße in nicht von Alzheimer betroffenen Gehirnarealen auf. Daraus lässt sich schließen, dass die Reduktion der EAAT1 Transkription eher ein Resultat eines in der Alzheimerschen Krankheit präsenten, grundlegenden Krankheitsmechanismus ist als deren Ursache.<br>Today about 24 Million people worldwide suffer from dementia, Alzheimer’s Disease accounts for approximately 50-60% of all dementia cases. As the prevalence of dementia grows with increasing age Alzheimer’s Disease becomes more and more of an issue for society as the proportion of elderly
people increases from year to year. It is well established, that the amino acid glutamate - quantitatively being the most important neurotransmitter
in the central nervous system (CNS) - may reach toxic concentrations if not cleared from the synaptic cleft into which it is released during transmittance of action potentials. In Alzheimer’s Disease there is strong evidence for a generally impaired glutamate uptake system which in turn is thought to result in toxic levels of the amino acid with the potential to kill off neurons. The excitatory amino acid transporter 1 (EAAT1) belongs to the family of Na+-dependent glutamate transporter and accounts together with EAAT2 for most of the glutamate uptake in the CNS. In this project a new splice variant of EAAT1, skipping exon 3 was detected in human brain samples and subsequently called EAAT1Δ3, this being the second splice variant found after the recent detection
of EAAT1Δ9. A method was developed to quantify the transcript of EAAT1 wt, EAAT1Δ3 and EAAT1Δ9 by means of real-time PCR. Samples were taken from different brain areas of a set of control and AD cases. The areas chosen for examination are affected differently in Alzheimer’s Disease, this was used an internal control for the experiments done in this project as to determine whether any effect observed is specific for AD, i.e. AD affected areas or is generally seen in all areas examined.
The results of this project show that EAAT1Δ3 is transcribed in very low copy numbers making up a proportion of 0.15% of EAAT1 wt whereas EAAT1Δ9 is transcribed in a considerably large proportion of EAAT1 wt of 26.6%.
It was moreover found that all EAAT1 variants are transcribed at significantly lower rates (P<0.0001) in AD cases, supporting the theory that EAAT1 protein expression is reduced to a point where glutamate uptake normally mediated by this transporter is impaired. This in turn is thought to result in toxic levels glutamate accounting for neuronal loss in the disease. No area-dependent effects were found, suggesting that the reduction of EAAT1 transcription is rather a result of an underlying general mechanism present in AD. Further research will have to be done to assess the degree of EAAT1 expression in AD and whether
those future findings match with the result of this project.
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Pantazis, Konstantinos. "Enterprise Architecture at the Financial Sector with the EAAT Tool." Thesis, KTH, Industriella informations- och styrsystem, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-138610.
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In this Master Thesis an Enterprise Architecture Decision Making analysis is proposed within the field of Enterprise Architecture. A case study at a company within the financial sector has been conducted for validation of the proposed analysis. Firstly, the Enterprise Architecture Analysis Tool (EAAT), which has been developed by the Industrial Information and Control Systems (ICS) department of KTH, is described. This tool has been used during the whole Case Study in order to create present and possible future state models for measuring Service Availability. These models, which are based on a Metamodel, make possible the analysis of the Service Availability. Finally, some future research suggestions in the context of decision-making in Enterprise Architecture with EAAT are given.
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Seefried, Ulrich [Verfasser]. "Alternatives RNA-Spleißen des Glutamattransporters EAAT2 im ZNS der Maus / Ulrich Seefried." Ulm : Universität Ulm. Medizinische Fakultät, 2001. http://d-nb.info/1015324916/34.
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Felbecker, Ansgar [Verfasser]. "Neue 5´-Isoformen des Glutamattransporters EAAT2: RNA-Sequenzen und genomische Organisation / Ansgar Felbecker." Ulm : Universität Ulm. Medizinische Fakultät, 2003. http://d-nb.info/1015438318/34.
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Tian, Guilian. "The molecular mechanism of loss of glial glutamate transporter EAAT2 in neurodegenerative disease." The Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=osu1187038549.
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Tian, Guilian. "The molecular mechanisms of the loss of glial glutamate transporter EAAT2 in neurodegenerative diseases." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1187038549.
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Leinenweber, Ariane [Verfasser]. "Regulation of Excitatory Amino Acid Transporter 2 (EAAT2) by Carboxy-terminal Domains / Ariane Leinenweber." Hannover : Bibliothek der Tierärztlichen Hochschule Hannover, 2010. http://d-nb.info/100962427X/34.
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Mullen, Gary. "Integrating Equine-Assisted Activities and Therapy (EAAT) into a Higher Learning Institution." ScholarWorks, 2010. https://scholarworks.waldenu.edu/dissertations/845.
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Collegiate equestrian programs are costly to operate, and cost often exceeds revenue from tuition. The local problem in this project study was the need for supplemental revenue to support a cost-intensive equestrian program, without cutbacks or raising student fees. The study examined the integration of an equine-assisted activities and therapy (EAAT) program for additional income, while capitalizing on existing institutional resources at a Midwestern university in the United States. Research questions explored how to implement an EAAT program to close the budgetary gap at the project site. Systems theory formed the conceptual framework for analyzing the relationship between program characteristics and budgetary adequacy, as well as promising points of intervention in the systemic relationship between program and budget. A mixed methods design included a quantitative survey of all U.S. post-secondary institutions (37) with EAAT programs. Survey data were expanded and validated through open-ended interviews using a panel of five experts selected from the survey group. Data analysis included the constant comparative method, member checking, and triangulation procedures. Focus groups provided feedback on analyzed data regarding application to the project site. Results revealed dominant themes: collaborations; the relationship with administration; finances; staffing; scheduling; and employability. A three-option proposal was created to integrate EAAT, which included students providing community EAAT services to enhance their professional skills, and program revenue. Beyond addressing the financial issue, the social change implications of this study include preparing college graduates for service-based careers that advance a culture of equity and diversity in the workplaces to which they will bring the values learned in the EAAT program.
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Mavencamp, Terri Lynn. "Design, Synthesis and Biological Evaluation of a Family of Excitatory Amino Acid Transporter 3 (EAAT3) Preferring Inhibitors." The University of Montana, 2009. http://etd.lib.umt.edu/theses/available/etd-03212009-152926/.
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<p>This work describes the synthesis and initial characterization of the biological activity of a family of EAAT3 preferring inhibitors, L-β-benzyl aspartate (L-β-BA) and L-β-BA derivatives. L-β-BA and derivatives were initially synthesized in an approximate 2:1 ratio of diasteromers (threo:erythro), using base promoted enolate addition. Kinetic analysis of 3H-D-aspartate uptake into C17.2 cells expressing the hEAATs demonstrated that L-threo-β-BA is the more potent diastereomer (Ki values of 9 µM for EAAT1, 10.0 µM for EAAT2 and 0.8 µM for EAAT3), acts competitively, and exhibits a 10-fold preference for EAAT3 compared to EAAT1 and EAAT2. Electrophysiological recordings of EAAT-mediated currents in Xenopus oocytes further identified L-β-BA as a non-substrate inhibitor. Derivatives of L-β-BA were prepared and characterized for the ability to inhibit 3H-D-aspartate uptake into hEAAT1-3 expressing C17.2 cells. Computational modeling and analysis of structure activity data suggest the area the aromatic moiety of L-β-BA derivatives probe is 1) 3-dimentionally confined, 2) more tolerant of substitutions at the 3 and 5 positions than the 4 position, 3) at least partially distinct from the area probed by L-TBOA and 4) more accessible in the EAAT3 protein than EAAT1 and EAAT2. Computational modeling supports the pharmacological data and lends insight into the selectivity observed with L-β-BA derivatives. Docking studies suggest that H-bonding interactions of L-β-BA derivatives with key residues in the binding site position L-β-BA analogues in a unique manner that is better tolerated in the EAAT3 protein than in the EAAT1 and EAAT2 proteins.</p>
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Mavencamp, Terri Lynn. "Design, synthesis and biological evaluation of a family of excitatory amino acid transporter 3 (EAAT3) preferring inhibitors." [Missoula, Mont.] : The University of Montana, 2008. http://etd.lib.umt.edu/theses/available/etd-03212009-152926/unrestricted/Mavencamp_umt_0136D_10009.pdf.
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Hotzy, Linda Sabrina Jasmin [Verfasser]. "Fluorometric approaches to analyze the structure-function relationship of excitatory amino acid transporters (EAATs) / Linda Sabrina Jasmin Hotzy." Hannover : Technische Informationsbibliothek und Universitätsbibliothek Hannover (TIB), 2013. http://d-nb.info/1032720204/34.
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Cao, Jin. "OPERATING SYSTEM SECURITYMODELING : An Experimental Study on the CySeMoL model." Thesis, KTH, Industriella informations- och styrsystem, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-176854.
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In this Master Thesis, several common applications and Windows operating systemservices are modeled within the field of information security. This thesis focuses onapplying the Enterprise Architecture Analysis Tool (EAAT) and the Cyber SecurityModeling Language (CySeMoL), which are developed by the Department of IndustrialInformation and Control System (ICS) at KTH. The overall objective of this study is todetermine the probability of the CySeMol model with a particular kind of attack. Theproject models six common applications on Windows platform and two Windowsoperating system services. The detailed information regarding the applications and defensemechanism are acquired from various sources. A few experiments have been carried out tovalidate the correctness of the predicted probabilities calculated by the CySeMoL. Theresults of the analysis suggest that the CySeMoL model has a good performance onoperating system vulnerability prediction. At last, some possible suggestions in the contextof the CySeMoL model are given.
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Maguire, Jamie Lynn. "The Impact of Glutamate Signaling on Tumor Progression." Diss., Neuroscience Program, George Washington University, 2004. http://hdl.handle.net/1961/121.
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Degree awarded (2004): PhDBmS, Neuroscience Program, George Washington University<br>Glutamate is critically important as an excitatory neurotransmitter in the central nervous system. Increasing evidence suggests additional signaling roles for glutamate in cell proliferation and migration in normal and oncogenic states. Recently, glutamate release from glioma cells has been shown to increase tumor growth in vivo. To investigate the mechanism of glutamate enhancement of tumor growth, we investigated the effect of glutamate on tumor cell proliferation, invasion, and glioma-induced cell death. Here we demonstrate that glutamate enhances tumor growth via increasing tumor cell proliferation and inducing excitotoxic death of cells surrounding the solid tumor mass, thereby facilitating tumor expansion. The evidence that glutamate enhances tumor growth suggests that regulating extracellular levels of glutamate may restrict tumor growth. In the normal brain, extracellular glutamate levels are maintained by a family of glutamate transporters. To investigate the therapeutic potential of regulating extracellular glutamate concentrations on tumor growth, we utilized a transgenic mouse model of EAAT2 glutamate transporter overexpression. In this report, we demonstrate that increased glutamate transport limits tumor growth in vivo and provides protection against glioma-associated neuronal cell death. In addition, seizure activity, often associated with the presence of a CNS tumor, is attenuated in transgenic mice overexpressing the glutamate transporter, EAAT2. These findings suggest that glutamate transporters may provide a new therapeutic target for limiting tumor expansion and secondary epileptogenesis.<br>Advisory Committee: Dr. Margaret Sutherland (Chair), Dr. Steven Patierno (Chair), Dr. Tim Hales, Dr. Vincent Chiappinelli, Dr. Linda Werling, Dr. Frances Noonan
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Rabbani, Talvia. "Empirical Testing of the CySeMoL Tool for Cyber Security Assessment – Case Study of Linux Server and MySQL." Thesis, KTH, Skolan för elektro- och systemteknik (EES), 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-187664.
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In this Master Thesis, several common applications used with MySQL and Linux server are modelled using the Enterprise Architecture Analysis Tool (EAAT) and the Cyber Security Modelling Language (CySeMoL), both developed by the Department of Industrial Information and Control System (ICS) at KTH. The objective of this study is to use the CySeMoL tool to evaluate the feasibility and correctness of the tool by simulating some particular type of attacks on a real life Linux server. A few common applications with MySQL on a Linux server and two Linux operating system services are modelled and explained together with their detailed information and defense mechanisms. A real life penetration test has then been carried out in order to validate the simulated results from the tool. The results of the analysis suggest that the security vulnerability predictions done by CySeMoL on a Linux server has good predictive performance.<br>I denna Masteruppsats modelleras ett antal vanliga applikationer på en MySQL- och Linuxplattform med hjälp av Enterprise Architecture Analysis Tool (EAAT) tillsammans med Cybersecurity Modeling Language (CySeMoL). Båda dessa är utvecklade vid avdelningen för industriella informations- och styrsystem (ICS) på KTH. Syftet med denna studie är att validera korrektheten av CySeMoL-verktygets sårbarhetsprediktioner genom att simulera ett antal specifika cyberattacker mot en Linuxplattform. Ett antal vanligt förekommande applikationer på en MySQL-plattform samt två operativsystemstjänster i en Linuxserver modelleras. Penetrationstest utförs därefter för att validera resultaten som simuleras i CySeMoL-verktyget. Studien visar att CySeMols förutsägelser stämmer väl med resultaten av penetrationstesterna.
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Mekki, Sofiane. "Synthèse de nouveaux dérivés de l'acide β-hydroxyaspartique β-Substitués : inhibiteurs du transport du glutamate dans le Système Nerveux Central (SNC)". Thesis, Montpellier 2, 2012. http://www.theses.fr/2012MON20079/document.
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Nos travaux ont porté sur la mise au point de synthèse de nouveaux dérivés β-substitués β-hydroxy aspartates : Inhibiteurs du transport du glutamate dans le système nerveux centrale (SNC). Ces analogues d'aspartates ont été caractérisés par différentes méthodes spectroscopiques (RMN-1H, RMN-13C et HRMS) et leur pureté énantiomérique a été confirmée par analyses HPLC chirale et des mesures de pouvoir rotatoire. Ce manuscrit est organisé en trois chapitres : la première partie présente un point bibliographique sur le système glutamatergique dans le SNC, en rappelant les différents récepteurs et transporteurs du glutamate dans ce système ainsi leurs agonistes et antagonistes spécifiques.Puis, nous avons décrit un aperçu sur les différentes synthèses de dérivés aspartates β-substitués et leurs activités inhibitrices vers les transporteurs du Glu dans le SNC.Afin d'avoir une grande diversité dans la structure les dérivés β-substitués β-hydroxy aspartates et réduire le temps de préparation et le nombre d'étapes de synthèse, nous avons développé dans la troisième partie de ce manuscrit deux stratégies originales et récentes pour préparer des dérivés -substitués -hydroxy aspartates via une aminohydroxylation asymétrique de Sharpless, qui est considérée comme l'étape clé dans cette synthèse.Enfin, Les résultats préliminaires de tests biologiques sur les dérivés β-substitués β-hydroxy aspartates protégés montrent que ces composés ne présentent aucune toxicité vers les cellules nerveuses de l'hippocampe de rat. L'étude de la cytotoxicité et l'activité inhibitrice de dérivés β-substitués β-hydroxy aspartates totalement déprotégés vis à vis du transport du glutamate dans le SNC sont actuellement en cours<br>Our work focused on the development of synthesis of originals β-substituted β-hydroxy aspartates derivatives: Inhibitors of glutamate transport in the central nervous system (CNS).These analogs of aspartate have been characterized by various spectroscopic methods (1H-NMR, 13C-NMR and HRMS) and their enantiomeric purity was confirmed by chiral HPLC analysis and D measurement.This manuscript is organized into three chapters: the first part presents a bibliographical point of the glutamatergic system in CNS, recalling the different receptors and glutamate transporters in this system and their specific agonists and antagonists.Then, we described an overview of the various syntheses of β-substituted aspartates derivatives and their inhibitory activities toward glutamate transporters in CNS.In order, to have a great diversity in the structure of β-substituted β-hydroxy aspartates derivatives and reduce preparation time and the number of synthetic steps, we have developed in the third part of this manuscript two recent and original strategies for prepare β-substituted β-hydroxy aspartates derivatives via asymmetric aminohydroxylation Sharpless, who is considered the key step in this synthesis. Finally, preliminary results of biological tests on optically pure aspartates derivatives showed no toxicity to nerve cells of the rat hippocampus. The study of the inhibitory activity of these derivatives towards transport of glutamate in CNS is currently underway
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Sirko, Alexandre. "Enterprise Application Modularity : New Features Related to Visualization and Measurement of Modulatity Within the Enterprise Architecture Analysis Tool (EAAT)." Thesis, KTH, Industriella informations- och styrsystem, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-141328.
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During my studies at the Ecole des Mines d'Albi-Carmaux, I did an internship at the Royal Institute of Technology (Kungliga Tekniska Högskolan) in Sweden to finalize my master. The subject of this exercise is positioned as the junction of two different research areas. There is on one hand the development of new analysis method of Enterprise Architecture (EA) and on the other the analysis of software architecture modularity. The entire mission concerns a method of analyzing the modularity of EA developed by Harvard Business School. The analysis method called "Hidden Structure" aims to evaluate the components of software and isolate vulnerable or key components. This internship's main task is to develop the Enterprise Application Modularity module. It is a module dedicated to the modularity analysis according to the hidden structure method and its integration with the Enterprise Architecture Analysis Tool (EAAT) software developed by KTH. This project also needs to develop additional functionalities to support the calculations. Among these features, you can find support for instantiation of new models and automated generation of reports containing the results.
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Brothers, Holly M. "Neuroinflammation, Glutamate Regulation and Memory." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1363603410.
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Frost, Per. "Utvärdering av den upplevda användbarheten hos CySeMoL och EAAT med hjälp av ramverk för ändamålet och ISO/IEC 25010:2011." Thesis, KTH, Industriella informations- och styrsystem, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-138576.
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This report describes a study aimed at uncovering flaws and finding potential improvements from when the modelling tool EAAT is used in conjunction with the modelling language CySeMoL. The study was performed by developing a framework and applying it on CySeMoL and EAAT in real life context networks. The framework was developed in order to increase the number of flaws uncovered as well as gather potential improvements to both EAAT and CySeMoL. The basis of the framework is a modified version of the Quality in use model from ISO/IEC 25010:2011 standard. Upon the characteristics and sub characteristics of this modified model different values for measuring usability where attached. The purpose of these values is to measure usability from the perspectives of both creating and interpreting models. Furthermore these values are based on several different sources on how to measure usability. The complete contents of the framework and the underlying ideas, upon which the framework is based, are presented in this report. The framework in this study was designed in order to enable it to be used universally with any modelling language in conjunction with a modelling tool. Its design is also not limited to the field of computer security and computer networks, although that is the intended context of CySeMoL as well as the context described in this report. However, utilization outside the intended area of usage will most likely require some modifications, in order to work in a fully satisfying. Several flaws where uncovered regarding the usability of CySeMoL and EAAT, but this is also accompanied by several recommendations on how to improve both CySeMoL and EAAT. Because of the outline of the framework, the most severe flaws have been identified and recommendations on how to rectify these shortcomings have been suggested.
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Dalet, Antoine. "Homéostasie glutamatergique des synapses en calice de l’appareil vestibulaire : implication de plusieurs transporteurs du glutamate de la famille des EAAT." Thesis, Montpellier 2, 2011. http://www.theses.fr/2011MON20115/document.
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L'homéostasie glutamatergique dans les fentes synaptiques régule la neurotransmission et préserve de l'excitotoxicité. Cela est particulièrement important dans l'oreille interne où il y a une libération soutenue de neurotransmetteur. Pour la plupart des cellules ciliées cochléaires et vestibulaires, la clairance du glutamate est assurée par les transporteurs du glutamate EAAT1 (GLAST) exprimés par les cellules de soutien. Un tel mécanisme n'est pas possible pour les cellules ciliées vestibulaires de type I car leur terminaison synaptique en calice empêche tout accès à la fente synaptique. Nous avons donc postulé qu'un ou plusieurs transporteurs du glutamate devaient être présents au niveau des cellules ciliées de type I ou du calice ou des deux.Grâce à des enregistrements électrophysiologiques, nous avons démontré qu'un courant anionique induit par le glutamate et bloqué par le DL-TBOA est présent dans les cellules ciliées de type I. Les techniques d'hybridation in situ et d'immunohistochimie ont révélé la présence d'EAAT4 et EAAT5. Ces deux transporteurs du glutamate, qui pourraient êtres à l'origine des courants enregistrés, sont exprimés par les cellules ciliées de type I et de type II. De plus, des expériences de RT-PCR et de microscopie électronique ont confirmé ces résultats et suggéré que ces transporteurs pourraient aussi être exprimés postsynaptiquement par le calice. Ces travaux de thèse montrent qu'EAAT4 et EAAT5, considérés respectivement comme spécifiques des tissus cérébelleux et rétiniens, ont une distribution plus large. Ces résultats posent la question des rôles potentiels de ces transporteurs dans l'homéostasie glutamatergique vestibulaire<br>Glutamate homeostasis in synaptic clefts shape neurotransmission and prevent excitotoxicity. This may be particularly important in the inner ear where there is a continually high rate of neurotransmitter release. In the case of most cochlear and vestibular hair cells, clearance involves the diffusion of glutamate to supporting cells, where it is taken up by EAAT1 (GLAST), a glial glutamate transporter. A similar mechanism is unlikely to work in vestibular type I hair cells because the presence of calyx endings separates supporting cells from the synaptic zone. Based on this arrangement, we postulated that a glutamate transporter must be present in the type I hair cell, the calyx ending, or both. Using whole-cell patch-clamp recordings, we demonstrated that a glutamate-activated anion current blocked by DL-TBOA is expressed in type I hair cells. In situ hybridization and immunohistochemistry revealed that EAAT4 and EAAT5, two glutamate transporters that could support the anion current, are expressed in both type I and type II hair cells. Furthermore, RT-PCR and immunogold investigations confirmed those results and added that although preferentially expressed presynaptically, the transporters may also be present in the postsynaptic calyx membrane. Previously thought to be exclusively expressed in the cerebellum and retina respectively, this thesis work shows that EAAT4 and EAAT5 have a wider distribution. The potential role of these transporters in the glutamatergic homeostasis of the calyx synapse is then discussed
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Westerberg, Per. "Enterprise Architecture Analysis : - Astudy of the IT landscape atAstraZeneca." Thesis, KTH, Industriella informations- och styrsystem, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-169227.
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A case study at a global pharmaceutical company has been conducted toanalyse how the Hidden Structure method using the Enterprise Architecture Analyses(EAAT) tool, developed at KTH, can be used to visualize the IT architecture and tocreate a better understanding on which applications could increase a risk of therobustness of the architecture if changes was done to them. Also the measure of ITsupport metrics as incidents and changes per system has been analysed to understandif they can be used to understand the robustness of the incident. The tool was used tocreate a model of the enterprise architecture of the company and the analysis showedthat the robustness of the IT architecture was good; the core applications that couldcreate most damage were identified. The analysis of the IT support metrics showedthat it was difficult to use the change records as indicators since the number ofchanges per systems were very few. The incident analysis showed that the systemswith the highest number of incidents were classified as belonging core or peripheralcategory.
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Sreemantula, Sai Nandini. "Glutamate Transporter 1 in the Central Nervous System: Potential Target for the Treatment of Alcohol Dependence." University of Toledo Health Science Campus / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=mco1333546775.
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Roman, Kenny M. "GLT-1 over-expression attenuates visceral nociception by pharmacological and gene therapy approaches." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1332424243.
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Rosell, Peter. "Enterprise Architecture Modeling of Core Administrative Systems at KTH : A Modifiability Analysis." Thesis, KTH, Industriella informations- och styrsystem, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-99166.
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This project presents a case study of modifiability analysis on the Information Systems which are central to the core business processes of Royal Institution of Technology in Stockholm, Sweden by creating, updating and using models. The case study was limited to modifiability regarding only specified Information Systems. The method selected was Enterprise Architecture together with Enterprise Architecture Analysis research results and tools from the Industrial Information and Control Systems department of the same University. Jointly used with the ArchiMate modelling language, to create the models and perform the analysis. The results demonstrated to be very varied in regards to system models and modifiability. The Alumni Commu-nity system seemed to have very high modifiability whereas the Ladok på Webben system seemed to have the low modifiability, and other systems ranging differently or in between. The case study results found three slightly more critical systems of all the systems analysed: Ladok på Webben, Nya Antagningen & La-dok Nouveau. The first two showed to have either very low or low modifiability while being highly coupled to the other systems. Therefore any modification to these two systems would most likely cause effects that would require change in interconnected systems. Whereas Ladok Nouveau, while having average modifia-bility, has a critical position to process activities, is nearly isolated from all other systems, making them indi-rectly dependent on the system through the interconnected LADOK database. The study showed that the systems developed at KTH are comparable with systems developed by commercial enterprises in terms of modifiability. The study also provided insight into an Enterprise Architecture where the systems have dif-ferent development origins and how this could affect modifiability and analysis.
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Foster, Joshua B. "Development of Pyridazine-Derivatives for the Treatment of Neurological Disorders." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1545904228813231.
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Johansson, Dan. "Empirical test of a tool for cyber security vulnerability assessment." Thesis, KTH, Skolan för datavetenskap och kommunikation (CSC), 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-176032.
Full textAbstract:
This report describes a study aimed at verifying a cyber security modeling language named the Predictive, Probabilistic Cyber Security Modelling Language. This modeling language together with the Enterprise Architecture Analysis Tool acts as a tool for cyber security evaluations of system architectures. To verify the accuracy and readiness of the tool, a generic model of a real life Supervisory Control And Data Acquisition System’s system architecture was modeled using the tool and later evaluated. The evaluation process consisted of a Turing test, which was the same method used for evaluation of the Predictive, Probabilistic Cyber Security Modelling Language predecessor the Cyber Security Modelling Language. For the Turing test, interviews were held with five domain experts within cyber security. Four of which were tasked with creating attack paths given a scenario in the modeled system architecture. The Predictive, Probabilistic Cyber Security Modelling Language was given the same task as the four experts. The attack paths created were consolidated in a standardized form for the last internal company expert within cyber security to evaluate. An expert evaluator was tasked with grading the attack paths produced by the four experts and the Predictive, Probabilistic Cyber Security Modelling Language. The grading was based on how probable the attack paths were perceived by the internal expert. The conclusion was made that given the limitations of the study, the Predictive, Probabilistic Cyber Security Modelling Language produced a cyber security evaluation that was as probable as those created by the human cyber security experts. The results produced were also consistent with the results produced by the Predictive, Probabilistic Cyber Security Modelling Language predecessor the Cyber Security Modelling Language in a previous study. Suggestions for further studies were also introduced which could complement this study and further strengthen the results. This thesis was a collaboration between ABB Enterprise Software and the members of the team behind the Predictive, Probabilistic Cyber Security Modelling Language at ICS at KTH.<br>Denna rapport beskriver en studie vars mål var att verifiera ett modelleringsspråk för datasäkerhet vid namn Predictive, Probabilistic Cyber Security Modelling Language. Detta modelleringsspråk tillsammans med Enterprise Architecture Analysis Tool utgör ett verktyg för datasäkerhetsutvärderingar av systemarkitekturer. För att verifiera exaktheten och mognadsnivån på verktyget så skapades en generisk modell av ett verkligt Supervisory Control And Data Acquisition System-systems arkitektur. Denna modell utvärderades i ett senare skede. Utvärderingsprocessen bestod av ett Turingtest, som är samma metod som användes i en tidigare utvärdering av Predictive, Probabilistic Cyber Security Modelling Languages föregångare Cyber Security Modelling Language. För Turingtestet hölls fem intervjuer med domänexperter inom datasäkerhet. Fyra av dessa fick i uppgift att skapa attackvägar givet ett scenario i den modellerade systemarkitekturen. Attackvägarna som skapades sammanställdes i ett standardiserat formulär för den sista interna företagsexperten inom datasäkerhet att utvärdera. En expertutvärderare fick i uppgift att betygsätta de attackvägar som hade producerats av de fyra experterna och Predictive, Probabilistic Cyber Security Modelling Language. Betygsättningen baserades på hur sannolika de olika attackvägarna uppfattades av den interna experten. Slutsatsen som gjordes var att givet begränsningarna i studien, så producerade Predictive, Probabilistic Cyber Security Modelling Language en datasäkerhetsutvärdering som var likvärdigt sannolik jämfört med de som skapades av mänskliga experter. Resultaten som producerades var också konsistenta med resultaten som producerades av Predictive, Probabilistic Cyber Security Modelling Language föregångare Cyber Security Modelling Language i en tidigare studie. Förslag på kommande studier som skulle komplettera denna studie och stärka resultaten ytterligare introducerades också. Detta examensarbete var ett samarbete mellan ABB Enterprise Software och medlemmarna i teamet bakom Predictive, Probabilistic Cyber Security Modelling Language på ICS på KTH.
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Munger, Emily LaRee. "Alteration to Astrocyte Density and Morphology across Mammalia with Specific Attention to Primate Brain Evolution and Aging." Kent State University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=kent1594638449298271.
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Kim, Seol-Hee. "Acetaminophen Associated Neurotoxicity and its Relevance to Neurodevelopmental Disorders." Scholar Commons, 2017. http://scholarcommons.usf.edu/etd/6717.
Full textAbstract:
Autism is a lifelong neurodevelopmental disorder. The etiology of autism still remains unclear due to the heterogeneous and complex nature of the disorder, however synergistic actions between genetic components and environmental factors have been suggested. Acetaminophen (APAP) is one of the most popular over-the-counter drugs that possess antipyretic and analgesic effects. It is considered a relatively safe and effective within therapeutic doses. Recently, early exposure to APAP has been suggested to be one of the underlying cause of autism. Children are often prescribed APAP to lessen fever or irritability after vaccination during the first year, and APAP may adversely affect the normal brain development. In order to better understand the association with APAP and autism, we used an inbred mouse strain BTBR T+tf/J (BTBR). BTBR exhibits behavioral deficits that mimic the core behavioral deficits of human autism. In the study, investigated 1) if BTBR mice showed differences in thiol biochemistry and EAAT3 levels in brain compared with C57BL/6J (C57) mice, 2) if early exposure to APAP induced behavioral changes worsening the autistic phenotypes of BTBR in adolescence, and 3) if APAP exposure in neonatal mice induced possible toxicity at various doses. As a result, we observed that BTBR mice have significantly lower plasma sulfate levels and EAAT expression levels in the frontal cortex compared to C57 mice. Surprisingly, neonatal therapeutic dose of APAP administration did not induce behavioral changes in both C57 and BTBR in adolescence. However, we showed that a supratheraputic dose of APAP significantly elevated levels of oxidative stress marker in the brain. Overall, the results suggested that BTBR mice would be a useful mouse model to investigate effects of various environmental factors that have been associated with autism. In addition, early exposure to APAP at supratherapeutic doses may negatively affect normal brain development.
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Sopjani, Mentor [Verfasser]. "The AMP activated protein kinase in the regulation of sodium coupled transporters (SGLT1, EAAT3 & EAAT4) and eryptosis / von Mentor Sopjani." 2010. http://d-nb.info/100125581X/34.
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Melzer, Nico [Verfasser]. "Der Anionenkanal des neuronalen Glutamattransporters EAAT4 / vorgelegt von Nico Melzer." 2006. http://d-nb.info/98360004X/34.
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Schniepp, Roman [Verfasser]. "Regulation der exzitatorischen Aminosäure-Transporter EAAT1, EAAT2, EAAT3 und EAAT5 durch die Serum- und Glukokortikoid-abhängige Kinase SGK und die Ubiquitinligase Nedd4-2 / vorgelegt von Roman Schniepp." 2006. http://d-nb.info/98366790X/34.
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Weiss, Thorsten [Verfasser]. "Das Expressionsverhalten der glialen Glutamattransporter EAAT1 und EAAT2 sowie von PACAP nach Schädel-Hirntrauma des Menschen / von Thorsten Weiss." 2006. http://d-nb.info/981850995/34.
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Yi, Jae-Hyuk. "Les mécanismes excitotoxiques et le rôle de transporteurs de glutamate dans la physiopathologie des traumatismes crâniens = Excitotoxic mechanisms and the role of glutamate transporters in the pathophysiology of traumatic brain injury." Thèse, 2006. http://hdl.handle.net/1866/15364.
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Kim, Helena J. "Effects of long-term inhibition of EAAT2 on the excitability of spinal dorsal horn neurons." Master's thesis, 2010. http://hdl.handle.net/10048/1619.
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This thesis examined the effects of long-term inhibition of excitatory amino acid transporter 2 (EAAT2) on the excitability of dorsal horn neurons in defined-medium organotypic slice cultures (DMOTCs). Previous reports suggest that inhibition of EAAT2 may be involved in development of neuropathic pain induced by brain-derived neurotrophic factor (BDNF). Experiments were carried out using confocal Ca2+ imaging to assess the excitability of dorsal horn neurons.
Long-term treatment with EAAT2 blocker, dihydrokainate (DHK), prominently increased the neuronal excitability. Long-term exposure to DHK had a significant effect on NMDA, AMPA and metabotropic glutamate subtype 1 (mGluR1) receptors. Lastly, long-term treatment with BDNF and DHK increased activity of AMPA receptors but only DHK significantly increased activity of NMDA receptors. These findings suggest inhibition of EAAT2 and BDNF may have different pathways to promote neuropathic pain and modulating the activity of EAAT2 may be a novel therapeutic approach for neuropathic pain.
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Pannunzio, Marc. "Effets du cuivre (II) sur le transport à haute affinité du glutamate dans des astrocytes en culture : proposition d'un mécanisme physiopathologique de la maladie de Wilson." Thèse, 2003. http://hdl.handle.net/1866/14883.
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Fromm, Andrea Heike Lydia [Verfasser]. "Mutationsscreening und alternative Spleivarianten des Glutamattransporters EAAT2 bei amyotropher Lateralsklerose / vorgelegt von Andrea Heike Lydia Fromm." 2008. http://d-nb.info/100069450X/34.
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"Design, synthesis and biological evaluation of a family of excitatory amino acid transporter 3 (EAAT3) preferring inhibitors." UNIVERSITY OF MONTANA, 2009. http://pqdtopen.proquest.com/#viewpdf?dispub=3338786.
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Chawla, Aarti R. "CaMKII regulation of astrocytic glutamate uptake." Diss., 2016. http://hdl.handle.net/1805/10605.
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Indiana University-Purdue University Indianapolis (IUPUI)<br>Glutamate clearance by astrocytes is an essential part of physiological excitatory
neurotransmission. Failure to adapt or maintain low levels of glutamate in the central
nervous system is associated with multiple acute and chronic neurodegenerative diseases.
The primary excitatory amino acid transporters (EAATs) in human astrocytes are EAAT1
and EAAT2 (GLAST and GLT-1 respectively in rodents). While the inhibition of a
ubiquitously-expressed serine/threonine protein kinase, the calcium/calmodulindependent
kinase (CaMKII) results in diminished glutamate uptake in cultured primary
rodent astrocytes, the molecular mechanism underlying this regulation is unknown. In
order to delineate this mechanism, we use a heterologous expression model to explore
CaMKII regulation of EAAT1 and EAAT2. In transiently transfected HEK293T cells,
pharmacological inhibition of CaMKII and overexpression of a dominant-negative
version of CaMKII (Asp136Asn) reduces [3H]-glutamate uptake by EAAT1, without
altering EAAT2 mediated glutamate uptake. Surprisingly, overexpression of a
constitutively active autophosphorylation mutant (Thr287Asp) to increase autonomous
CaMKII activity and a mutant incapable of autophosphorylation (Thr287Val) had no
effect on either EAAT1 or EAAT2 mediated glutamate uptake. Pulldown of FLAGtagged
glutamate transporters suggests CaMKII does not interact with EAAT1 or
EAAT2. SPOTS peptide arrays and recombinant GST-fusion proteins of the intracellular
N- and C-termini of EAAT1 identified two potential phosphorylation sites at residues
Thr26 and Thr37 in the N-terminus. Introducing an Ala (a non-phospho mimetic) but not an Asp (phosphomimetic) at Thr37 diminished EAAT1-mediated glutamate uptake,
suggesting that the phosphorylation state of this residue is important for constitutive
EAAT1 function. In sum, this is the first report of a glutamate transporter being identified
as a direct CaMKII substrate. These findings indicate that CaMKII signaling is a critical
driver of homeostatic glutamate uptake by EAAT1. Aberrations in basal CaMKII activity
disrupt glutamate uptake, which can perpetuate glutamate-mediated excitotoxicity and
result in cellular death.
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Ugbode, Christopher I., W. D. Hirst, and Marcus Rattray. "Neuronal influences are necessary to produce mitochondrial co-localization with glutamate transporters in astrocytes." 2014. http://hdl.handle.net/10454/7811.
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yes<br>Abstract
Recent evidence suggests that the predominant astrocyte
glutamate transporter, GLT-1/ Excitatory Amino Acid Transporter
2 (EAAT2) is associated with mitochondria. We used
primary cultures of mouse astrocytes to assess co-localization
of GLT-1 with mitochondria, and tested whether the interaction
was dependent on neurons, actin polymerization or the kinesin
adaptor, TRAK2. Mouse primary astrocytes were transfected
with constructs expressing V5-tagged GLT-1, pDsRed1-Mito
with and without dominant negative TRAK2. Astrocytes were
visualized using confocal microscopy and co-localization was
quantified using Volocity software. Image analysis of confocal
z-stacks revealed no co-localization between mitochondria
and GLT-1 in pure astrocyte cultures. Co-culture of astrocytes
with primary mouse cortical neurons revealed more mitochondria
in processes and a positive correlation between mitochondria
and GLT-1. This co-localization was not further
enhanced after neuronal depolarization induced by 1 h treatment
with 15 mM K+. In pure astrocytes, a rho kinase inhibitor,
Y27632 caused the distribution of mitochondria to astrocyte
processes without enhancing GLT-1/mitochondrial co-localization,
however, in co-cultures, Y27632 abolished mitochondrial:
GLT-1 co-localization. Disrupting potential mitochondrial:
kinesin interactions using dominant negative TRAK2 did not
alter GLT-1 distribution or GLT-1: mitochondrial co-localization.
We conclude that the association between GLT-1 and
mitochondria is modest, is driven by synaptic activity and
dependent on polymerized actin filaments.
Mitochondria have limited co-localization with the glutamate transporter GLT-1 in primary astrocytes in culture. Few mitochondria are in the fine processes where GLT-1 is abundant. It is necessary to culture astrocytes with neurones to drive a significant level of co-localization, but co-localization is not further altered by depolarization, manipulating sodium ion gradients or Na/K ATPase activity.
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Ugbode, Christopher I., W. D. Hirst, and Marcus Rattray. "Astrocytes grown in Alvetex® 3 dimensional scaffolds retain a non-reactive phenotype." 2015. http://hdl.handle.net/10454/8062.
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yes<br>Protocols which permit the extraction of primary astrocytes from either embryonic or postnatal mice are well established however astrocytes in culture are different to those in the mature CNS. Three dimensional (3D) cultures, using a variety of scaffolds may enable better phenotypic properties to be developed in culture. We present data from embryonic (E15) and postnatal (P4) murine primary cortical astrocytes grown on coated coverslips or a 3D polystyrene scaffold, Alvetex. Growth of both embryonic and postnatal primary astrocytes in the 3D scaffold changed astrocyte morphology to a mature, protoplasmic phenotype. Embryonic-derived astrocytes in 3D expressed markers of mature astrocytes, namely the glutamate transporter GLT-1 with low levels of the chondroitin sulphate proteoglycans, NG2 and SMC3. Embroynic astrocytes derived in 3D show lower levels of markers of reactive astrocytes, namely GFAP and mRNA levels of LCN2, PTX3, Serpina3n and Cx43. Postnatal-derived astrocytes show few protein changes between 2D and 3D conditions. Our data shows that Alvetex is a suitable scaffold for growth of astrocytes, and with appropriate choice of cells allows the maintenance of astrocytes with the properties of mature cells and a non-reactive phenotype.<br>BBSRC
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Carbone, M., S. Duty, and Marcus Rattray. "Riluzole neuroprotection in a parkinson’s disease model involves suppression of reactive astrocytosis but not GLT-1 regulation." 2012. http://hdl.handle.net/10454/7807.
Full textAbstract:
yes<br>Background: Riluzole is a neuroprotective drug used in the treatment of motor neurone disease. Recent evidence
suggests that riluzole can up-regulate the expression and activity of the astrocyte glutamate transporter, GLT-1.
Given that regulation of glutamate transport is predicted to be neuroprotective in Parkinson’s disease, we tested
the effect of riluzole in parkinsonian rats which had received a unilateral 6-hydroxydopamine injection into the
median forebrain bundle.
Results: Rats were treated with intraperitoneal riluzole (4 mg/kg or 8 mg/kg), 1 hour before the lesion then once
daily for seven days. Riluzole produced a modest but significant attenuation of dopamine neurone degeneration,
assessed by suppression of amphetamine-induced rotations, preservation of tyrosine hydroxylase positive neuronal
cell bodies in the substantia nigra pars compacta and attenuation of striatal tyrosine hydroxylase protein loss.
Seven days after 6-hydroxydopamine lesion, reactive astrocytosis was observed in the striatum, as determined by
increases in expression of glial fibrillary acidic protein, however the glutamate transporter, GLT-1, which is also expressed in astrocytes was not regulated by the lesion.
Conclusions: The results confirm that riluzole is a neuroprotective agent in a rodent model of parkinson’s disease.
Riluzole administration did not regulate GLT-1 levels but significantly reduced GFAP levels, in the lesioned striatum.
Riluzole suppression of reactive astrocytosis is an intriguing finding which might contribute to the neuroprotective effects of this drug.
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Peng, Jhan-Jie, and 彭湛傑. "Investigate roles of Drosophila Eaat1-mediated glutamate clearance in the functional integrity of the motor circuit and the formation of the neuromuscular junction." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/02184445433768124130.
Full textAbstract:
碩士<br>國立臺灣大學<br>生化科學研究所<br>104<br>Glutamate transmission in CNS is critical for animal behavior. Upon the release of glutamate from synaptic vesicles, it is immediately removed by the surrounding astrocyte. The Excitatory Amino Acid Transporter (Eaat) in astrocyte is majorly responsible for the glutamate clearance in CNS, which ensures the fidelity of neurotransmission and prevents glutamate excitotoxicity. In neurodegenerative diseases, downregulation of Eaat has been repeatedly reported and accumulation of extracellular glutamate due to impaired recycle system accelerates the disease progression. Although how excessive glutamate leads to neuronal death has been widely studied, the influence of glutamate excitotoxicity on neural circuit is still elusive. Here, we use Drosophila larval locomotor circuit to study the role of glia on the glutamate transmission in CNS. From a genetic screen for novel players involved in synaptic formation, we identified a strong hypomorphic Drosophila eaat1 allele which led to strong loss of eaat1, expanded neuromuscular junction, and severe locomotor deficits. The locomotion of Drosophila larva is controlled by the neural circuit called central pattern generator (CPG). Loss of eaat1 resulted in aberrant CPG activity which caused prolonged but less frequent activation of motoneurons. Restoring the expression of eaat1 exclusively in the astrocyte was sufficient to restore the CPG and locomotion defects in eaat1 mutants. Impaired glutamate clearance in loss of eaat1 led to extracellular glutamate accumulation and disrupted the excitatory and inhibitory synaptic signaling in the CPG. Remarkably, reducing the oxidative stress or increasing the excitability of excitatory cholinergic neurons in eaat1 mutants improved both CPG rhythmicity and mobility. Moreover, the irregular CPG firing pattern in loss of eaat1 triggered the ROS/JNK signaling in motorneurons and caused excessive synaptic bouton formation. We demonstrated a non-cell autonomous mechanism to regulate the physiology of motoneurons via Eaat1 in upstream astrocyte.
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Winterberg, Markus [Verfasser]. "Der humane Transporter EAAT 3 ist ein Kandidat für die Vermittlung der L-Glutamat-Aufnahme in Plasmodium-falciparum-infizierte Erythrozyten / vorgelegt von Markus Winterberg." 2009. http://d-nb.info/99588112X/34.
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Carbone, M., S. Duty, and Marcus Rattray. "Riluzole elevates GLT-1 activity and levels in striatal astrocytes." 2012. http://hdl.handle.net/10454/5907.
Full textAbstract:
Drugs which upregulate astrocyte glutamate transport may be useful neuroprotective compounds by preventing excitotoxicity. We set up a new system to identify potential neuroprotective drugs which act through GLT-1. Primary mouse striatal astrocytes grown in the presence of the growth-factor supplement G5 express high levels of the functional glutamate transporter, GLT-1 (also known as EAAT2) as assessed by Western blotting and (3)H-glutamate uptake assay, and levels decline following growth factor withdrawal. The GLT-1 transcriptional enhancer dexamethasone (0.1 or 1 muM) was able to prevent loss of GLT-1 levels and activity following growth factor withdrawal. In contrast, ceftriaxone, a compound previously reported to enhance GLT-1 expression, failed to regulate GLT-1 in this system. The neuroprotective compound riluzole (100 muM) upregulated GLT-1 levels and activity, through a mechanism that was not dependent on blockade of voltage-sensitive ion channels, since zonasimide (1 mM) did not regulate GLT-1. Finally, CDP-choline (10 muM-1 mM), a compound which promotes association of GLT-1/EAAT2 with lipid rafts was unable to prevent GLT-1 loss under these conditions. This observation extends the known pharmacological actions of riluzole, and suggests that this compound may exert its neuroprotective effects through an astrocyte-dependent mechanism.