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The Global ETD Search service is a free service for researchers
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Networked Digital Library of Theses and Dissertations.
Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
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Showing 1 to 3 of 3 (0.116 seconds)| 1 |
Molecular mechanisms of neuronal homoeostasis in vivoSeo, Sang soo January 2016 (has links)
Homeostatic plasticity is important in neurobiology for stabilising neuronal networks in the face of Hebbian forms of synaptic plasticity that are thought to mediate memory storage. Impairment of homeostatic plasticity has also been implicated in neurological diseases such as Rett syndrome and fragile X syndrome. Homeostatic plasticity can be achieved through scaling of the strength of synaptic connections between neurones or by changes in intrinsic excitability. While homeostatic plasticity has been studied mainly using in vitro preparations, it is for the most part not known whether changes of neural activity in vivo induce homeostatic changes. The molecular pathway responsible for homeostatic plasticity still remains unclear. In this thesis, I have used stereotaxic surgery to over express Kir2.1, an inwardly rectifying potassium channel, in vivo in the brains of adult mice. I show that the expression of Kir2.1 through adeno-associated virus (AAV) does not cause any adverse effects in the dentate gyrus nor the CA1 of the mouse hippocampus. I go on to use slice patch clamp methods to measure the change in electrical properties of granule cells in the dentate gyrus and pyramidal cells in CA1 caused by expression of Kir2.1. I show that the excitability of neurones expressing Kir2.1 was reduced compared to control neurones. By 2 weeks after virus injection the neurones showed homeostatic plasticity in response to Kir2.1 over expression. Interestingly, the mechanism of adaptation was different in different types of cells; dentate gyrus granule cells adapted through change in their intrinsic excitability, whereas CA1 pyramidal cells adapted by modifying the strength of their synaptic inputs. To establish whether induction of homeostatic plasticity is associated with changes in gene expression I used fluorescent activated cell sorting (FACs) to isolate pure population of neurones infected with viruses. I then sequenced RNA extracted from neurones expressing Kir2.1 and control neurones. Analysis of the RNAseq data revealed molecular candidates involved in homeostatic plasticity. In summary, I show that Kir2.1 over expression causes change in excitability and subsequent homeostatic plasticity in vivo. The mechanism of adaptation differs between cell types. RNAseq results identify novel candidates for future investigation.
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Les cytokines inflammatoires modulent la prolifération et la différenciation in vitro des cellules souches/progénitrices de la moelle épinièreVaugeois, Alexandre 04 1900 (has links)
No description available.
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SCF cdc4 regulates msn2 and msn4 dependent gene expression to counteract hog1 induced lethalityVendrell Arasa, Alexandre 16 January 2009 (has links)
L'activació sostinguda de Hog1 porta a una inhibició del creixement cel·lular. En aquest treball, hem observat que el fenotip de letalitat causat per l'activació sostinguda de Hog1 és parcialment inhibida per la mutació del complexe SCFCDC4. La inhibició de la mort causada per l'activació sostinguda de Hog1 depèn de la via d'extensió de la vida. Quan Hog1 s'activa de manera sostinguda, la mutació al complexe SCFCDC4 fa que augmenti l'expressió gènica depenent de Msn2 i Msn4 que condueix a una sobreexpressió del gen PNC1 i a una hiperactivació de la deacetilassa Sir2. La hiperactivació de Sir2 és capaç d'inhibir la mort causada per l'activació sostinguda de Hog1. També hem observat que la mort cel·lular causada per l'activació sostinguda de Hog1 és deguda a una inducció d'apoptosi. L'apoptosi induïda per Hog1 és inhibida per la mutació al complexe SCFCDC4. Per tant, la via d'extensió de la vida és capaç de prevenir l'apoptosi a través d'un mecanisme desconegut. / Sustained Hog1 activation leads to an inhibition of cell growth. In this work, we have observed that the lethal phenotype caused by sustained Hog1 activation is prevented by SCFCDC4 mutants. The prevention of Hog1-induced cell death by SCFCDC4 mutation depends on the lifespan extension pathway. Upon sustained Hog1 activation, SCFCDC4 mutation increases Msn2 and Msn4 dependent gene expression that leads to a PNC1 overexpression and a Sir2 deacetylase hyperactivation. Then, hyperactivation of Sir2 is able to prevent cell death caused by sustained Hog1 activation. We have also observed that cell death upon sustained Hog1 activation is due to an induction of apoptosis. The apoptosis induced by Hog1 is decreased by SCFCDC4 mutation. Therefore, lifespan extension pathway is able to prevent apoptosis by an unknown mechanism.
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