Дисертації з теми "Rett syndrome MeCP2"
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Sampathkumar, Charanya [Verfasser]. "Interplay between MeCP2 and BDNF in Rett Syndrome / Charanya Sampathkumar." Berlin : Freie Universität Berlin, 2017. http://d-nb.info/1123572259/34.
Повний текст джерелаShah, Ruth Rama. "Human neuronal LUHMES cell line as a model system for studying Rett syndrome." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31396.
Повний текст джерелаKriaucinonis, S. "Study of MeCP2 function in a mouse model of Rett syndrome." Thesis, University of Edinburgh, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.653565.
Повний текст джерелаKriaucionis, Skirmantas. "Study of MeCP2 function in a mouse model for Rett syndrome." Thesis, University of Edinburgh, 2004. http://hdl.handle.net/1842/11013.
Повний текст джерелаPetazzi, Paolo. "Methyl-CpG binding protein 2 deregulation: from Rett syndrome to MeCP2 duplication disorder." Doctoral thesis, Universitat de Barcelona, 2015. http://hdl.handle.net/10803/396242.
Повний текст джерелаIntroducción: El síndrome de Rett (RTT, OMIM#312750) fue por primera vez descrito en 1966 por el pediatra austriaco Andreas Rett. El síndrome de Rett causa retraso mental en 1 de cada 10000 niñas, lo que hace que sea la segunda causa de retraso mental en niñas. En 1999 en el laboratorio de Huda Zoghbi descubrieron las bases genéticas de la enfermedad. El 95% de los casos de Rett clásico se produce por mutaciones en MeCP2. Es interesante el hecho de que mutaciones que provocan el incremento de copias del gen MECP2 también llevan a enfermedades neurológicas, como es el caso del trastorno provocado por la duplicación de MeCP2. MeCP2 es una proteína nuclear, que se expresa en diferentes tejidos, pero es especialmente abundante en neuronas del sistema nervioso maduro. MeCP2 es una proteína con capacidad para unirse a dinucleótidos CpG. Entre las varias funciones biológicas propuesta para MeCP2 se encuentran: 1) Silenciamento transcripcional; 2) activador transcripcional; 3) regulador de splicing; 4) Regulador de la cromatina. Objetivos del estudio: El principal objetivo de esta tesis es evaluar el impacto del incremento o disminución de expresión de MeCP2 , tanto a nivel transcripcional como de desarrollo, al fin de caracterizar las vías moleculares desreguladas en las manifestaciones clínicas relacionadas con MeCP2. En los primeros dos estudios se buscarán nuevos targets de MeCP2 a través de dos diferentes tecnologías, secuenciación del ARN y microarray. En ambos estudios utilizaremos un modelo murino bien establecido (MeCP2-null), obtenido mediante supresión del gen MeCP2, que simula el síndrome de Rett. Las diferencias entre los primeros dos estudios es que mientras en el primero se buscarán solo "long non-coding RNA" relacionados con MeCP2, el segundo será enfocado en todos los ARN codificantes. En el tercer estudio evaluaremos el efecto de la sobreexpresión de MeCP2 en un bien establecido modelo de desarrollo embrionario como es el embrión de pollo. Resultados y conclusiones: Parte 1 * Se han encontrado 701 lncRNAs diferencialmente expresados entre el cerebro del ratón Mecp2-null y el control (salvaje). * MeCP2 está unido a los promotores de los lncRNAs AK081227 y AK087060. * El incremento de expresión de AK081227 en ratones Mecp2-null está asociado con la bajada de expresión de su gen huésped Gabrr2 en cuatro regiones del cerebro. * La sobre regulación de AK087060 se correlaciona con un aumento en la expresión de su gen huésped Arhgef26 en las cuatro regiones cerebrales estudiadas. Parte 2 * Hemos encontrados 1049 y 1154 transcritos diferencialmente expresado en el hipocampo (HIP) y la corteza pre-frontal (PFC), respectivamente, del ratón Mecp2- null. * Los genes "immediate early genes" (IEGs) Fos, JunB, EGR2, NR4A1, Npas4, FosB y Egrl están sobreexpresados en el HIP de Mecp2-null. Además, Fos, JunB, Npas4 y FosB están sobreexpresados también en el PFC. * En tanto la PFC como en el HIP del ratón wild-type, la unión de MeCP2 se reduce en las regiones asociadas con alto contenido de CpG de los genes Fos, JunB, NR4A1, Npas4, FosB y Egr1. Además, los promotores de Fos, JunB y Npas4 son más accesibles a la digestión con nucleasas micrococales (MNase) en el HIP de ratones Mecp2-null. * Cuatro IEGs (Fos, JunB, Egr2, Npas4) muestran un patrón de expresión alterado en neuronas derivadas de animales Mecp2-null y tratadas con forskolina. * La expresión de JunB es incrementada significativamente en el hipocampo de los animales Mecp2-null tratados con ácido kaínico, en comparación con ratones controles tratados. Parte 3 * El transcrito y la proteína de MeCP2 de pollo se expresan en varios estadio del desarrollo embrionario y especialmente en el tubo neural * La sobreexpresión de MeCP2 en el tubo neural de embriones de pollo provoca una disminución general en el número de células proliferantes. Además, el patrón de localización del marcador mitótico H3S1Op es aberrante en tubos neurales que sobreexpresan MeCP2. * Una dosis elevada de MeCP2 provoca una clara disminución de las neuronas diferenciadas localizadas en la zona del mantel. Por otra parte, la sobreexpresión de MeCP2 conduce a una disminución del marcador de polaridad neuroepitelia Ncadherin. * La sobreexpresión de MeCP2 en tubos neurales provoca un aumento de apoptosis.
Ekiert, Robert. "Analysis of partner proteins of MeCP2 and their relevance to Rett syndrome." Thesis, University of Edinburgh, 2012. http://hdl.handle.net/1842/9901.
Повний текст джерелаSkene, Peter J. "Global analysis of the methyl-CpG binding protein MeCP2." Thesis, University of Edinburgh, 2010. http://hdl.handle.net/1842/4737.
Повний текст джерелаWhite, Darren Andrew. "Mutations of MeCP2 disrupt the association with deacetylase complexes : implications for Rett syndrome." Thesis, University of Birmingham, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.403942.
Повний текст джерелаKruusvee, Valdeko. "The structural basis of MeCP2 interaction with NCoR/SMRT co-repressor complex." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/25703.
Повний текст джерелаEhinger, Yann. "Stratégies de stimulation du transport axonal endogène du Bdnf comme piste thérapeutique dans le syndrome de Rett." Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0142/document.
Повний текст джерелаRett syndrome (RTT) is a severe neurological disorder caused by mutations in the MECP2 gene, located on the X chromosome. After a period of apparent normal development, females with MECP2 mutations undergo a regression of early developmental milestones, resulting in the deterioration of motor skills, eye contact, speech, and hand movements and ultimately resulting in severe breathing disturbances, as the disease progresses, and severe handicap. Bdnf, a neuronal modulator that plays a key role in neuronal survival, development, and plasticity has been found to be one of the main factors altered in the absence of Mecp2. The Bdnf pathway is one of the most appealing pathways to target in RTT. Bdnf itself is unable to cross the blood-brain barrier (BBB) and needs to be indirectly activated. Thus, we developed an indirect strategy to enhance Bdnf trafficking in neurons. Huntingtin (Htt) phosphorylation of Serine 421 enhances Bdnf transport and promoting Htt phosphorylation may restore Bdnf homeostasis in Mecp2 KO brain. We tested this possibility using two approaches to promote Htt phosphorylation of S421 in Mecp2-deficient neurons and Mecp2 KO mice. We evaluated the consequences of Htt S421 phosphorylation on BDNF axonal trafficking in projecting corticostriatal neurons in vitro, and in vivo on the behavior of Mecp2 KO mice. Our findings demonstrate that pharmacological and genetic stimulation approaches correct Bdnf trafficking in vitro and improve longevity and behavioural features in Mecp2 KO mice. Htt S421 phosphorylation appears to be a possible target for the development of treatments in RTT
SORMONTA, IRENE. "Svilluppo di un nuovo sistema di drug screening cellulare e molecolare per il trattamento della sindrome di Rett." Doctoral thesis, Università Vita-Salute San Raffaele, 2023. https://hdl.handle.net/20.500.11768/136977.
Повний текст джерелаAbstract Rett syndrome (RTT) is a devastating neurodevelopmental disorder caused by mutations in the X-linked MECP2 gene, primarily acting as transcriptional repressor. Although RTT proved to be reversible in mice, no cure is yet available. Several Mecp2-muntant mouse models have been developed and they generally reproduce behavioral and physiological phenotypes observed in RTT patients, establishing that disease phenotypes are widely due to neuronal dysfunctions. However, their use in large drug screening programs require a great number of animals, elevated costs and time-consuming experimental approaches. To support the in vivo evaluation, new drug screening systems have emerged in vitro, usually based on the analysis of neuronal defective morphology. We previously demonstrated that the amelioration of the transcriptional profile in Mecp2-null neurons appears as a better indicator of functional rescue than morphological readouts. For this reason, we aimed at developing a cell-based drug screening system for RTT therapy, based on customized high-throughput 96x96 qRT-PCR arrays. To this purpose, a longitudinal RNASeq analysis performed in differentiating Mecp2-null neuronal precursors cells identified consistent transcriptional defects of RTT neurons. By using different prioritization criteria and testing selected neuronal differentially expressed genes (DEGs) on 96x96 qRT-PCR cards, we established a group of reproducible DEGs which represent our quantitative probes to measure the transcriptional amelioration induced by the drugs tested. To assess whether the selected DEGs are able to reflect the efficacy of drugs in vivo, we analyzed the effects of the ampakine CX546, for which we previously published positive results in vitro and in vivo. The drug demonstrated to rescue 75% of our selected DEGs, though a sample size larger than expected was required to reproduce RNASeq data in qRT-PCR experiments, forcing us to reconsider its use for the screening of large drug libraries in a laboratory scale. Thus, we propose the use of our screening system as either a confirmatory approach of a previously produced selection of molecules or as a useful system to validate rationally deduced pharmacological approaches. As secondary outcome, we identified and further characterized a consistent defect in the expression of two genes, Haus7 and Nsdhl, in cultured neurons and Mecp2-defective tissues, prompting further investigations of their role and functions in RTT pathogenesis. A comprehensive analysis of their expression across different stages and models of the disorder lay the foundation for novel possible pathogenic mechanisms of RTT and hopefully will provide new potential targets for RTT therapy.
O'Connor, Rose Deeter. "MeCP2 deficiency decreases bone formation and reduces bone volume in a rodent model of Rett syndrome." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 161 p, 2009. http://proquest.umi.com/pqdweb?did=1891570941&sid=6&Fmt=2&clientId=8331&RQT=309&VName=PQD.
Повний текст джерелаPowers, Samantha Lynn. "Advancing Treatment and Understanding of Rett Syndrome." The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1586786333743142.
Повний текст джерелаGadalla, Kamal Kamal El-Sayed. "Virus-mediated delivery of MECP2 as a potential tool for the treatment of Rett syndrome." Thesis, University of Glasgow, 2012. http://theses.gla.ac.uk/3501/.
Повний текст джерелаSantos, Mónica Joana Pinto dos. "Pathogenesis of Rett syndrome and study of the role of meCP2 protein in neuronal function." Doctoral thesis, Instituto de Ciências Biomédicas Abel Salazar, 2007. http://hdl.handle.net/10216/7217.
Повний текст джерелаWilliamson, Sarah Louise. "Methyl CpG binding protein 2 (MeCP2), cyclin dependent kinase like 5 (CDKL5) and Rett syndrome." Thesis, The University of Sydney, 2007. https://hdl.handle.net/2123/28077.
Повний текст джерелаSantos, Mónica Joana Pinto dos. "Pathogenesis of Rett syndrome and study of the role of meCP2 protein in neuronal function." Tese, Instituto de Ciências Biomédicas Abel Salazar, 2007. http://hdl.handle.net/10216/7217.
Повний текст джерелаPanayotis, Nicolas. "Etude des déficits catécholaminergiques centraux chez la souris Mecp2-déficiente, modèle murin du syndrome de Rett." Thesis, Aix-Marseille 2, 2011. http://www.theses.fr/2011AIX20734.
Повний текст джерелаDNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. The protein Mecp2 (Methyl CpG binding protein 2), encoded by a gene located on the X chromosome, belongs to the ‘Methyl Binding domain’ protein family. Based on its structure and its interactions Mecp2 has historically been described as a repressor of expression for many genes. Currently, its involvement as an activator of transcription and its role in chromatin architecture suggests that it could be a global regulator of the epigenome. Mutations in MECP2 lead to neurological disorders, among which Rett syndrome (RTT). This dominant X-linked pathology mainly affects girls (incidence: 1/15000 live births). Although the precise causes of the RTT phenotype are unknown, the pattern of Mecp2 expression is related to synaptogenesis, maturation and neuromaintenance. Before my integration in the ‘Human Neurogenetics’ team, this group identified neural deficits, affecting brainstem and peripheral catecholaminergic cell groups, causing respiratory disturbances in a mouse model of this disease. My thesis work enabled the characterization of the postnatal physiological and motor deficits affecting the Mecp2-deficient mice. The study of catecholaminergic structures of interest such as the substantia nigra pars compacta and the locus coeruleus has revealed that the central noradrenergic and dopaminergic neurons are affected in their metabolism. The number of immunolabelled neurons of these groups appears significantly reduced and would result in a gradual loss of the mature ‘catecholaminergic’ phenotype, in the absence of cell death. Our data suggest that these defects are a neuropathological correlate for behavioral disorders observed in Mecp2-deficient mice. Some motor deficits have been improved, with L-Dopa, a pro-dopaminergic drug. In relation with Bdnf (Brain-derived neurotrophic factor) reduction described in patients and Mecp2-deficient mice, we identified that a change in the dosage of Mecp2 deregulates genes (Htt, Hap1) encoding proteins involved in the intracellular transport of Bdnf. Our work allows to postulate that in the Mecp2-deficient neurons, an altered dynamics of Bdnf vesicles transport could exacerbate the deficit of expression of this neurotrophin. Our treatment of Mecp2-deficient mice with cysteamine, a molecule able to increase Bdnf contents and enhancing its release and secretion, increased the survival of the animals and reduced their motor defects. Our results show that the Mecp2-deficiencies lead to alteration in the axonal transport of Bdnf in addition to deficits in Bdnf production. In addition, by the use of pharmacological agents that affect this transport, we offer new therapeutic perspectives
Kaddoum, Lara. "La protéine MeCP2 : étude de son implication dans la réponse aux dommages à l'ADN et développement de nouveaux outils pour sa détection." Toulouse 3, 2010. http://thesesups.ups-tlse.fr/1683/.
Повний текст джерелаRett syndrome is a severe and progressive X-linked neurodevelopmental disorder that affects 1/10000 female birth. RTT is caused by mutations in the mecp2 gene, encoding the Methyl CpG binding Protein 2. MeCP2 binds to methylated DNA and has several roles in: transcription activation or repression, chromatin remodeling, alternative splicing of mRNA. . . Initially, my thesis project was to explore the hypothesis that MeCP2 may be able to transfer between cells. My results suggest that this phenomenon appears after cell fixation with acetone and doesn't occur in vivo. This work, however, allowed us to develop a new staining method to detect and localize proteins in mammalian cells using the split-GFP system. Within the frame of this project, I have also produced antibodies specific for each of the two MeCP2 isoforms. These novel antibodies should prove to be interesting tools to understand the role of each isoform in the pathology of Rett syndrome. More recently, my work was focalized on the relationship between MeCP2 and DNA damage. I was able to show that MeCP2 accumulates on DNA damage. Future work will be aimed at understanding the mechanisms involved in this newly uncovered function of MeCP2, and will hopefully improve our understanding of Rett syndrome pathogenesis
Bittolo, Tamara. "Pharmacological approches for the treatment of the Rett syndrome." Doctoral thesis, Università degli studi di Trieste, 2014. http://hdl.handle.net/10077/10258.
Повний текст джерелаRIASSUNTO La syndrome di Rett (RTT) è una patologia dello sviluppo neuronale postnatale causata dalle mutazioni del gene MeCP2, situato nel cromosoma X, codificante per la Methyl CpG binding protein 2, un modulatore della trascrizione. La forma classica si manifesta in 1:10,000 bambine ed è caratterizzata da una progressiva regressione generale fisica e mentale, in seguito ad un normale sviluppo nei primi 2 anni di vita. Molti degli aspetti della patologia sono stati riprodotti in diversi modelli murini deleti per il gene MeCP2 (MeCP2-/y), inclusi la riduzione della massa cerebrale, l’atrofia neuronale e le disfunzioni cardiorespiratorie, che costituiscono i parametri più robusti e riproducibili tra i diversi modelli murini, accanto ai meno conservati parametri comportamentali, come l’ansia, la socievolezza e l’aspetto motorio. Il fenotipo Rett è caratterizzato inoltre da una riduzione dei livelli di espressione della serotonina (5HT), norepinefrina (NE) e del BDNF (Brain Derived Neurotrophic Factor). Tuttavia, è noto che i farmaci antidepressivi sono in grado di modulare i livelli di BDNF in parte regolando il sistema monoaminergico. Lo scopo di questo lavoro consiste perciò nel valutare gli effetti del trattamento cronico con antidepressivi in un modello della sindrome di Rett. Abbiamo scelto la Desipramina (DMI) come farmaco di controllo, dal momento che è già stata precedentemente utilizzata per un trial clinico della sindrome di Rett. La Desipramina è un antidepressivo che blocca il recupero di 5HT e NE a livello dello spazio sinaptico, tuttavia presenta delle complicanze cliniche a livello cardiaco. Per evitare tale effetto collaterale della DMI, abbiamo selezionato un antidepressivo altamente tollerabile, la Mirtazapina (MIR), un antagonista degli α2 autorecettori ed eterorecettori centrali e uno specifico inibitore dei recettori 5HT2 e 5HT3. Il lavoro si divide in 4 fasi: Fase 1: analisi degli effetti del trattamento con antidepressivi sul peso del corpo e del cervello ed analisi della morfologia dei neuroni piramidali della corteccia somatosensoriale in un modello murino della sindrome di Rett Fase 2: analisi degli effetti del trattamento con antidepressivi sui parametri vitali, inclusi il battito cardiaco e la frequenza respiratoria nel modello murino della sindrome di Rett Fase 3: analisi degli effetti del trattamento con antidepressivi sul comportamento nel modello murino della sindrome di Rett Fase 4: analisi degli effetti del trattamento con antidepressivi sul livello di espressione del BDNF Fase 1: analisi degli effetti del trattamento con antidepressivi sul peso del corpo e del cervello ed analisi della morfologia dei neuroni piramidali della corteccia somatosensoriale in un modello murino della sindrome di Rett Prima di tutto abbiamo valutato le caratteristiche generali del modello murino della sindrome di Rett (MeCP2-/y), osservando che il peso del corpo e del cervello dell’animale era significativamente ridotto a 42 giorni dalla nascita. Inoltre, come osservato in precedenza (Kishi and Macklis, 2004, Fukuda et al., 2005), abbiamo confermato la significativa riduzione dello spessore totale della corteccia somatosensoriale (la più compromessa in questa patologia), in particolare degli strati II-III e VI a 42 giorni dalla nascita. Abbiamo quindi trattato gli animali per due settimane a partire dal 28° giorno dalla nascita con DMI alla concentrazione 10 mg/Kg e con MIR a due differenti concentrazioni (10 o 50 mg/Kg) ed analizzato gli effetti del trattamento sul peso del corpo e del cervello. Non abbiamo riscontrato differenze per quanto riguarda il peso del corpo dopo trattamento farmacologico, tuttavia abbiamo notato un significativo aumento del peso del cervello in topi MeCP2-/y dopo 2 settimane di trattamento con MIR 50 mg/Kg, confrontato con il peso del cervello di topi MeCP2-/y della stessa età non trattati. Per meglio definire le strutture coinvolte nel recupero del peso cerebrale dopo trattamento con MIR 50 mg/Kg, abbiamo effettuato una colorazione Nissl su sezioni coronali di cervello di topo e abbiamo analizzato l’ippocampo e la corteccia somatosensoriale. Abbiamo osservato che non c’erano differenze nelle proporzioni di ogni strato ippocampale rispetto allo spessore totale dell’ippocampo lungo l’asse rostro-caudale. Tuttavia, l’analisi della corteccia somatosensoriale ha rivelato che il trattamento con DMI 10 mg/Kg e MIR 50 mg/Kg fa recuperare lo spessore totale della corteccia in topi MeCP2-/y a 42 giorni dalla nascita ed in particolare lo spessore degli strati II-III e VI che sono principalmente compromessi nel modello murino della sindrome di Rett (Kishi and Macklis, 2004, Fukuda et al., 2005). Per avere maggiori informazioni sull’effetto della MIR 50 mg/Kg a livello dei neuroni corticali, abbiamo esaminato la morfologia dei neuroni piramidali dello strato II-III della corteccia somatosensoriale in topi MeCP2-/y a 42 giorni dalla nascita utilizzando la colorazione di Golgi. Abbiamo osservato che il trattamento con MIR 50 mg/Kg induce un recupero dei deficit morfologici presenti nel modello murino (Kishi and Macklis, 2004, Fukuda et al., 2005) inclusi, la ridotta area del soma, il diametro ridotto dei dendriti apicali, l’atrofia dell’albero dendritico apicale ed in particolare quello basale, il numero delle spine “stubby” sia nei dendriti secondari apicali che basali. Infine, dal momento che è stato precedentemento osservato un deficit di rilascio del GABA in topi MeCP2-/y (Chao et al., 2010), abbiamo deciso di valutare se la MIR 50 mg/Kg era in grado di recuperare questo deficit. Abbiamo quindi dimostrato che le correnti GABA sono parzialmente recuperate dopo trattamento con MIR 50 mg/Kg nella corteccia di topi MeCP2-/y a 42 giorni dalla nascita. Fase 2: analisi degli effetti del trattamento con antidepressivi sui parametri vitali, inclusi il battito cardiaco e la frequenza respiratoria nel modello murino della sindrome di Rett I pazienti Rett e i topi MeCP2-/y presentano alterazioni cardiache e un respiro anomalo allo stato avanzato della patologia. Attraverso uno strumento non invasivo (MouseOX), abbiamo raccolto i dati relativi alla saturazione dell’ossigeno (percentuale di siti dell’emoglobina occupati dalle molecole di ossigeno), il battito cardiaco e la frequenza respiratoria (numero di battiti e respiri al minuto) e la distensione dell’arteria in base al battito cardiaco in topi Wild Type e MeCP2-/y non trattati e trattati con DMI 10 mg/Kg or MIR 50 mg/Kg. Abbiamo osservato che non ci sono alterazioni nella saturazione dell’ossigeno, tuttavia la frequenza dei battiti cardiaci e del respiro, che è ridotta nei topi MeCP2-/y non trattati, viene recuperata in seguito a trattamento con gli antidepressivi, in particolare con la MIR. Inoltre, l’effetto negativo sulla distensione dell’arteria osservato per la DMI 10 mg/Kg, non viene alterato dal trattamento con MIR 50 mg/Kg. Fase 3: analisi degli effetti del trattamento con antidepressivi sul comportamento nel modello murino della sindrome di Rett I topi MeCP2-/y sono caratterizzati dal disturbi motori e una ridotta ansia (Chahrour and Zoghbi, 2007), cosi abbiamo deciso di testare gli effetti degli antidepressivi sul comportamento del modello murino della sindrome di Rett. Attraverso il test dell’”open field”, abbiamo dimostrato che i topi MeCP2-/y trattati con i farmaci trascorrono la maggior parte del tempo del test immobili, e la loro attività in termini di capacità di alzarsi e tenersi sulle zampe posteriori e di cura personale è ridotta. Queste osservazioni sono probabilmente dovute all’effetto sedativo indotto dal trattamento con antidepressivi. Tuttavia, l’ansia che è ridotta nei topi MeCP2-/y non trattati osservata nel test dell’”elevated plus maze”, ritorna a valori normali dopo trattamento con gli antidepressivi. Fase 4: analisi degli effetti del trattamento con antidepressivi sul livello di espressione del BDNF Precedenti studi hanno dimostrato che il livello di espressione del BDNF totale è significativamente ridotto nel cervello dei topi MeCP2-/y (Chang et al., 2006, Wang et al., 2006). In questo lavoro abbiamo dapprima dimostrato come i livelli delle diverse isoforme del BDNF variano sulla base della mutazione del gene MeCP2 nei pazienti Rett. Successivamente abbiamo valutato le diverse isoforme del BDNF nel prosencefalo di topi MeCP2-/y dimostrando come esse siano significativamente ridotte a 42 giorni dalla nascita. Tuttavia, il trattamento con DMI 10 mg/Kg e MIR 50 mg/Kg non è in grado di recuperare in modo significativo il livello di mRNA. Abbiamo quindi valutato il livello proteico del BDNF, dimostrando un aumento della neurotrofina a livello corticale e una diminuzione a livello ippocampale in topi MeCP2-/y non trattati ma non statisticamente significativo. Tuttavia il trattamento con MIR 50 mg/Kg sembra recuperare il livello del BDNF, sebbene non sia significativo.
ABSTRACT Rett syndrome (RTT) is an X-linked postnatal neurodevelopmental disorder caused by the mutations on MeCP2 gene which encodes for the Methyl CpG binding protein 2, a transcriptional regulator. The classical form manifests in girls with an incidence of 1:10,000 with a progressive general physical and mental regression after a normal development during the first two years of age. Several clinical features are recapitulated in MeCP2-/y mice, including the reduced brain mass, neuronal atrophy and the cardiorespiratory abnormalities, which are considered the most robust and reproducible parameters among the Rett mouse models and the less conserved alterations on mice behavior. Rett phenotype was characterized by a reduction on serotonin, norepinephrine (5HT; NE) and BDNF (Brain Derived Neurotrophic Factor) expression level. However, it is known that the antidepressants drugs modulate BDNF expression level partly by regulation of monoamine systems. The aim of the project is to evaluate the effects of repeated antidepressant treatments in a Rett mouse model. We choose Desipramine (DMI) as control drug because it was previously used in a clinical trial of Rett syndrome. DMI blocks the reuptake of 5HT and NE, but it has some cardiac complications. To overcame the cardiac side effect of DMI, we selected the highly tolerable antidepressant Mirtazapine (MIR), which is an antagonist of central α2 autoreceptors and α2 heteroreceptors and a specific blocker of 5HT2 and 5HT3 receptors. The project comprises four phases: Phase1: Analysis of the effects of antidepressant treatments on body and brain weight, including the morphology of the somatosensory pyramidal neurons in a model of Rett syndrome (MeCP2-/y) Phase2: Analysis of the effects of antidepressant treatments on the vital signs parameters, including heart and breath rate in MeCP2-/y mice Phase3: Analysis of the effects of antidepressant treatments on the behavior of the mice (open field and plus maze test) in MeCP2-/y mice Phase4: Analysis of the effects of antidepressant treatments on brain derived neurotrophic factor (BDNF) expression level Phase1: Analysis of the effects of the drugs on body and brain weight, including the morphology of the somatosensory pyramidal neurons in a model of Rett syndrome (MeCP2-/y) First of all, we evaluated the general features of the Rett mouse model, observing that the body and the brain weight of MeCP2-/y mice were reduced at postnatal day 42 (p42). We found also that there is a significant reduction on total cortical thickness, in particular of layers II-III and VI at p42 as observed in previous studies (Kishi and Macklis, 2004, Fukuda et al., 2005). Then, we analyzed the effects of DMI 10 mg/Kg and MIR (at two different concentration: 10 or 50 mg/Kg) treatments on body and brain weight. No difference was observed for body weight, while an increase in brain weight was noticed after treatment with MIR 50 mg/Kg in p42 MeCP2-/y mice compared to MeCP2-/y untreated mice. To better define the brain structures involved in the rescue of the brain weight after MIR 50 mg/Kg treatment, we performed a Nissl staining and we analyzed the hippocampus and the somatosensory cortex. We found that among p42 MeCP2-/y treated mice, there were no differences in the proportion of each hippocampal layer to the total thickness along the rostro-caudal axis. However, the analysis of the somatosensory cortex revealed that DMI 10 mg/Kg and MIR 50 mg/Kg rescued the total cortical thickness in p42 MeCP2-/y mice and in particular the layers II-III and VI which are principally compromised in Rett mouse model (Kishi and Macklis, 2004, Fukuda et al., 2005). To gain further insight regarding the effect of Mirtazapine treatment on cortical neurons, we investigated the morphology of layer II-III pyramidal neurons of the somatosensory cortex in MeCP2-/y mice using Golgi staining. We observed that MIR 50 mg/Kg treatment was able to recover the neuronal morphology deficits of p42 MeCP2-/y mice (Kishi and Macklis, 2004, Fukuda et al., 2005), including, the small soma area, the reduced diameter of apical dendrites, the atrophy of apical and, in particular, the basal dendritic arborization, the number of secondary basal dendrites, the number of stubby spines both in secondary apical and basal dendrites. Finally, as a deficit on GABA release in MeCP2-/y mice was previously described (Chao et al., 2010), we investigatd if Mirtazapine could rescue this deficit. Indeed, we found that GABA currents were rescued by MIR 50 mg/Kg treatment in the cortex of p42 MeCP2-/y mice, although without reaching full recovery. Phase2: Analysis of the effects of the drugs on the vital signs parameters, including heart and breath rate in MeCP2-/y mice Rett patients and MeCP2-/y mice presents cardiac alterations and breathing abnormalities in a later stage of the disorder. Through a non-invasive instrument (MouseOX) we collected the data regarding the Oxygen Saturation (percentage of sites of arterial hemoglobin occupied by oxygen molecules), the Hearth and the Breath Rate (number of beats or breaths per minute) and the Pulse Distention (change in distension of the arterial blood vessels due to a cardiac pulse) on Wild Type and MeCP2-/y mice untreated or treated with DMI 10 mg/Kg or MIR 50 mg/Kg. We found that no alterations was observed for the oxygen saturation, however the frequency of heart and breath are rescued after drug treatments. A negative effect of Desipramine was observed in pulse distention which is not affected with Mirtazapine treatment. Phase3: Analysis of the effects of the drugs on the behavior of the mice (open field and plus maze test) MeCP2-/y mice are characterized by motor abnormalities and a decreased anxiety (Chahrour and Zoghbi, 2007), thus, we tested the effects of the antidepressant drugs on the behavior of MeCP2-/y mice. Through an open field test, we found that the MeCP2-/y mice treated with the drugs spent more of the time immobile, and their activity in terms of number of rearing and grooming was reduced. These observations are probably due to the sedative effect of antidepressant treatments. However, the anxiety was recover to normal levels in MeCP2-/y mice treated with the antidepressants in the elevated plus maze. Phase4: Analysis of the effects of treatments on BDNF expression level Previous studies showed that total BDNF expression level was significantly reduced in the brain of MeCP2-/y mice (Chang et al., 2006, Wang et al., 2006). First of all, we demonstrated that the levels of BDNF isoforms depend on mutations in MeCP2 gene in Rett patients. Then, we evaluated the BDNF splice variants in the forebrain of MeCP2-/y mice and we demonstrated that they were significantly reduced at p42. However, treatments with DMI 10 mg/Kg or MIR 50 mg/Kg not rescue significantly the mRNA of BDNF. Therefore, we evaluated the protein level of BDNF and we demonstrated a no statistically significant increase of the neurotrophin in the cortex and a decrease in the hippocampus in MeCP2-/y untreated mice. However, the treatment with MIR 50 mg/Kg seemed to rescue the protein level of BDNF, even if no statistically significant.
XXVI Ciclo
1985
Miralvès, Julie. "Exploration des rôles immuno-modulateurs de MeCP2 et de son transfert intercellulaire." Toulouse 3, 2007. http://thesesups.ups-tlse.fr/39/.
Повний текст джерелаMutations in the X-linked MECP2 gene are the cause of the Rett Syndrome (RTT), a progressive neurodevelopmental disorder leading to important neurological deficiencies, including motor, vegetative and cognitive dysfunctions. To date, despite the identification of MECP2 mutations as the central cause for RTT and the generation of several mouse models mimicking the human disease, the molecular basis for the pathogenesis of the syndrome still remains to be clearly elucidated. MeCP2 (Methyl-CpG-binding protein 2) has been shown to harbour a transcriptional repression activity by its ability to bind methylated CpG nucleotides and to recruit co-repressor complexes. Moreover, MeCP2 is involved in RNA splicing regulation of target genes, takes part in the chromatin architecture and can also associate with Dnmt1, the maintenance DNA methyl-transferase. MeCP2 is therefore a multifunctional protein that is involved at many levels of genes' regulation. MHC class I molecules, whose genes are particularly rich in CpG islands, are required in the brain for the establishment and maintenance of neuronal connections during development, in plastic remodelling in the hippocampus and in neuronal signalling in specific brain areas. .
Couvert, Philippe. "Physiopathologie moléculaire des retards mentaux syndromiques et non spécifiques liés à des mutations du gène MECP2." Paris 5, 2002. http://www.theses.fr/2002PA05CD07.
Повний текст джерелаChapleau, Christopher Allen. "The developmental functions of BDNF and MECP2 on dendritic and synaptic structure." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2008. https://www.mhsl.uab.edu/dt/2008p/chapleau.pdf.
Повний текст джерелаVaghi, Valentina. "BDNF translational control as a therapeutic target in Rett syndorme." Doctoral thesis, Università degli studi di Trieste, 2011. http://hdl.handle.net/10077/5434.
Повний текст джерелаRett syndrome (RTT, MIM 312750) is a debilitating neurodevelopmental disorder that manifests in early childhood and affects almost exclusively girls. It 's a genetic disorder and is present worldwide with an estimated average incidence of 1:10,000 / 15,000 newborn girls. RTT is the second leading cause of mental retardation in female often misdiagnosed as autism or an unspecified developmental delay. In its classic version, this disease is caused by mutations in the transcription factor Methyl-CpG binding protein 2 (MeCP2) located on the female X chromosome (Amir et al., 1999). MeCP2 is a transcriptional regulator of many genes, including the neurotrophic factor Brain Derived Neurotrophic Factor (BDNF). BDNF is a member of the neurotrophins family and represents a key molecule for neuronal survival and development, and it is involved in learning and memory processes. BDNF levels significantly increase during the first period of postnatal life till it reaches the threshold necessary for the maturations of neurons with the development of dendrites, axons, dendritic spines and synapses. Recent studies have shown that in transgenic mice, in which MECP2 gene has been inactivated to mimic the symptoms of RTT, the mRNA levels of BDNF are reduced and, in these animals at 6-8 weeks of age, the total content of BDNF protein is reduced by 70%. Furthermore, the overexpression of BDNF in MeCP2-/Y mice leads to an increase in lifespan, improved locomotor deficits and electrophysiological defects, while the deletion of the gene coding for BDNF in the same animals leads to an early onset of the disease symptoms. The main goal of this thesis is to identify a possible drug treatment for the treatment of RTT. The idea is based on the fact that in animal models of RTT there are residual levels of mRNA coding for BDNF and that many drugs, mostly used for the treatment of depression, are able to increase the synthesis of BDNF. In this study we analyzed the residual expression of different BDNF transcripts in human brain and in two models of RTT (the mouse and the cellular model). Using quantitative PCR, we determined the residual expression of BDNF transcripts in post mortem brain samples of RTT patients, using tissues from somatosensory and motor cortex (Broadmann areas 1-5), which are the most affected by the disease. In addition, we determined the expression of BDNF transcripts in the cortex and hippocampus of MeCP2-/Y at different of post-natal ages. Finally, in order to establish a cellular model of disease, we disrupted the expression of MeCP2 gene in human neuroblastoma cell line SHSY-5Y (via RNA interference), and then we measured the expression levels of BDNF transcripts. Using the same cell line we obtained information on the translatability of the different BDNF transcripts through a luminescence assay, based on firefly luciferase as a reporter gene. We observed that in the absence of stimuli, each exon contained the 5'UTR of the BDNF leads to a different level of translation of the reporter gene. We therefore conducted a systematic pharmacological translation of each BDNF transcript to determine what compounds may be used to stimulate the synthesis of BDNF starting from its own specific transcripts. The treatment with serotonin and norepinephrine separately, or with two antidepressants such as desipramine and mirtazapine were found to be most effective in stimulating the BDNF synthesis. These results encourage the planning of future experiments to test the efficacy of existing antidepressant drugs in restoring the compromised BDNF levels in RTT.
La sindrome di Rett (RTT, MIM 312750) è un debilitante disordine neurologico dello sviluppo, che si manifesta nella prima infanzia e colpisce quasi esclusivamente le bambine. E’ una malattia genetica ed è presente in tutto il mondo con una incidenza media stimata di 1:10.000 / 15.000 bambine nate. La RTTè la seconda causa di ritardo mentale femminile spesso erroneamente diagnosticata come autismo o un non specificato ritardo dello sviluppo. Nella sua variante classica, questa malattia è causata da mutazioni nel fattore di trascrizione Methyl-CpG binding protein 2 (MeCP2) localizzato sul cromosoma femminile X (Amir et al., 1999). In condizioni normali MeCP2 è un regolatore della trascrizione di numerosi geni, tra cui il fattore neurotrofico Brain Derived Neurotrophic Factor (BDNF). Il BDNF è un membro della famiglia delle neurotrofine e rappresenta una molecola chiave per la sopravvivenza, lo sviluppo neuronale e i processi di apprendimento e memoria. I livelli di BDNF aumentano significativamente durante il primo periodo di vita postnatale fino a raggiungere la soglia necessaria per lo sviluppo di neuroni maturi con lo sviluppo di dendriti, assoni, spine dendritiche e sinapsi. Studi recenti hanno dimostrato che in topi transgenici in cui il gene MeCP2 è stato inattivato per mimare la sintomatologia della RTT, i livelli di mRNA del BDNF risultano ridotti e, in tali animali, a 6-8 settimane di età il contenuto totale di proteina BDNF è ridotto del 70% rispetto agli animali selvatici. Inoltre, l’overespressione di BDNF in topi privi del gene funzionale per MeCP2 porta a un aumento della durata della vita, a un miglioramento dei deficit locomotori e dei difetti elettrofisiologici, mentre la delezione del gene che codifica per bdnf negli stessi animali porta a una precoce insorgenza dei sintomi della patologia. Lo scopo di questa tesi è individuare un possibile trattamento farmacologico per la cura della RTT. L’idea si basa sul fatto che in modelli animali di RTT sono presenti dei livelli residui dell’mRNA codificante per il BDNF e che sono noti numerosi farmaci, utilizzati per lo più per la terapia della depressione che aumentano la sintesi del BDNF. In questo studio abbiamo analizzato l’espressione residuale dei diversi trascritti del BDNF in cervelli umani RTT e in due modelli di RTT. Mediante PCR quantitativa, abbiamo determinato l’espressione residuale dei trascritti del BDNF in cervelli umani di soggetti normali e affetti da RTT di età comparabile usando tessuti delle aree di Broadmann 1-5 che includono le cortecce somatosensoriali e motorie e che risultano essere le più colpite dalla malattia. Inoltre, abbiamo determinato i livelli dei trascritti del BDNF nella corteccia e nell’ippocampo di topi normali e in topi transgenici con delezione del gene MeCP2 (Bird) a differenti stadi post-natali. Infine, per stabilire un modello cellulare della malattia abbiamo distrutto l’espressione di MeCP2 nella linea cellulare di neuroblastoma umano SHSY-5Y mediante la tecnica dell’RNA interference e misurato l’espressione dei trascritti di BDNF. Utilizzando la stessa linea cellulare abbiamo ottenuto informazioni sulla traducibilità dei diversi trascritti del BDNF grazie a un saggio di luminescenza basato sull’utilizzo della luciferasi come gene reporter. Abbiamo osservato che in assenza di stimoli, ogni esone contenuto al 5’UTR del BDNF determina una diverso livello di traduzione del gene reporter. Abbiamo quindi condotto un’analisi farmacologica sistematica della traduzione di ciascun trascritto di BDNF per determinare quali composti possono essere usati per stimolare la sintesi BDNF partendo da un suo specifico trascritto. La combinazione di serotonina e norepinefrina, che si può ottenere anche mediante trattamento con antidepressivi quali desipramina e mirtazapina, è risultata essere la più efficace nello stimolare la sintesi del BDNF. Questi risultati ci incoraggiano a progettare futuri esperimenti per testare farmaci già esistenti sul mercato farmaceutico usando il modello cellulare ed il modello animale RTT.
XXIII Ciclo
1982
El, Khoury Rita. "Deux syndromes, un même gène : conséquences d'un mauvais dosage de MeCP2 sur la transmission synaptique et le comportement chez la souris." Thesis, Aix-Marseille, 2013. http://www.theses.fr/2013AIXM5075.
Повний текст джерелаMeCP2 is a multifunctional protein acting on many levels of control of genetic programs. Thus, an abnormal dosage of MeCP2 protein causes a group of neurological disorders with a common feature of severe intellectual disability. Mutations or deletions in MECP2 gene cause Rett Syndrome in females, whereas in boys its overexpression causes the MECP2-duplication Syndrome. Several mouse models of MECP2-pathologies were generated. The use of these models is crucial for understanding the mechanisms underlying the onset of symptoms related to the pathology. In our laboratory, two mouse models are under study: The Mecp2tm1Bird model with an Mecp2 deficiency and the transgenic Mecp2Tg1 model with a double expression of Mecp2. My thesis work enabled the characterization of the postnatal physiological and motor deficits affecting Mecp2Tg1 mice. My work led to a better understanding of the gene dosage effect. Our results showed that overexpression of Mecp2 in mice, led to the occurrence of motor problems, and seizures. In parallel, we studied the neural deficits affecting the GABA and the glutamate pathway in several structures of the Mecp2 deficient brain (Mecp2tm1bird). We showed that Mecp2-deficiency causes deregulation of the synaptic transmission, which is dependent on the area, and the age of the study. These deregulations underlie significant neurophysiological differences between the different regions of the brain that we still have to uncover. Furthermore, we found that pharmacological stimulation of the GABA system with Tiagabine, a molecule capable of acting on GABA transporters to prevent its uptake, increases the survival of Mecp2-deficients animals
Popescu, Andreea. "Pharmacological Rescue of Nonsense Mutations in Rett Syndrome." Thesis, 2009. http://hdl.handle.net/1807/18985.
Повний текст джерелаTsai, Wen-Hsin, and 蔡文心. "Mutation Analysis of the MECP2 Gene in Patients with Rett Syndrome and Rett-like Features." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/12546337737487678524.
Повний текст джерела國立臺灣大學
臨床醫學研究所
97
Background: Mutations in the methy-CpG-binding protein 2 (MECP2) gene are well known to cause Rett syndrome (RTT), a severe neurodevelopmental disorder, occurs almost exclusively in females, with an estimated prevalence of approximately 1 in 10,000-15,000 females. RTT is often considered an X-linked dominant condition with male lethality (Hagberg 1985) characterized by a progressive loss of intellectual function, fine gross motor skills, and communicative abilities; deceleration of head growth; and the development of stereotypic hand movements, all occurring after a period of normal development. To date, mutations have been identified in the MECP2 sequences of approximately 80-90% of all RTT; the remaining 10-20% may possess noncoding regions of this gene, or they may harbor a second RTT inducing gene or locus. Several reports have identified large gene deletions in RTT patients that escaped detection by PCR-based screening strategies (Laccone et al. 2004; Schollen et al. 2003). This study reports the result of the mutation analysis of MECP2 in 97 patients with classic or atypical RTT or RTT-like, conducted to obtain a genotypeic representation of the mutational spectrum in Taipei, Taiwan. Patients and Methods: A total of 97 clinically suspicious RTT or RTT-like patients, referred to National Taiwan University Hospital for MECP2 gene mutation analysis, were involved in this study. Patients were grouping according to the clinical diagnostic criteria for the classic or variant Rett syndrome proposed by The Rett Syndrome Diagnostic Criteria Work Group (Hagberg et al. 2002), consisting of 23 classic, 37 atypical or RTT-like, and 37 grouped into idiopathic psychomotor retardation patients.The first group composed of RTT or RTT-like patients who were fulfilled the diagnostic criteria, and this group underwent DNA direct sequencing. In the mutation-negative patient, we used multiplex ligation-dependent probe amplification (MLPA) kit P015C to screen for large deletions. The other group who weren’t fulfill the classic or atypical RTT diagnostic criteria, were considered as idiopathic psychomotor retardation, but who may be related to the MECP2-related disorders were underwent MECP2-MLPA test directly to study the possible role of MECP2 duplication in this group. Results: Mutations in MECP2 were detected in 60.1% (14/23) of the patients presenting with classic RTT, and in 8.1% (3/37) of those with atypical RTT or RTT-like features. In total, 14 different MECP2 mutations, and 1 unclassified variant or mutation were identified in 17 of the 60 diagnosed as classical or atypical RTT or RTT-like patients. Most of the variants were missense mutations, accounting for 57.1% (8/14), followed by nonsense mutations 21.4% (3/14), and frame shift mutations 21.4% (3/14). We identified five novel mutations, four of which were point mutations, and one was deletion. The first, a nonsense mutation, C>T transition at the cDNA 844 (c.844C>T), lead to CGA change to TGA and became a stop codon (p.R282X). The other three were missense mutations (p.S149Y, p.V207M, p.Q437H), and one was a 83bp deletion (c.1117_1199del83) happened in exon 4 and lead to frameshift (p.S373fs). No mutations were found in exon 1 or 2 based on our study. However, we did not pinpoint a significant relationship between genotype and phenotype in these cases. In the group of 37 patients with idiopathic psychomotor retardation, we identified one case with Xq28 duplication including MECP2 gene. Conclusion: In Taiwan, most of the screenings are PCR-based and restricted to the coding part of the gene and therefore prone to miss gene dosage changes. To our knowledge, this is the first study in Taiwan to determine the role of large deletions of the MECP2 in RTT or RTT-like patients using MLPA method. Also, it is the first study in Taiwan to determine the possible role of duplications of the MECP2 region in children with psychomotor retardation using MLPA method. Although there was no large deletion of MECP2 found in our patients with Rett or Rett-like syndrome, it remains important to screen large deletions in these patients. Because duplication of MECP2 gene remains one of the possibilities in patients with psychomotor retardation of unknown etiology, we recommend screening MECP2 gene duplications in males with moderate to severe developmental delay, especially when a history of recurrent infections has been documented. We will continue our work to screen the large deletion of MECP2 gene in RTT or RTT-like patients, and the duplication of MECP2 gene in children with psychomotor retardation of unknown etiology to clarify the role of such changes in these patients.
Bodda, Chiranjeevi. "Studying synaptopathies using Mecp2 transgenic mouse models." Thesis, 2013. http://hdl.handle.net/11858/00-1735-0000-0001-BB59-E.
Повний текст джерелаD'Cruz, Jennifer. "Alterations of Cortical and Hippocampal Network Activity in MeCP2-Deficient Mice." Thesis, 2010. http://hdl.handle.net/1807/24557.
Повний текст джерелаArunachalam, Jayamuruga Pandian. "Creation and establishment of transgenic mouse models for for Mecp2 gene, causing Rett syndrome." Doctoral thesis, 2007. http://hdl.handle.net/11858/00-1735-0000-0006-AC56-1.
Повний текст джерела"Drosophila as a Translational Model For MECP2 Gain-of-Function in Neurons." Doctoral diss., 2015. http://hdl.handle.net/2286/R.I.35984.
Повний текст джерелаDissertation/Thesis
Doctoral Dissertation Neuroscience 2015
Hirt, Ursula. "Extramitochondriale und mitochondriale Produktion reaktiver Sauerstoffspezies im Hippokampus MeCP2-defizienter Mäuse." Doctoral thesis, 2014. http://hdl.handle.net/11858/00-1735-0000-0022-5EBE-5.
Повний текст джерелаGroßer, Emanuel. "Oxidativer Stress und mitochondriale Dysfunktion in einem Mausmodell des Rett-Syndroms." Doctoral thesis, 2016. http://hdl.handle.net/11858/00-1735-0000-0028-87BF-8.
Повний текст джерелаCan, Karolina. "Redox imbalance and oxidative stress in Mecp2 deficient neurons." Doctoral thesis, 2016. http://hdl.handle.net/11858/00-1735-0000-002B-7C9D-3.
Повний текст джерелаLang, Min. "Ubiquitous Reactivation and Targeted Preservation of MeCP2 Expression in a Mouse Model of Rett Syndrome." Thesis, 2012. http://hdl.handle.net/1807/33301.
Повний текст джерелаZimmermann, Jasper Lukas. "Modulation der Hypoxie-Empfindlichkeit medullärer Netzwerke in einem Maus-Modell des Rett-Syndroms." Doctoral thesis, 2012. http://hdl.handle.net/11858/00-1735-0000-000D-F009-8.
Повний текст джерелаHein, Janine. "Quantitative Genexpressionsanalyse im respiratorischen Netzwerk an Mausmodellen für das Rett-Syndrom." Doctoral thesis, 2011. http://hdl.handle.net/11858/00-1735-0000-0006-B1BA-D.
Повний текст джерелаArunachalam, Jayamuruga Pandian [Verfasser]. "Creation and establishment of transgenic mouse models for Mecp2 gene, causing Rett syndrome / vorgelegt von Jayamuruga Pandian Arunachalam." 2007. http://d-nb.info/984666206/34.
Повний текст джерелаBebensee, Dörthe Friederike. "Analyse funktioneller und struktureller Mitochondrienveränderungen in einem Maus-Modell für das Rett-Syndrom mittels 2-Photonen-Mikroskopie." Doctoral thesis, 2017. http://hdl.handle.net/11858/00-1735-0000-002B-7CF8-8.
Повний текст джерелаFesterling, Karina. "Mitochondriale Redoxhomöostase in hippocampalen Neuronen MeCP2-defizienter Mäuse." Doctoral thesis, 2019. http://hdl.handle.net/21.11130/00-1735-0000-0003-C1B3-8.
Повний текст джерелаWegener, Jan Eike. "Charakterisierung und experimentelle Therapien eines neuen Mausmodells für das Rett Syndrom." Doctoral thesis, 2015. http://hdl.handle.net/11858/00-1735-0000-0028-8636-4.
Повний текст джерелаOginsky, Max. "Maintenance of Neuron Activity by Homeostatic Alterations in Receptors and Ion Channels in a Rett Syndrome Mouse Model." 2014. http://scholarworks.gsu.edu/biology_diss/152.
Повний текст джерелаZhong, Weiwei. "INTERVENTION TO EXTRASYNAPTIC GABAA RECEPTORS FOR SYMPTOM RELIEF IN MOUSE MODELS OF RETT SYNDROME." 2017. http://scholarworks.gsu.edu/biology_diss/186.
Повний текст джерелаFarhoomand, Farnoosh. "Sensory-evoked activity in somatosensory cortex as a model to probe cortical plasticity in a mouse model of Rett syndrome." Thesis, 2021. http://hdl.handle.net/1828/13330.
Повний текст джерелаGraduate
Wither, Robert. "MeCP2 Deficiency is Sufficient to Disrupt Daily Rhythmic Behaviours in Mice." Thesis, 2012. http://hdl.handle.net/1807/33588.
Повний текст джерелаRietveld, Leslie A. "Cell autonomous and cell non-autonomous effects of mosaic Mecp2 expression on layer V pyramidal cell morphology in a mouse model of Rett Syndrome." Thesis, 2012. http://hdl.handle.net/1828/4370.
Повний текст джерелаGraduate
Maliszewska-Cyna, Ewelina. "Examination of NMDA receptor subunit prevalence and distribution in crude synaptic membranes purified from a mouse model of Rett syndrome." Thesis, 2009. http://hdl.handle.net/1807/18983.
Повний текст джерелаFischer, Marc. "Erhöhte Hypoxieempfindlichkeit in Hippokampusschnitten bei einem Mausmodell des RETT-Syndroms." Doctoral thesis, 2012. http://hdl.handle.net/11858/00-1735-0000-000D-EFEC-F.
Повний текст джерела