Dissertations / Theses on the topic 'Astrocytes'
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Contreras-Sesvold, Carmen Sesvold Carmen Contreras. "Reactive astrocytes : phenotypic and functional characteristics and astrocytes as neural stem cells /." Download the thesis in PDF, 2006. http://www.lrc.usuhs.mil/dissertations/pdf/ContrerasSesvold2006.pdf.
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Feresten, Abigail Helms. "Astrocytes in psychotic disorder." Thesis, University of British Columbia, 2013. http://hdl.handle.net/2429/45435.
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Astrocyte dysregulation has been implicated in the pathophysiology of schizophrenia (SCZ) and bipolar disorder (BPD), however the exact nature of astrocytic alterations remains to be identified. I investigated whether levels of four astrocyte-specific proteins; glial fibrillary acidic protein (GFAP), aldehyde dehydrogenase type 1L1 (ALDH1L1), vimentin, and excitatory amino acid transporter type 1 (EAAT1) are altered in SCZ and BPD. Immunohistochemical staining of ALDH1L1 and GFAP in human grey and white matter was also performed, and staining patterns compared qualitatively. Relative concentrations of GFAP, ALDH1L1, vimentin, and EAAT1 were assessed post-mortem in the dorsolateral prefrontal cortex in SCZ (n=35), BPD (n=34) and non-psychiatric control (n=35) groups by western blotting. The same proteins were also quantified in the cingulate cortex of rats administered the antipsychotics haloperidol and clozapine. Elevated levels of GFAP were observed in SCZ and BPD, when compared to controls. GFAP was also significantly increased in individuals with psychotic symptoms, when compared to those without. Vimentin, ALDH1L1 and EAAT1 levels did not differ between groups. Rats exposed to antipsychotics did not exhibit significant overall differences in any astrocytic protein, suggesting that increased GFAP in SCZ is not attributable to antipsychotic treatment. Our findings indicate that astrocyte pathology may be associated with psychotic symptoms. Lack of ALDH1L1 and vimentin variability, paired with increased GFAP levels, may imply that astrocyte numbers are unchanged but astrocytes are partially activated, or may indicate a specific dysregulation of GFAP. Immunohistochemical results suggest that ALDH1L1 may be a more reliable marker of astrocytes than GFAP in human grey matter.
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Jai-Yoon, Sul. "Calcium signalling in astrocytes." Thesis, King's College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391921.
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Škovierova, H., S. Mahmood, E. Blahovcova, J. Strnadel, J. Sopkova, and E. Halašova. "Homocystene and human astrocytes." Thesis, Сумський державний університет, 2016. http://essuir.sumdu.edu.ua/handle/123456789/44950.
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Astrocytes are multipotent and serve surprisingly large and diverse variety of functions, providing for the overall brain homeostasis, assisting in neurogenesis, determining the microarchitecture of the grey matter, and defending the brain through evolutionary conserved astrogliosis programs. Astrocytes are specifically involved in various neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases, and various forms of dementia. Homocysteine is a nonessential sulphur-containing amino acid that had been linked with neurodegenerative diseases and aging.
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James, L. R. "Calcium signal transduction in astrocytes." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.605022.
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Ca2+ signals can exhibit great spatiotemporal complexity, leading to the hypothesis that the dynamics of Ca2+ signals may allow astrocytes to discriminate between stimuli. An in vitro model system of primary cerebellar and cortical astrocytes was tailored to test this hypothesis, by comparing the kinetics of the Ca2+ signal evoked by different receptor agonists. It was found that known physiological agonists triggered highly heterogeneous responses, but there were no systematic trends in the specific kinetic parameters of Ca2+ signals that depended on the agonists which triggered them. These results suggest that the encoding of information as to agonist identity in the timing of the Ca2+ signal is unlikely to be feasible. However, different agonists vary in the efficacy with which they trigger cell-wide Ca2+ signals suggesting that there is a discrete probability that cultured astrocytes will respond to a given agonist with an all-or-none Ca2+ signal. The probability of triggering a response can be enhanced by the neuromodulator nitric oxide (NO), acting through its receptor, soluble guanylyl cyclase (sGC). The mechanism of this “gain modulation” involves activation of PKG and PKC modulating an aspect of the Gq signalling pathway in a manner that increases Ca2+ excitability. Further investigations revealed complex crosstalk between the NO and Ca2+ signalling pathways at multiple levels. In summary, the kinetics of Ca2+ signalling in cultured astrocytes while heterogeneous, do not appear to vary predictably between physiological stimuli. Instead, the probability of response does vary according to receptor agonist, and can be enhanced by co-stimulation with NO. Given the close proximity between the astrocytic endfeed and CNS capillary and neuronal networks, but of which generate NO, there is potential for this crosstalk to modulate the activity of astrocytes in vivo.
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Cambray-Deakin, M. "Astrocytes : targets for neuroactive substances." Thesis, Open University, 1985. http://oro.open.ac.uk/56910/.
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Cahoy, John David. "Genomic analysis of highly purified astrocytes reveals in vivo astrocyte gene expression : a new resource for understanding astrocyte development and function /." May be available electronically:, 2007. http://proquest.umi.com/login?COPT=REJTPTU1MTUmSU5UPTAmVkVSPTI=&clientId=12498.
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Mhyre, Andrew James. "Mechanisms of estrogen signaling in astrocytes /." Thesis, Connect to this title online; UW restricted, 2005. http://hdl.handle.net/1773/6266.
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Siushansian, Ramin. "Vitamin C transport by cerebral astrocytes." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq21315.pdf.
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Blaszczyk, Lucie. "Etude des cellules astrocytaires et microgliales thalamiques dans un modèle de douleur neuropathique chez le rat." Thesis, Bordeaux, 2015. http://www.theses.fr/2015BORD0081/document.
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La douleur chronique est une pathologie invalidante de longue durée notamment caractériséepar trois symptômes : l’allodynie (un stimulus non douloureux est perçu comme douloureux),l’hyperalgésie (un stimulus douloureux est perçu comme encore plus douloureux) et desdouleurs ambulatoires. Quand cette douleur est due à une lésion ou une dysfonction du systèmenerveux on parle de douleur neuropathique. Chez les patients et les modèles animaux dedouleurs neuropathiques, les études ont montré que les neurones thalamiques étaienthyperexcitables. Les cellules gliales, astrocytes et microglies, sont des partenaires synaptiquesimpliqués dans la transmission et la plasticité synaptique et pourraient être impliqués dans cephénomène. En effet, ces cellules peuvent modifier leur phénotype lorsque le système nerveuxest affecté, elles sont réactives : leur morphologie est hypertrophiée, l’expression d’ARNm et deprotéines comme iba-1 (ionized binding-adaptor molecule 1) et CD11b/c (cluster ofdifferentiation 11b/c) pour les cellules microgliales et GFAP (glial fibrillary acidic protein) etS100β (S100 calcium binding protein β) pour les cellules astrocytaires est augmentée. Ellespeuvent également libérer des molécules pro-inflammatoires. Tout ceci pourrait générer ouamplifier l’hyperexcitabilité des neurones présents dans le thalamus.Mon travail de thèse a consisté en l’étude des astrocytes et de la microglie thalamique dans lemodèle de douleurs neuropathiques de ligature des nerfs spinaux L5-L6 du nerf sciatique (spinalnerve ligation, SNL). Les symptômes d’allodynie et d’hyperalgésie mécaniques ont étécaractérisés par le test des filaments de von Frey et les douleurs ambulatoires par le test dedistribution pondéral dynamique. L’expression des ARNm de marqueurs gliaux a été étudiée parune approche de qRT-PCR sur des prélèvements thalamiques et sur des noyaux thalamiquesobtenus par microdissection au laser. L’expression neurochimique des marqueurs iba-1,CD11b/c, Cathepsine S, GFAP et S100β a été étudié par immunohistofluorescence en quantifiantle nombre de cellules immunopositives et la surface occupée par les marqueurs. Toutes cesexpériences ont été réalisées à J14 et J28 après la chirurgie.A J14, les animaux SNL développent des symptômes d’allodynie et d’hyperalgésie mécaniqueainsi que des douleurs ambulatoires. Chez ces animaux, les cellules microgliales thalamiquesprésentent des signes de réactivité avec l’augmentation de l’expression des ARNm desmarqueurs CTSS et CX3CR1, le récepteur de la fractalkine, marqueurs connus pour leursimplications dans l’hyperexcitabilité neuronale spinale en conditions de douleursneuropathiques. De plus, l’expression neurochimique des marqueurs gliaux étudiés est diminuéece qui se traduit notamment par une diminution du nombre de cellules immunopositives pources marqueurs chez les animaux SNL. A J28, les symptômes douloureux sont maintenus. De plus,la réactivité microgliale décelée à J14 par qRT-PCR est toujours présente avec l’augmentation del’expression de l’ARNm codant pour la fractalkine (CX3CL1), partenaire de la voieCTSS/CX3CR1/CX3CL1. La diminution de l’expression neurochimique thalamique desmarqueurs gliaux chez les animaux SNL était transitoire et n’est plus présente à J28. Enrevanche, des signes de réactivité astrocytaire thalamique ont été mis en évidence chez lesanimaux SNL.Ainsi, ce travail dévoile une ambivalence au niveau des altérations de la glie thalamique dans cemodèle SNL: une diminution précoce de l’expression des marqueurs gliaux thalamiques suivied’une réactivité astrocytaire plus tardive concomitante à des signes de réactivité microgliale. Denombreuses expériences sont encore nécessaires pour appréhender l’impact de cetteambivalence gliale thalamique inédite dans un contexte de douleur neuropathiqueChronic pain is an incapacitating and long lasting pathology mainly characterized by threesymptoms: allodynia (a non painful stimulus is perceived as painful), hyperalgesia (a painfulstimulus is perceived as more painful) and ambulatory pains. When chronic pain is due to alesion or dysfunction of nervous system it is called neuropathic pain. In both patients and animalmodels of neuropathic pain, researchers found that thalamic neurons are hyperexcitable. Glialcells, astrocytes and microglia, are strong synaptic partners involved in synaptic transmissionand plasticity and therefore could be involved in this phenomenon. Indeed, these cells canmodify their phenotype when nervous system is damaged. They become reactive: theirmorphology is hypertrophied, mRNA and protein expression of iba-1 (ionized binding-adaptormolecule 1) and CD11b/c (cluster of differentiation 11b/c) for microglia and GFAP (glialfibrillary acidic protein) and S100β (S100 calcium binding protein β) for astrocytes is increased.They could also release pro-inflammatory molecules. All of these could contribute to generate oramplify the thalamic neuronal hyperexcitability.In my PhD work I studied thalamic astrocytes and microglia in a rat neuropathic pain model ofL5-L6 spinal nerves ligation (SNL). Mechanical allodynia and hyperalgesia were characterizedwith von Frey filament test and ambulatory pain with dynamic weight bearing apparatus. mRNAexpression of glial markers were studied with qRT-PCR technique on thalamic punches andlaser-microdissected nuclei. Neurochemical expressions of iba-1, CD11b/c, cathepsin S, GFAPand S100β markers were quantified using an immunohistofluorescence approach to count thenumber of immunopositive cells and surface stained by these markers. All these experimentswere done at D14 and D28 after surgery.At D14, SNL animals develop mechanical allodynia and hyperalgesia as well as ambulatory pain..For these animals, thalamic microglial cells showed signs of reactivity with the increase mRNAexpression of CTSS and CX3CR1, fractalkine receptor, well known markers involved in spinalneuronal hyperexcitability under neuropathic pain conditions. In addition, the number ofimmunopositive cells for the glial markers is decreased in SNL animals. At D28, the neuropathicpain symptoms are still present. Furthermore, thalamic microglial reactivity found at D14 withqRT-PCRm method is still present with the increased mRNA expression of fractalkine (CX3CL1),partner of CTSS/CX3CR1/CX3CL1 pathway. The decreased neurochemical expression of glialmarkers found at D14 was transient as I didn’t find this result at D28. However, thalamicastrocytic reactivity was found at D28 in SNL animals.So, this work reveal a new glial process at thalamic level in this SNL model of neuropathic pain :an early decreased expression of glial markers and then a later thalamic astrocytic reactivityconcomitant with signs of thalamic microglial reactivity. Numerous studies are required toexplore the role of such novel ambivalent glial alterations in the context of neuropathic pain
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Chen, Xiaoqian. "The identification of 14-3-3[gamma] in astrocytes and its mechanism in protecting astrocytes from ischemia /." View Abstract or Full-Text, 2002. http://library.ust.hk/cgi/db/thesis.pl?BIOL%202002%20CHEN.
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Thesis (Ph. D.)--Hong Kong University of Science and Technology, 2002.Includes bibliographical references (leaves 180-202). Also available in electronic version. Access restricted to campus users.
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Carney, Karen. "Caractérisation Protéomique Des Prolongements Astrocytaires au Cours de la Plasticité Synaptique." Thesis, Bordeaux, 2014. http://www.theses.fr/2014BORD0270/document.
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Les astrocytes sont les cellules les plus abondantes dans le cerveau où ils sontimpliquées dans une myriade de fonctions telles que la neurogénèse, l’homéostasieionique, le soutien métabolique, l’élimination des substances toxiques et dans laréponse aux lésions cérébrales. Des altérations fonctionnelles des astrocytes ont étéassociées avec des pathologies telles que l’épilepsie, la depression et laschizophrénie. A ce titre, l’étude de la contribution astrocytaire aux fonctionssynaptiques revêt un intérêt clinique et sociétal assez conséquent. Dans cette thèse,j’ai évalué le potentiel de plusieurs préparations permettant l’analyse des protéinesastrocytaires impliquées dans la plasticité synaptique et j’ai utilisé celle qui se prêtaitle mieux à la quantification des niveaux de protéines astrocytaires qui se trouventêtre régulées dans différent modèles de plasticité synaptique. J’ai caractériséplusieurs préparations qui peuvent être utilisées pour évaluer la contribution desastrocytes à la plasticité synaptique et j’ai identifié de nombreuses protéinesastrocytaires régulées par la plasticité synaptique et qui sont susceptibles d’êtreciblées lors de prochaines études destinées à identifier les mécanismes d’action desastrocytes dans un contexte physiologique et pathologiqueAstrocytes are the most abundant cell type in the brain and mediate a myriad offunctions, including neurogenesis, ion homeostasis, metabolic support, clearance oftoxic substances and responses to brain injuries. Alterations in astrocyte functionhave been linked with neurological disorders such as epilepsy, depression, dementiaand schizophrenia, and thus the continued study of astrocytic contributions tosynaptic function are of clinical and societal relevance. In this thesis I have evaluatedthe potential utility of several preparations for the assessment of astrocyte proteinsinvolved in the regulation of synaptic plasticity, and employed the most suitable ofthese preparations to measure regulation in astrocyte protein levels in models ofsynaptic plasticity. I have characterized several preparations that can be used toevaluate astrocyte contributions to synaptic plasticity and identified numerousastrocyte-enriched proteins regulated by synaptic plasticity that can be targeted infuture studies to elaborate upon the mechanisms of action of astrocytes in bothphysiological and pathological contexts
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Morgan, Sarah V. "Tight junction protein expression in human astrocytes." Thesis, University of Sheffield, 2016. http://etheses.whiterose.ac.uk/14403/.
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Tight junctions are formed from a complex of different individual proteins. These complexes are expressed by epithelial cells and form an intercellular barrier which restricts and regulates paracellular permeability. Tight junction proteins have also been shown to be expressed in non-epithelial cells which do not form tight junctions, including astrocytes. The function(s) of these proteins within non-epithelial cells, however, remains unclear. This study aims to characterise the expression of tight junction proteins in astrocytes and investigate the function(s) of these proteins in these cells. The expression of the tight junction proteins occludin, claudin-5 and zonula occludens-1 (ZO-1) was characterised in vitro in both human primary astrocytes and the 1321N1 human astrocytoma cell line and in vivo in human autopsy brain samples. The function(s) of occludin was investigated using a pull-down protein binding assay and mass spectrometry analysis to identify putative binding partners for this protein in astrocytes. The current study demonstrates astrocytic and nuclear expression of occludin and ZO-1 in vitro and in vivo. The expression of claudin 5 in astrocytes remains difficult to determine due to contradictory evidence in which the astrocytic expression of this protein in vitro is not supported in vivo. Putative binding partners were also identified for the N- and C-terminal domains of occludin. Many of these proteins have functions in RNA metabolic processes, consequently their identification as putative occludin binding partners implicates occludin in functions beyond the formation of the tight junction complex. Although these interactions have not yet been validated, this study’s findings provide a platform upon which future research can be constructed.
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O'Brien, Emma Rosemary. "The role of astrocytes in brain metastasis." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:60efc7bd-4f00-4e84-a964-c4ef55009dfb.
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Supattapone, Surachai. "The effects of endothelin on rat astrocytes." Thesis, University of Oxford, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.279908.
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Nash, Besma. "The dual role of astrocytes in myelination." Thesis, University of Glasgow, 2010. http://theses.gla.ac.uk/2378/.
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Astrocytes are the most abundant cell within the central nervous system (CNS) and yet despite this, the true extent of their role in health and disease has not been fully elucidated. In the undamaged CNS, they are termed quiescent, where they maintain homeostasis. However, after injury or disease astrocytes become reactive where they are described as a physical and molecular barrier to regeneration. Emerging literature has suggested the existence of an additional phenotype of astrocyte, termed the activated astrocyte. These astrocytes are thought to enhance regeneration by creating a more growth-permissive environment for repair. In addition, it has also been reported that astrocytes may play a role in regulating myelination; however, it is unclear how the phenotype of the astrocytes may affect this process. Therefore, this thesis will focus on the variable phenotypic state of astrocytes and subsequently how this relates to their ability to support myelination. Using an in vitro myelinating culture, where dissociated spinal cord cells were plated on a monolayer of astrocytes, myelination can be followed over time. Since it is hypothesised that astrocytes can affect myelination we used two protocols known to affect the reactive status of the astrocyte, i) activate the astrocytes by treating with ciliary neurotrophic factor (CNTF) or ii) induce a quiescent astrocyte state by plating them on Tenascin C (TnC). It is hypothesised that CNTF changes the activation state of the astrocyte therefore making it more supportive to myelination. The addition of the astrocyte derived factor ciliary neurotrophic factor (CNTF) was shown to enhance myelination. My results demonstrate that CNTF addition does not lead to an increase in oligodendrocyte or microglia cell numbers or an increase in the diameter of the neurites, thus suggesting that this CNTF-induced increase in myelination is mediated via the astrocyte. Conversely, culturing astrocytes on the extracellular matrix molecule Tenascin-C (TnC), a method to make the astrocytes quiescent (Holley et al., 2005), resulted in a reduction in myelination. Astrocytes cultured on TnC were shown have decreased expression of nestin, which is typically a marker for reactivity. A microarray gene study comparing gene expression of the various astrocyte phenotypes identified CXCL10 to be upregulated in astrocytes on TnC. Furthermore, the addition of CXCL10 into the myelination cultures resulted in a decrease in myelination. Conversely, the addition of anti-CXCL10 to myelinating cultures on quiescent astrocytes increased myelination. Taken together, these data indicate that the astrocyte phenotype has considerable influence on myelination; where activated astrocytes support myelination whilst quiescent astrocytes do not. The identification of factors which may modify astrocyte phenotypes could lead to potential therapeutic strategies for CNS pathologies.
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Hashemian, Sanazalsadat. "Interaction between nerve fiber formation and astrocytes." Doctoral thesis, Umeå universitet, Histologi med cellbiologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-88366.
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Parkinson’s disease, the second most common neurodegenerative disorder,is characterized by loss of nigrostriatal dopaminergic neurons. To date,there is no defined cause and cure for the disease. An ideal treatmentstrategy is to replace the lost neurons by transplanting fetal dopaminergicneurons to the brain of parkinsonian patients. Clinical trials have beenperformed and the outcome was variable where one significant obstaclewas the limited graft reinnervation of the host brain. To study this issue,organotypic tissue culture can be utilized to monitor dopaminergic nervefiber outgrowth in vitro and their association with astrocytes. Using thisculture technique, dopaminergic nerve fibers appear in twomorphologically and temporally different types. The early appearing nervefibers are formed in the absence of astrocytes, reach long distances, andare called non-glial-associated tyrosine hydroxylase (TH) -positive nervefibers. After a few days, the second sequence of nerve fibers, the glialassociatedTH-positive nerve fibers, are formed, and their growth arelimited to the presence of astrocytes, that migrate and form a monolayersurrounding the plated tissue. The aim of this thesis was to study theinteraction between nerve fiber formation and astrocytes with a specialfocus on the long-distance growing nerve fibers. Ventral mesencephalic(VM) organotypic slice cultures from embryonic day (E) 12, E14, and E18were incubated for 14, 21, 28, and 35 days in vitro (DIV). The resultsrevealed that the two morphologically different processes were found incultures from the younger stages, while no non-glial-associated growthwas found in cultures of tissue from E18. Instead neurons had migratedonto the migrating astrocytes. Astrocytes migrated longer distances intissue from older stages, and the migration reached a plateau at 21 DIV.Co-cultures of E14 VM tissue pieces and cell suspension of matureastrocytes promoted migration of neurons, as seen in E18 cultures. Thus,9the maturity of the astrocytes was an important factor for nerve fiberoutgrowth. Hence, targeting molecules secreted by astrocytes might bebeneficial for regeneration. Chondroitin sulfate proteoglycan (CSPG), amember of proteoglycan family, is produced by the astrocytes and has adual role of being permissive during development and inhibitory afterbrain injury in adult brain. Cultures were treated with chondroitinase ABC(ChABC) or methyl-umbelliferyl-β-D-xyloside (β-xyloside) in twodifferent protocols, early and late treatments. The results from the earlytreated cultures showed that both compounds inhibited the outgrowth ofnerve fibers and astrocytic migration in cultures from E14 tissue, while β-xyloside but not ChABC promoted the non-glial-associated growth incultures derived from E18 fetuses. In addition, β-xyloside but not ChABCinhibited neuronal migration in E18 cultures. Taken together, β-xylosideappeared more effective than ChABC in promoting nerve fiber growth.Another potential candidate, integrin-associated protein CD47, was studiedbecause of its role in synaptogenesis, which is important for nerve fibergrowth. Cultures from E14 CD47 knockout (CD47-/-) mice were plated andcompared to their wildtypes. CD47-/- cultures displayed a massive and longnon-glial-associated TH-positive nerve fiber outgrowth despite theirnormal astrocytic migration. Blocking either signal regulatory protein-α(SIRPα) or thrombospondin-1 (TSP-1), which bind to CD47, had nogrowth promoting effect. In conclusion, to promote nerve growth, youngertissue can grow for longer distances than older tissue, and inhibiting CSPGproduction promotes nerve growth in older tissue, while gene deletion ofCD47 makes the astrocytes permissive for a robust nerve fiber growth.
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Mead, Carole. "Studies of toxic responses in cultured astrocytes." Thesis, University of Salford, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244928.
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Marschinke, Franziska. "From dopamine nerve fiber formation to astrocytes." Doctoral thesis, Umeå : Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umeå University, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-20615.
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CHIACCHIARETTA, MARTINA. "Impact of graphene nanosheets on primary astrocytes." Doctoral thesis, Università degli studi di Genova, 2018. http://hdl.handle.net/11567/929833.
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Tsang, Yuen Ting. "Expression of brain-derived neurotrophic factor in reactive astrocytes provides neuroprotection to SH-SY5Y cells against six-hydroxydopamine toxicity invitro." HKBU Institutional Repository, 2012. https://repository.hkbu.edu.hk/etd_ra/1392.
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Smith, Maria Civita. "MAPPING ASTROCYTE DEVELOPMENT IN THE DORSAL CORTEX OF THE MOUSE BRAIN." Case Western Reserve University School of Graduate Studies / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=case1373039738.
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Nadkarni, Suhita. "Dynamics of Dressed Neurons: Modeling the Neural-Glial Circuit and Exploring its Normal and Pathological Implications." Ohio : Ohio University, 2005. http://www.ohiolink.edu/etd/view.cgi?ohiou1125689320.
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Le, Douce Juliette. "Altération métabolique et déficit synaptique dans la maladie d'Alzheimer : rôle de la PHGDH astrocytaire." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066552/document.
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Les patients atteints de la MA souffrent d'altérations métaboliques et synaptiques précoces. Via la glycolyse et le cycle de Krebs, le métabolisme du glucose permet la production d'ATP, essentielle à l'activité et la plasticité synaptique. Contrairement aux neurones, les astrocytes utilisent majoritairement la glycolyse pour métaboliser le glucose. En plus de la production d'énergie, la glycolyse fournit les précurseurs indispensables à la synthèse de biomolécules comme la L-sérine. Cet acide aminé est produit à partir du glucose par la déviation du 3-phosphoglycérate (3PG), un intermédiaire glycolytique, via l'enzyme 3-phosphoglycérate déshydrogénase (PHGDH), exprimée spécifiquement dans les astrocytes. La L-sérine est le précurseur de la D-sérine, le principal co-agoniste des NMDAR nécessaires à l'activité et la plasticité synaptique.Nous avons utilisé des souris 3xTg-AD, un modèle développant une MA progressive, afin d'étudier si une altération de la production de L-/D-sérine pouvait contribuer à des déficits synaptiques.A 6 mois, lorsque les souris 3xTg-AD ne possèdent pas encore de plaques amyloïdes dans l'hippocampe, nous avons observé in vivo une diminution du métabolisme du glucose, de la concentration de L-sérine et des déficits synaptiques (LTP). L'expression locale de la PHGDH est aussi altérée. L'application de D-sérine restaure complètement les déficits de LTP chez les souris 3xTg-AD.Ces données supportent l'hypothèse qu'un déficit de production de L-sérine par les astrocytes médié par une diminution du flux glycolytique serait responsable de l'altération synaptique observée dans l'hippocampe des souris 3xTg-ADAn early alteration of both cerebral glucose metabolism and synaptic activity has been consistently described in Alzheimer's disease (AD) patients. Metabolism of glucose via glycolysis and the citric acid cycle produces ATP that is essential for synaptic activity and plasticity. In the brain, glucose is predominantly processed glycolytically into astrocytes and not by neurons. Beyond ATP production, a major function of aerobic glycolysis is to provide precursors to support macromolecular synthesis. L-serine, generated from glucose through diversion of the glycolytic intermediate 3-phosphoglycerate (3PG) into the phosphorylated pathway, is only produced in astrocytes by 3-phosphoglycerate dehydrogenase (PHGDH), selectively expressed in those glial cells. L-serine is the precursor of D-serine, the main co-agonist of synaptic NMDAR, required for synaptic activity and plasticity. We used 3xTg-AD mice, which develop a progressive pathology, to investigate whether a defective production of L-/D-serine contributes to early synaptic deficits in AD. We found that 3xTg-AD mice display early in vivo alterations of glucose metabolism, synaptic deficits (LTP) in the CA1 region and also lower concentration of L-serine. The local expression of PHGDH was significantly altered. Exogenous D-serine completely rescued LTP in 3xTg-AD mice. These data support the hypothesis that a deficit of L-serine synthesis by astrocytes likely mediated by a decreased glycolytic flux may be responsible for the synaptic alteration mediated by NMDAR in the hippocampus of 3xTg-AD mice
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Syed, Nasser. "Arginine vasopressin and somatostatin receptors in rat astrocytes." [Ames, Iowa : Iowa State University], 2006.
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Small, Lorne N. (Lorne Neil). "The composition of inclusions specific to Gomori astrocytes." Thesis, McGill University, 1994. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=22805.
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Gomori astrocytes, found in periventricular nuclei of the hypothalamus, contain large, electron dense, pleomorphic inclusions. The Gomori inclusions emit an orange-red autofluorescence, consistent with porphyrin and stain with diaminobenzidine, indicative of peroxidase activity. Although the orange-red autofluorescence is suggestive of porphyrins, it has not been shown that porphyrins concentrate in Gomori inclusions. The present study shows that a radioactively labeled porphyrin precursor does localize to Gomori inclusions. The peroxidase activity is thought to result from redox active transition metals in the inclusions. This study addresses transition metal content of the inclusions. Using radioautography, it was determined that Gomori inclusions sequester and concentrate chromium. Additionally, energy dispersive X-ray microanalysis shows that nascent Gomori inclusions sequester iron, but that this is eventually replaced by copper. The results of this study elucidate the developmental trajectory of Gomori inclusions and provide a basis for understanding their role in neuropathology.
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Cookson, Mark R. "Studies of activation and toxicity in cultured astrocytes." Thesis, University of Salford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308094.
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Vladimirov, Andrew A. "Metabolic receptor cross-talk and excitotoxicity in astrocytes." Thesis, University of Bristol, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.399955.
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Martin-Biran, Magali. "Etude par spectroscopie de RMN du métabolisme des neurones et des astrocytes en culture primaire." Bordeaux 2, 1994. http://www.theses.fr/1994BOR28314.
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Dans la perspective de mieux comprendre les phénomènes de compartimentation cellulaire au sein du système nerveux central, nous avons choisi de définir les caractéristiques métaboliques des neurones et des astrocytes en culture primaire homogène. Le devenir métabolique du [1-13C]glucose dans les neurones et les astrocytes cérébelleux, de même que dans les astrocytes corticaux, a été caractérisé par spectroscopie de RMN. Les astrocytes, contrairement aux neurones, synthétisent la glutamine. La maturation des voies de biosynthèse de cet acide aminé est retardée dans les astrocytes cérébelleux par rapport aux astrocytes corticaux. La quantification des flux du catabolisme du glucose exogène a été réalisée. Ces résultats ont montré l'utilisation quasi-exclusive du glucose comme source de carbone par les neurones, alors que les astrocytes utilisent des sources plus diversifiées (glucose, acides aminés exogènes, sources endogènes de carbone). De même, l'activité de la voie de la pyruvate carboxylase est de faible importance dans les neurones, ce qui implique la nécessité d'un apport de carbone extérieur pour ces cellules. Cette étude nous a permis de mettre en évidence des composés synthétisés et libérés par les astrocytes dans le milieu extracellulaire, l'alanine et le citrate, susceptibles de servir de navettes de carbone et/ou d'azote, autres que la glutamine, entre les neurones et les astrocytes. Les données acquises par RMN du 31P ont révélé des charges énergétiques très similaires dans les neurones et les astrocytes cérébelleux, de même que dans le cervelet entier. Des différences concernant les composés liés au métabolisme des membranes ont pu être observées. Une étude du développement du cervelet de rat a été réalisée par RMN du 31P et du 1H, démontrant l'existence d'un contenu élevé en acétate dans le cervelet à la naissance. Celui-ci décroît lors des 1ers jours postnataux, alors que la concentration en NAA augmenteIn order to investigate the cellular compartmentation of the central nervous system, we first defined the metabolic properties of neurons and astrocytes in homogenous primary culture. The metabolic fate of [1-13C]glucose in cerebellar neurons and astrocytes, as well as in cortical astrocytes, was characterized by NMR spectroscopy. The astrocytes, contrary to neurons, synthesized glutamine. The maturation of the glutamine synthesis pathway was delayed in cerebellar astrocytes, as compared to cortical astrocytes. The fluxes involved in exogenous glucose utilization were quantified. The results demonstrated that if neurons used exclusively glucose as carbon source to fuel the Krebs cycle, the carbon sources for astrocytes were diversified (glucose, exogenous amino acids, endogenous carbon sources). In the same way, the pyruvate carboxylase activity was of minor importance in neurons, that implied the need for these cells of exogenous carbon substrates. We evidenced that alanine and citrate were also synthesized by astrocytes and exported to their extracellular medium. These metabolites may play a role as carbon and/or nitrogen shuttles betwen neurons and astrocytes. 31P NMR data showed similar energy charges in cerebellar neurons, astrocytes and in the cerebellum. Differences in the content of metabolites linked to membrane metabolism were observed. The postnatal development of the cerebellum was studied using 31P and 1H NMR spectroscopy. A large content of acetate was evidenced at birth, that decreased during the first postnatal days whereas the NAA content increased
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Abjean, Laurene. "Les astrocytes réactifs, des partenaires anti-agrégants dans la maladie de Huntington : identification des mécanismes impliqués dans le dialogue neurone-astrocyte." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS088.
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La maladie de Huntington (MH) est une maladie neurodégénérative causée par une extension de répétitions du codon CAG dans le gène de la Huntingtine (Htt). Cette maladie est caractérisée par la mort des neurones striataux et la présence d’agrégats de Htt mutée (mHtt). De plus, au cours de la MH, les astrocytes, qui sont essentiels au bon fonctionnement neuronal, changent d’état et deviennent réactifs. La réactivité astrocytaire est caractérisée par des changements morphologiques et transcriptomiques mais l’impact fonctionnel de cette réactivité reste peu compris.Afin d’étudier le rôle des astrocytes réactifs dans la MH, nous avons utilisé des vecteurs viraux récemment développés par notre équipe, qui induisent ou bloquent la réactivité astrocytaire in vivo en ciblant la voie JAK2-STAT3. Nous avons montré que les astrocytes réactifs diminuent le nombre et la taille des agrégats de mHtt majoritairement présents dans les neurones. Ceci est associé à l’amélioration de plusieurs altérations neuronales observées dans ces modèles. Une analyse transcriptomique réalisée sur des astrocytes réactifs révèle des changements majeurs d’expression de gènes liés aux systèmes de protéostasie. De plus, l’activité du lysosome et du protéasome est augmentée dans les astrocytes réactifs de souris modèles de la MH. Nous montrons également que les astrocytes réactifs éliminent plus efficacement leurs propres agrégats de mHtt, suggérant qu’au cours de la MH, ces cellules pourraient dégrader plus efficacement la mHtt provenant des neurones. De plus, certaines protéines chaperonnes sont induites dans les astrocytes réactifs. En particulier, la co-chaperonne DNAJB1/Hsp40 est surexprimée dans les astrocytes réactifs et est retrouvée dans les exosomes isolés à partir de striata de souris MH. Des expériences de gain et perte de fonction suggèrent que cette chaperonne est impliquée dans les effets bénéfiques des astrocytes réactifs sur l’agrégation de la mHtt et l’état des neurones. Les astrocytes réactifs pourraient donc libérer des protéines anti-agrégantes qui favorise l’élimination de la mHtt dans les neurones.Notre étude montre que les astrocytes peuvent, en devenant réactifs au cours de la MH, acquérir des propriétés bénéfiques pour les neurones et favoriser, via un dialogue complexe avec les neurones, l’élimination des agrégats de mHttHuntington’s disease (HD) is a hereditary neurodegenerative disease caused by an expansion of CAG codons in the Huntingtin gene. It is characterized by the death of striatal neurons and the presence of mutant Huntingtin (mHtt) aggregates. In pathological conditions, as in HD, astrocytes change and become reactive. Astrocyte reactivity is characterized by morphological and significant transcriptomic changes. Astrocytes are essential for the proper functioning of neurons but the functional changes associated with reactivity are still unclear.To better understand the roles played by reactive astrocytes in HD, we took advantage of our recently developed viral vectors that infect selectively astrocytes in vivo and either block or induce reactivity, through manipulation of the JAK2-STAT3 pathway. We used these vectors in two complementary mouse models of HD and found that reactive astrocytes decrease the number and the size of mHtt aggregates that mainly form in neurons. Reduced mHtt aggregation was associated with improvement of neuronal alterations observed in our mouse models of HD. A genome-wide transcriptomic analysis was performed on acutely sorted reactive astrocytes and revealed an enrichment in genes linked to proteolysis. Lysosomal and proteosomal activities were also increased in reactive astrocytes in HD mice. Moreover, we show that reactive astrocytes degrade more efficiently their own mHtt aggregates, suggesting that these cells could siphon mHtt away from neurons. Alternatively, several chaperones were induced in reactive astrocytes. In particular, the co-chaperone DNAJB1/Hsp40 was upregulated in reactive astrocytes and was present in exosomal fraction from HD mouse striatum. Loss and gain of function experiments suggest that this chaperone is involved in the beneficial effects of reactive astrocytes on mHtt aggregation and neuronal status. Therefore, reactive astrocytes could release anti-aggregation proteins that could promote mHtt clearance in neurons.Overall, our data show that astrocytes, by becoming reactive in HD, develop a protective response that involves complex bidirectional signaling with neurons to reduce mHtt aggregation
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Moreno, García Álvaro. "Endocannabinoid modulation of astroglial cells in multiple sclerosis." Electronic Thesis or Diss., Bordeaux, 2022. http://www.theses.fr/2022BORD0171.
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La sclérose en plaques (SEP) est une maladie inflammatoire chronique à médiation immunitaire du système nerveux central et est une cause majeure de handicap chez les jeunes adultes. Il est bien établi que l'activation des astrocytes est à l'origine de l'inflammation chronique et de la neurodégénérescence dans le modèle d'encéphalomyélite auto-immune expérimentale (EAE) de la SEP et que la modulation in vivo de la signalisation astrocytaire a des effets bénéfiques sur la progression de la maladie. L'identification des facteurs conduisant à l'activité pathogène des astrocytes dans la SEP contribuera donc au développement de nouvelles stratégies de traitement plus efficaces. Dans ce contexte, a récemment été identifiée dans la SEP une population neurotoxique d'astrocytes réactifs, induits par la microglie activée, qui contribue à la mort des neurones et des oligodendrocytes.Les astrocytes présentent une dynamique Ca2+ complexe qui est fondamentale pour la signalisation intracellulaire ainsi que la communication intercellulaire. Les signaux Ca2+ dépendants de l'activité dans les astrocytes régulent directement les fonctions biologiques de ces cellules et affectent l'intégration et le traitement des informations synaptiques. En effet, les astrocytes répondent par une élévation du Ca2+ cytosolique à une grande variété de neurotransmetteurs libérés par les neurones. Ils libèrent ensuite une pléthore de molécules neuroactives, appelées gliotransmetteurs. Des astrocytes réactifs présentant une signalisation déréglée du Ca2+ ont été trouvés dans plusieurs troubles neurologiques. Cependant, la dynamique du Ca2+ des astrocytes n'a pas encore été étudiée dans le contexte de la SEP.Les astrocytes et la microglie sont modulés par les endocannabinoïdes et participent à la biosynthèse et au métabolisme de ces composés. Cependant, le rôle des cellules neurogliales en tant que cibles et médiateurs de la signalisation endocannabinoïde dans la SEP reste très peu compris. Les (endo)cannabinoïdes agissant par l'intermédiaire des récepteurs cannabinoïdes de type 1 (CB1Rs) permettent de contrôler les symptômes de la SEP. Ces effets bénéfiques sont principalement modulés par l'activation des CB1Rs neuronaux qui engagent une protection contre l'excitotoxicité du glutamate. D'autre part, les CB1Rs exprimés dans les astrocytes induisent des élévations intracellulaires de Ca2+ qui favorisent la libération de glutamate. Ce mécanisme sous-tend l'altération de la mémoire de travail par les cannabinoïdes aigus chez les rongeurs et pourrait contribuer aux événements excitotoxiques dans les conditions neurodégénératives telles que la SEP.Dans ce travail, nous avons abordé plusieurs objectifs visant à déchiffrer le rôle du système endocannabinoïde dans la modulation des astrocytes pendant la SEP. Dans le modèle EAE de SEP, nous avons 1) étudié la dynamique temporelle de la dérégulation de la signalisation endocannabinoïde dans les astrocytes réactifs, 2) caractérisé les changements dans la signalisation Ca2+ astrocytaire et 3) examiné le rôle des CB1Rs astrogliaux pendant la démyélinisation auto-immune. Nos résultats montrent que l'activation des astrocytes au cours de l'EAE implique des altérations transcriptionnelles précoces affectant les molécules associées à la signalisation endocannabinoïde. Ensuite, nous avons identifié les CB1Rs comme régulateurs cruciaux de la dynamique du Ca2+ astrocytaire dans le cortex de la souris in vivo et découvert une signalisation aberrante du Ca2+ dans la SEP. Enfin, nous dévoilons que les CB1Rs astrocytaires exacerbent l'incapacité neurologique et la neuroinflammation au cours de l'EAE, ce qui met en évidence un rôle précédemment inattendu du système endocannabinoïde dans la physiopathologie de la myéline. Ces données élargissent les connaissances actuelles sur les mécanismes impliqués dans les bénéfices ainsi que les effets secondaires des traitements actuels de la SEP, ciblant les CB1RsMultiple sclerosis (MS) is an immune-mediated, chronic inflammatory disease of the central nervous system and a leading cause of disability in young adults. It is well-established that astrocyte activation drives chronic inflammation and neurodegeneration in the experimental autoimmune encephalomyelitis (EAE) model of MS and in vivo modulation of astrocyte signaling exhibits beneficial effects during disease progression. It is thus envisaged that the identification of factors driving pathogenic astrocyte activity in MS will contribute to the development of novel and more successful treatment strategies. In this context, a neurotoxic population of neurotoxic reactive astrocytes induced by activated microglia that contributes to the death of neurons and oligodendrocytes has been recently identified in MS.Astrocytes present complex and tightly controlled Ca2+ dynamics which are fundamental to intracellular signaling and intercellular communication. Activity-dependent Ca2+ signals in astrocyte regulate directly the biological functions of these cells and affect the integration and processing of synaptic information, modulating synaptic transmission, plasticity and behavior. Indeed, astrocytes respond with cytosolic Ca2+ elevations to a wide variety of neurotransmitters released by neurons and subsequently release a plethora of neuroactive molecules, called gliotransmitters, which comprise glutamate, ATP, D-serine and GABA. Reactive astrocytes displaying deregulated Ca2+ signaling have been found in several neurological disorders. However, astrocyte Ca2+ dynamics have not been investigated in the context of MS.Astrocytes and microglia are modulated by endocannabinoids and participate in the biosynthesis and metabolism of these compounds. However, the role of neuroglial cells as targets and mediators of endocannabinoid signaling in MS remains poorly understood. (Endo)cannabinoids acting through cannabinoid type 1 receptors (CB1Rs) exert symptom control in MS. These beneficial effects are mainly mediated by the activation of neuronal CB1Rs that engage protection from glutamate excitotoxicity. On the other hand, CB1Rs expressed in astrocytes induce intracellular Ca2+ elevations that promote glutamate release. This mechanism underlies working memory impairment by acute cannabinoids in rodents and may contribute to excitotoxic events in neurodegenerative conditions such as MS.In this work, we have addressed several objectives aimed at deciphering the role of the endocannabinoid system in modulating astrocytes during MS. In the EAE model of chronic MS we have 1) investigated the temporal dynamics of endocannabinoid signaling deregulation in reactive astrocytes, 2) characterized changes in astrocyte Ca2+ signaling and 3) examined the role of astroglial CB1Rs during autoimmune demyelination using conditional mutant mice. Our results show that astrocyte activation during EAE involves early transcriptional alterations affecting endocannabinoid signaling associated molecules. Secondly, we have identifies CB1Rs as crucial regulators of astrocytic Ca2+ dynamics in the mouse cortex in vivo and uncover aberrant Ca2+ signaling in MS. Lastly, we unveil that astrocyte CB1Rs exacerbate neurological disability and neuroinflammation during EAE pointing out to a previously unexpected role of the ECS in the pathophysiology of myelin. These data broaden current knowledge on the mechanisms involved in benefits/side effects of currently available MS treatments targeting CB1Rs and pave the way for the development of novel, more efficacious endocannabinoid system-modulating drugs to treat MS
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Eraso, Pichot Abel. "Adaptive regulation of calcium excitability and energy metabolism by CREB-dependent transcription in astrocytes: study of the mechanisms governing astrocyte plasticity." Doctoral thesis, Universitat Autònoma de Barcelona, 2018. http://hdl.handle.net/10803/664170.
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Cada cop més evidencies suggereixen que els astròcits participen en les altes funcions cerebrals, controlant des de la transmissió sinàptica fins a les ones cerebrals globals i els processos d’aprenentatge i memòria. Diferents mecanismes han sigut proposats com a responsables d’aquests processos mediats per astròcits, entre ells, l’alliberació de gliotransmissors a partir de les senyals de calci així com la de lactat semblen els principals efectors. L’existència d’aquest control de les funcions cerebrals per part dels astròcits suggereix que aquestes cèl·lules poden regular les funcions cerebrals en resposta a experiència tan com les neurones, constituint el fenomen de plasticitat astrocitària. En neurones s’ha demostrat que el conegut factor de transcripció CREB, coordina les plasticitats sinàptica i intrínseca. El fet que, en astròcits, l’activació de CREB també està regulada per activitat cerebral, situa aquest factor de transcripció com a la diana ideal per promoure canvis dependents d’activitat en astròcits. En aquesta tesi hem analitzat l’efecte de l’activació de la transcripció depenent de CREB en astròcits, centrant-nos en l’excitabilitat del calci i en el metabolisme d’aquestes cèl·lules. Hem demostrat que l’activació de la transcripció depenent de CREB redueix les senyals citosòliques de calci a través del mitocondri a la vegada que augmenta l’alliberació de lactat, dos canvis que poden tenir impacte en la transmissió sinàptica. Una altra contribució important d’aquest estudi es l’anàlisi molecular dels mitocondris dels astròcits, que ha revelat que aquestes cèl·lules poden utilitzar metabòlits que no són glucosa, com ara àcids grassos, per respondre a les necessitats metabòliques energètiques. Els nostres resultats estableixen el CREB en astròcits con un eix de la plasticitat astrocitària i revelen la interacció entre la plasticitat i el metabolisme energètic en astròcits. Aquests descobriments constitueixen un avenç mecanístic i conceptual en el coneixement de la biologia dels astròcits i com aquestes cèl·lules poden controlar l’aprenentatge i la memòria.An increasing body of evidence suggests that astrocytes participate in higher-brain functions, controlling from synaptic transmission to global brain waves and learning and memory processes. Different mechanisms have been proposed to mediate these astrocyte-dependent processes, astrocytic lactate release and calcium-dependent gliotransmission being the main known effectors. The existence of control of brain functions by astrocytes suggests that astrocytes may shape brain functions in response to experience as much as neurons, thus constituting the phenomenon of astrocyte plasticity. In neurons, the transcription factor CREB is the best known coordinator of synaptic and intrinsic plasticity. The fact that, in astrocytes, CREB activation is also activity-dependent, positions CREB as an ideal target to promote plasticity-related changes in astrocytes, too. In this thesis, we have analyzed the effect of the activation of CREB-dependent transcription in astrocytes, specifically regarding calcium signals and metabolism. We have demonstrated that activation of CREB-dependent transcription reduces cytosolic calcium events via mitochondria and increases in lactate release, which may have impact on synaptic transmission. An important contribution of the study is the molecular analysis of astrocytic mitochondria, which has revealed that astrocytes may use fuels other than glucose such as fatty acids to meet basic energy metabolic demands. Taken together, our results establish astrocytic CREB as a hub in astrocyte-plasticity and shed light on the interplay between plasticity and energy metabolism in astrocytes; these findings constitute a conceptual and mechanistic advance in the knowledge of astrocytic biology and how these cells may control learning and memory.
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Blum, Andrew E. "G Protein-Coupled Receptor Regulation of ATP release from Astrocytes." Case Western Reserve University School of Graduate Studies / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1264192022.
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Stephan, Jonathan Verfasser], Christine R. [Akademischer Betreuer] Rose, and Dieter [Akademischer Betreuer] [Willbold. "Mechanisms of ammonium-induced depolarization of astrocytes in situ." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2011. http://d-nb.info/1015363687/34.
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Wrzos, Claudia. "The role of astrocytes for oligodendrocyte death and remyelination." Doctoral thesis, Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2012. http://hdl.handle.net/11858/00-1735-0000-000D-F1F4-E.
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Hirst, Warren David. "Serotonin receptors on astrocytes in vitro and in vivo." Thesis, Imperial College London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336284.
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Hernandez, Ernesto. "MORPHOLOGICAL ANALYSIS OF LARVAL DROSOPHILA ASTROCYTES IN THE VNC." Thesis, The University of Arizona, 2016. http://hdl.handle.net/10150/613064.
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Understanding the ongoing signaling between neurons and glial cells requires a detailed analysis
of glial cell morphology and physiology. In particular, the shapes and distribution of glial cells
help to dictate roles astrocytes play in regulating neuronal function. In each segment of the
ventral nerve cord of Drosophila, the neuropil is organized into distinct motor, interneuron, and
sensory neuropils. Each hemisegment of the neuropil is served by six astrocytes, with somas in
characteristic positions around the edge of neuropil. Here we use Flp-out (Ito et al., 1997) and
MultiColor FlpOut (Viswanathan et al., 2015) genetic constructs targeted to astrocytes via the
alrm-GAL4 driver (Doherty et al., 2009) to generate high-resolution images of astrocytes. Our
examination of individual astrocytes, and the interfaces between adjacent astrocytes has revealed
that (1) astrocytes have three morphological classes along with the identification of features such
as wrapping/following FasII-positive axon bundles, midline crossing, single protruding
processes, and a process leaving the CNS via the segmental nerve astrocytes display, (2) the
arbors of individual astrocytes span multiple functional neural domains and (3) astrocytic
branches have convoluted spatial domains, in which the finest distal branches of adjacent
astrocytes interweave with a variable, but small, amount of interdigitation.
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Stone, Rebecca. "Glutathione release from astrocytes; characterization and implications for neurodegeneration." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.395567.
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Gee, James Michael. "Genetic tools for imaging intracellular calcium dynamics in astrocytes." Thesis, The University of Utah, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10193205.
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New evidence afforded by advanced live-tissue imaging techniques indicates that astrocytes, the predominant glial cell subtype, play a far more active role in synaptic physiology than was previously appreciated. Evolved iterations of genetically encoded calcium indicators, primarily the GCaMP variants, have enabled high spatiotemporal resolution detection of intracellular activity, but are limited by few options for gene transfection and expression. The goal of this dissertation work was to develop novel GCaMP-based tools for straightforward optical interrogation of astrocytic activity in rodent models of neuropathology.
A Polr2a-targeted, Cre-dependent, CAG-driven, GCaMP5G-expressing reporter mouse line was constructed and designated “PC-G5-tdT”. Detection of positive cells was facilitated by an IRES-tdTomato tag. PC-G5-tdT proved effective in diverse developmental contexts and reported intracellular calcium dynamics in somas and fine processes of astrocytes, microglia and neurons. Electrophysiological and behavioral analyses failed to detect a detrimental impact of GCaMP5G expression on nervous system performance. In acute brain slices prepared from a model of endotoxemia-induced neuroinflammation, a stereotyped sequence of astrocytic intrinsic activity was observed over the acute phase. At early time points, frequent somatic and distal process transients were observed but progressively declined with process event frequency lagging behind the soma.
Several rat models of human neuropathology provide systems for researching basic mechanisms of disease. Unfortunately, transgenic rat technologies are immature and viral-based methods are hampered by side effects. In utero electroporation (IUE) is a proven method for transfecting astrocytes and neurons without major drawbacks. A toolset of IUE plasmids carrying CAG-driven, subcellular compartment-targeted GCaMP variants with optional cytosolic tdTomato co-expression was constructed. Stable expression was accomplished via random genomic integration of the reporter cassette through a binary plasmid system derived from the piggyBac transposon. Preparation- and age-specific patterns of activity were readily detected in astrocytes and neurons. In particular, organotypic slice culture astrocytes exhibited frequent global intrinsic transients whereas activity was restricted to distal astrocytic processes in acute brain slices prepared from older animals.
This work has already stimulated progress in the field of glial cell physiology. Future application of these tools will advance our understanding of glial-neuronal interaction and possibly inform development of improved disease modification strategies.
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Briens, Aurélien. "Contrôle du système d'activation du plasminogène par les astrocytes." Caen, 2014. http://www.theses.fr/2014CAEN3144.
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L’activation du plasminogène en plasmine par l’activateur tissulaire du plasminogène (tPA) initie la fibrinolyse dans le compartiment sanguin. Mais les enzymes de ce système sont aussi retrouvées dans le parenchyme cérébral où elles participent à des processus physiologiques comme la plasticité synaptique et à des processus pathologiques comme la mort neuronale excitotoxique en renforçant notamment la signalisation glutamatergique. Il doit donc exister des mécanismes cérébraux de régulation du système d’activation du plasminogène. Les astrocytes sont des cellules gliales coopérant avec les neurones pour contrôler la transmission et la plasticité synaptique, l’intégrité de la barrière hémato-encéphalique ou la neurotoxicité. Au cours des travaux réalisés pendant ma thèse, j’ai pu montrer que les astrocytes sont au cœur de la régulation des effets des acteurs du système d’activation du plasminogène. Ainsi, un processus de recyclage astrocytaire du tPA inhibé par le glutamate permet de contrôler ses effets excitotoxiques. De plus, les astrocytes constituent le premier type cellulaire identifié comme étant responsable de la clairance cérébrale de plasminogène et de plasmine grâce à un mécanisme de recapture de ces molécules potentialisé par l’activité extracellulaire de plasmine. Les astrocytes sont donc capables d’intégrer des informations provenant du milieu extracellulaire pour adapter les niveaux des membres du système d’activation du plasminogène et offrir aux neurones un environnement optimalActivation of plasminogen into plasmin by tissue-type Plasminogen Activator (tPA) initiates fibrinolysis in the vasculature. But enzymes of this system are also found in the brain parenchyma, where they are involved in physiological processes such as synaptic plasticity and in pathological processes such as excitotoxic neuronal death, notably by potentiating glutamatergic signaling. So there must be brain mechanisms regulating the plasminogen activation system. Astrocytes are glial cells cooperating with neurons to control synaptic transmission and plasticity, blood-brain barrier integrity or neurotoxicity. The work carried out in this thesis helped to highlight that astrocytes play a crucial role in the regulation of the effects of plasminogen activation system actors. Thus, a tPA recycling process mediated by astrocytes and inhibited by glutamate provides control of tPA pro-excitotoxic effects. Furthermore, astrocytes represent the first cell type responsible for the clearance of brain plasminogen and plasmin through a mechanism of uptake, a mechanism potentiated by extracellular plasmin activity. Hence, astrocytes can integrate information from the extracellular medium to match the levels of the members of the plasminogen activation system and provide an optimal environment to neurons
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Tournier, Cathy. "Regulation des map kinases dans les astrocytes de rat." Paris 11, 1996. http://www.theses.fr/1996PA11T007.
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Khan, Dilaware [Verfasser]. "The Relationship between Astrocytes, Inflammation and Epileptogenesis / Dilaware Khan." Bonn : Universitäts- und Landesbibliothek Bonn, 2017. http://d-nb.info/1140525824/34.
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Reyes, Reno Cervo. "The role of mitochondria and plasma membrane CA²⁺ transport systems in CA²⁺-dependent glutamate release from rat cortical astrocytes." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2009. https://www.mhsl.uab.edu/dt/2010r/reyes.pdf.
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PROVENZANO, FRANCESCA. "Mesenchymal stem cell-derived exosomes and exosome-shuttled miRNAs ameliorate the reactive and neurotoxic phenotype of mouse SOD1G93A astrocytes and human-derived SOD1A4V astrocytes." Doctoral thesis, Università degli studi di Genova, 2020. http://hdl.handle.net/11567/996729.
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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting primarily motor neurons (MNs) but involving also non-neuronal cells. Nowadays, it is well recognised that astrocytes, microglia and oligodendrocytes play a central role in disease onset and progression. In particular, astrocytes acquire a toxic phenotype characterized by an abnormal proliferation and by the release of neurotoxic factors, including pro-inflammatory cytokines (Lee et al., 2016). We have previously shown that the intravenous administration of mesenchymal stem cells (MSCs) in SOD1G93A mice prolonged survival, ameliorated motor skills and reduced gliosis and inflammation in spinal cord. These beneficial effects were not associated with MSC differentiation, being possibly mediated through paracrine mechanisms. We hypothesized that MSC-derived exosomes and exosome-shuttled miRNAs could mediate these positive effects. To verify our hypothesis we tested here the effects of exosomes derived from INF-activated MSCs on cultured astrocytes prepared from the spinal cord of 120 day-old late-symptomatic SOD1G93A mice. The phenotype of SOD1G93A astrocytes and the efficacy of the exosome treatment were characterized by Western blotting, confocal microscopy and ELISA immunoassay. Vimentin, GFAP and S100β, astrogliosis markers, were increased in astrocytes from 120 days-old SOD1G93A mice vs. age-matched WT astrocytes and their expression was reduced after exposure to exosomes. Nrf2, a booster of the response to oxidative stress, was decreased in SOD1G93A astrocytes vs. age-matched WT astrocytes. Exosome treatment normalized Nrf2 down-regulation both in the cytoplasm and nucleus. The quantification of TNF-α,IL-1β, IL-6 and CCL2 expression and release showed that these four pro-inflammatory factors were more expressed in and more efficiently released from SOD1G93A astrocytes and that the exposure to exosomes resulted in a significant decrease of their over-expression and release. Conversely, the anti-inflammatory cytokine IL-10 was decreased in SOD1G93A astrocytes and its expression was normalized after exposure to exosomes. Also NLRP3 expression, a marker of the multiprotein oligomer inflammasome, was increased in SOD1G93A astrocytes and the increase was reversed by exosomes. The amelioration of SOD1G93A astrocyte phenotype had a positive impact on MN viability in astrocyte-MN co-cultures. We observed a constant decrease of MN survival during time, both in control and exosome-treated co-cultures; however, the viability of MNs seeded on exosome-treated SOD1G93A astrocytes was always significantly higher when compared to co-cultures with untreated astrocytes. Exosome cargo was analysed for miRNAs and potential mediators of exosome activity were identified. The selected miRNAs showed a significant efficacy to reduce GFAP, IL-1β and TNF-α expression. Computational analysis highlighted their possible involvement in the modulation of NFκB and MAPK pathway activation, affecting numerous kinases and transcription factors involved in the regulation of these inflammatory signalling pathways. qPCR analysis confirmed the ability of these four miRNAs to reduce MAPK11 expression, regulating TNF-α synthesis. Unfortunately, the other selected targets were not affect by mimic transfection. Finally, we translated this study to human astrocytes derived from healthy donors and ALS patients carrying A4V-SOD1 mutation. Human ALS astrocytes were treated with exosomes derived from human MSCs, activated with INF. We observed only a slight amelioration of ALS astrocyte phenotype after the exosome treatment. Remarkably, analysis of MN viability showed an increased MN number in co-cultures with exosome-treated astrocytes compared to those co-cultured with untreated astrocytes. These results indicate that exosomes and exosome-shuttled miRNAs can reduce astrocyte reactivity and that this effect has a positive impact on MN viability. The in-vitro exosome activity, both in mouse and human models, paves the way to translational preclinical in-vivo treatments in SOD1G93A mice.
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Hamel, Rodolphe. "Biologie du virus zika dans les cellules cutanées et les astrocytes." Thesis, Montpellier, 2017. http://www.theses.fr/2017MONTT003.
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Le virus Zika (ZIKV), virus découvert pour la première fois à la fin des années quarante, est un arbovirus émergent récemment arrivé sous le feu des projecteurs à l’occasion d’une pandémie rapide à l’échelle mondiale. Appartenant à la famille des Flaviviridae, ce flavivirus est transmis par les moustiques du genre Aedes. Alors qu’on le croyait relativement peu pathogène, ce virus se révèle être la cause probable d’une vague de complications neurologiques, incluant l’apparition de microcéphalies et de syndromes de Guillain-Barré. De plus, il n’existe à l’heure actuelle ni vaccins ni traitements spécifiques, la lutte contre le virus se résumant largement à la mise en place de mesures de prévention contre la piqûre de moustiques et la lutte anti-vectorielle.Une meilleure connaissance de l’ensemble de la biologie du virus, depuis les modalités d’entrée dans l’organisme, en particulier au niveau cutanée, jusqu’aux mécanismes moléculaires intimes de la réplication du virus s’avère nécessaire. Par des approches moléculaires et cellulaires, nous avons mis en évidence le tropisme du virus, identifié ses récepteurs et déterminé les réponses cellulaires induites par ce dernier. Nos travaux ont également identifié un potentiel mécanisme d’évasion mise en place par le ZIKV. Nous avons également entrepris un travail original sur un mécanisme moléculaire favorisant la pathogénicité des flavivirus. Une meilleure connaissance de ce mécanisme pourrait déboucher sur l’identification de potentiels cibles thérapeutiques. Enfin, le tropisme neuronal avéré du ZIKV nous a amené à travailler sur la réponse immune des astrocytes humain. En effet, les astrocytes forment une population cellulaire très importante dans le système nerveux central qui est fortement impliquée dans les mécanismes de neurogénèse dans le cerveau des fœtusThe Zika virus (ZIKV) was first isolated from non-human primates the late 1940s. This emerging arbovirus has recently been under the spotlight due to a rapid world pandemic. Belonging to the Flaviviridae family, this flavivirus is transmitted by Aedes’ genus mosquitoes. Historically low pathogenic, a new major concern is the possible association of ZIKV with diverse of neurological complications, including the development of microcephaly and Guillain-Barré syndrome, particularly in newborns of infected mothers. In addition, there is currently no vaccine or specific treatment to cure the disease, so the main preventive measures to fight the spreading of the virus are to prevent mosquitoes’ bites and to plan an effective vector control. A better understanding of the biology of the virus, from the entry in the body, especially at the skin level, to the molecular mechanisms of viral replication, is therefore necessary.Using different molecular and cellular strategies, we investigated the tropism of the virus, identified cell surface receptors and determined the cell’s responses to the infection. Our work also permitted to identify a potential mechanism by which ZIKV evades the host immune system to facilitated his own replication. We also have undertaken original work on a molecular mechanism increasing the pathogenicity of flavivirus. A better knowledge of this mechanism may lead to the identification of potential therapeutic targets. Finally, considering the neuronal tropism of the ZIKV, we studied the immune response of human astrocytes, a very important cell population in the central nervous system, playing a major role in the mechanisms of neurogenesis during the fetus’ brain development
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Ghezali, Grégory. "Control of synaptic transmission by astroglial connexin 30 : molecular basis, activity-dependence and physiological implication." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066423/document.
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Les astrocytes périsynaptiques participent activement, au côté des neurones, dans le traitement de l’information cérébrale. Une propriété essentielle des astrocytes est d’exprimer un niveau élevé de protéines appelées connexines (Cxs), et formant les sous-unités des jonctions communicantes. Étonnamment, bien qu’il ait été suggéré très tôt que la Cx30 astrocytaire soit impliquée dans des processus cognitifs, son rôle exact dans la neurophysiologie demeure cependant encore mal connu. Nous avons récemment révélé que la Cx30, via une fonction non-canal inédite, contrôle la force et la plasticité de la transmission synaptique glutamatergique de l’hippocampe en régulant les niveaux synaptiques de glutamate par le biais du transport astrocytaire du glutamate. Cependant, les mécanismes moléculaire et cellulaire impliqués dans ce contrôle, ainsi que sa régulation dynamique par l’activité neuronale et son impact in vivo dans un contexte physiologique restaient inconnus. Dans le cadre de cette problématique, j’ai démontré durant ma thèse que: 1) La Cx30 induit la maturation morphologique des astrocytes de l’hippocampe par l’intermédiaire de la modulation d’une voie de signalisation dépendante de la laminine et régulant la polarisation cellulaire ; 2) l’expression de la Cx30, sa localisation perisynaptique, ainsi que ses fonctions sont modulées par l’activité neuronale ; 3) Le contrôle de la couverture astrocytaire des synapses du noyau supraoptique de l’hypothalamus par la Cx30 fixe les niveaux plasmatiques de base de la neurohormone ocytocine et ainsi favorise la mise en place de comportements sociaux adaptés. Dans l’ensemble, ces résultats éclairent les régulations des Cxs astrocytaires par l’activité neuronale et leur rôle dans le développement postnatal des réseaux neurogliaux, ainsi que dans le contrôle des interactions structurelles astrocytes-synapses à l’origine de processus comportementauxPerisynaptic astrocytes are active partners of neurons in cerebral information processing. A key property of astrocytes is to express high levels of the gap junction forming proteins, the connexins (Cxs). Strikingly, astroglial Cx30 was suggested early on to be involved in cognitive processes; however, its specific role in neurophysiology has yet been unexplored. We recently reveal that Cx30, through an unconventional non-channel function, controls hippocampal glutamatergic synaptic strength and plasticity by directly setting synaptic glutamate levels through astroglial glutamate clearance. Yet the cellular and molecular mechanisms involved in such control, its dynamic regulation by activity and its impact in vivo in a physiological context were unknown. To answer these questions, I demonstrated during my PhD that: 1) Cx30 drives the morphological maturation of hippocampal astrocytes via the modulation of a laminin signaling pathway regulating cell polarization; 2) Cx30 expression, perisynaptic localization and functions are modulated by neuronal activity; 3) Cx30-mediated control of astrocyte synapse coverage in the supraoptic nucleus of the hypothalamus sets basal plasmatic level of the neurohormone oxytocin and hence promotes appropriate oxytocin-based social abilities. Taken together, these data shed new light on astroglial Cxs activity-dependent regulations and roles in the postnatal development of neuroglial networks, as well as in astrocyte-synapse structural interactions mediating behavioral processes
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Lefevre, Yan. "Rôle de la glie dans la douleur chronique d'origine cancéreuse chez le rat." Thesis, Bordeaux 2, 2013. http://www.theses.fr/2013BOR22090/document.
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Dans le présent travail, le rôle de la glie dans l’expression de la douleur cancéreuse et de la douleur neuropathique a été étudié de façon comparative. Le modèle animal de douleur cancéreuse a été obtenu par injection osseuse dans le tibia, chez la rate Sprague-Dawley, de cellules de carcinome mammaire de type MRMT-1. Le modèle de douleur neuropathique a été obtenu chez le rat Wistar par ligature des nerfs spinaux L5 et L6. Les données obtenues par l’analyse du comportement douloureux en réponse à la stimulation par des filaments de von Frey ont permis de quantifier l’allodynie et l’hyperalgésie mécaniques statiques. La douleur chronique, hors stimulation nociceptive, a été mesurée à l’aide d’un test d’impotence. Les agents pharmacologiques ont été administrés par voie intrapéritonéale ou par voie intrathécale, à l’aide d’un cathéter implanté de façon chronique. L’analyse des comportements nociceptifs après stimulation par filaments de von Frey montre que l’inhibition fonctionnelle transitoire de la glie spinale par le fluorocitrate est sans effet sur la douleur dans les deux modèles. Dans les deux modèles, l’expression des réponses douloureuses dépend de l’activation des récepteurs NMDA spinaux. L’administration par voie intrathécale d’une seule dose de D-aminoacide oxydase, qui dégrade la D-sérine, co-agoniste endogène du récepteur NMDA, réduit l’allodynie et l’hyperalgésie chez les rats neuropathiques et l’allodynie chez les rats cancéreux. Les effets d’un traitement chronique par le fluoroacétate chez les rats neuropathiques sont réversés par l’administration intrathécale de D-sérine. La D-sérine altère légèrement le seuil nociceptif chez les rats cancéreux. Aucun des agents pharmacologiques utilisés ne réverse la réduction d’appui du membre lésé chez les rats cancéreux ou neuropathiques. Ces résultats montrent que, chez le rat, la douleur neuropathique comme la douleur osseuse cancéreuse dépend de la co-activation des récepteurs NMDA spinaux par un de ses ligands endogènes, la D-sérine, mais que seule la douleur neuropathique requiert une glie spinale fonctionnelle. Ils suggèrent donc un rôle différentiel de la glie dans la physiopathologie de ces deux types de douleur chroniqueThe present work has investigated the role of glia upon pain symptoms in a well established peripheral neuropathic pain model and a bone cancer pain model. The neuropathic pain model was obtained by right L5-L6 spinal nerve ligation in male Wistar rats. Bone cancer pain was induced by injecting MRMT-1 rat mammary gland carcinoma cells into the right tibia of Sprague-Dawley female rats. Mechanical allodynia and hyperalgesia were quantified using von Frey hairs and ambulatory incapacitance using dynamic weight bearing. Drugs were administered either acutely or chronically using osmotic pumps, through intrathecal catheters chronically implanted in experimental animals. Using von Frey hair stimuli, we found that transient inhibition of glia metabolism by intrathecal injection of fluorocitrate was ineffective in both models. In both models, pain symptoms required spinal NMDA receptor activation. Intrathecal administration of a single dose of D-aminoacid oxidase, which degrades D-serine, a co-agonist of NMDA receptors, reduced mechanical allodynia and hyperalgesia in neuropathic rats and allodynia in cancer rats. The effect of chronic fluoroacetate in neuropathic rats was reversed by acutely administered intrathecal D-serine, which had only a slight effect in cancer rats. None of these compounds altered the functional disability shown by neuropathic or cancer animals and measured by the dynamic weight bearing apparatus. These results show that neuropathic pain and cancer pains depend upon D-serine co-activation of spinal NMDA receptors but only neuropathic pain requires functional spinal cord glia in the rat. Glia may thus play different roles in the development and maintenance of chronic pain in these two situations
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Ma, Meihui. "Interactions of human immunodeficiency virus type 1 proteins with astrocytes." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq23632.pdf.
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Li, Lizhen. "The role of reactive astrocytes in brain ischemia and neurotrauma /." Göteborg : Institute of Neuroscience and Physiology, Sahlgrenska Academy, Göteborg University, 2006. http://hdl.handle.net/2077/772.
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Sabri, Farideh. "Astrocytes during HIV infection of the brain : relevance for neuropathogenesis /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4536-5/.
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